Conditions: Prostate Cancer
Keywords: adenocarcinoma of the prostate stage I prostate cancer stage II prostate cancer stage III prostate cancer
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 983
Healthy volunteers: no

Brief summary:
RATIONALE: Hormones can stimulate the production of prostate cancer cells. Hormone therapy may fight prostate cancer by reducing the production of androgens. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether hormone therapy plus mitoxantrone and prednisone is more effective than hormone therapy alone for prostate cancer.

PURPOSE: This randomized phase III trial is studying hormone therapy, mitoxantrone, and prednisone to see how well they work compared to hormone therapy alone in treating patients who have undergone radical prostatectomy for prostate cancer.

Detailed description:
OBJECTIVES:

* Compare the overall and disease-free survival of patients with high-risk adenocarcinoma of the prostate treated with adjuvant androgen deprivation therapy with or without mitoxantrone and prednisone after radical prostatectomy.
* Compare the qualitative and quantitative toxic effects of these regimens in this patient population.
* Compare the prostate-specific antigen (PSA) progression-free survival rate in patient treated with these regimens.
* Determine whether PSA progression is a surrogate endpoint for survival or disease-free survival in this patient population.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to surgical extent of disease (organ confined vs not organ confined, but N0 vs N1), Gleason's sum (less than 7 vs 7 vs greater than 7), and planned radiotherapy (yes vs no). Patients are randomized to one of two treatment arms.

* Arm I:Patients receive goserelin subcutaneously once every 13 weeks (8 injections total) and oral bicalutamide once daily for 2 years in the absence of disease progression or unacceptable toxicity.
* Arm II:Patients receive mitoxantrone IV over 30 minutes on day 1 and oral prednisone twice daily on days 1-21. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive hormonal therapy as in arm I beginning concurrently with the initiation of mitoxantrone and prednisone.

Patients may undergo radiotherapy 5 days a week for 6.5-7.8 weeks beginning anytime (arm I) or after completion of chemotherapy (arm II), at the discretion of the physician, in the absence of disease progression or unacceptable toxicity.

Patients are offered the possibility to participate in biomarker research by allowing their tissue/blood to be studied.

Patients are followed every 6 months for 2 years and then annually for up to 13 years.

PROJECTED ACCRUAL: A total of 1,360 patients (680 per treatment arm) will be accrued for this study within 9.5 years.

Arms:
arm 1: androgen deprivation arm 2: androgen deprivation plus mitoxantrone, prednisone

Interventions: intervention 1: bicalutamide intervention 2: goserelin intervention 3: mitoxantrone hydrochloride intervention 4: prednisone
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None

Protocol document:
Prot_SAP_000.pdf: 
 
 
 
 
 
 
 
 
Distribution Date: 
January 15, 2015 
CTEP Submission Date:   
December 19, 2014 
 
TO: 
ALL NATIONAL CLINICAL TRIALS NETWORK (NCTN) MEMBERS 
 
FROM: 
Jennifer I. Scott, Protocol Coordinator (E-mail:  jscott@swog.org) 
 
RE: 
S9921, "Adjuvant Androgen Deprivation Versus Mitoxantrone Plus Prednisone 
Plus Androgen Deprivation in Selected High Risk Prostate Cancer Patients 
Following Radical Prostatectomy, Phase III."  Study Coordinators:  Drs. L. M. 
Glode, M.H.A. Hussain, G. P. Swanson, D. P. Wood, Jr. and W. A. Sakr. 
 
REVISION #18 
 
Study Coordinator:  L. Michael Glode, M.D.   
Phone: 303/724-3853 
E-mail:  mike.glode@uchsc.edu 
 
IRB Review Requirements 
 
(   ) 
Full board review required.  Reason: 
(   ) 
Initial activation (should your institution choose to participate) 
(   ) 
Increased risk to patient 
(   ) 
Complete study redesign 
(   ) 
Addition of tissue banking requirements 
(   ) 
Study closure due to new risk information 
 
(    ) Expedited review allowed 
 
( √ ) No review required 
 
 
REVISION #18 
 
The above-referenced protocol has been revised as follows: 
 
1. 
Pages 1 and 2a, Title Page:  The version date has been updated.  The 
participant list has been moved from Page 1 to Page 2a and revised to be 
consistent with the new NCTN/CTSU guidelines. 
 
This memorandum serves to notify the NCI and the SWOG Statistical Center. 
 
 
cc: 
PROTOCOL AND INFORMATION OFFICE 
 
Cathy M. Tangen, Dr. P.H. 
 
Melissa Plets, M.S. 
Jean Barce 
  
Austin Hamm 
Craig Silva 
 


 
 
 
 
 
Distribution Date: 
February 15, 2007 
CTEP Submission Date: 
February 1, 2007 
 
TO: 
ALL SOUTHWEST ONCOLOGY GROUP MEMBER, CCOP, AFFILIATE AND UCOP 
MEDICAL 
ONCOLOGISTS, 
RADIATION 
ONCOLOGISTS, 
SURGEONS 
AND 
PATHOLOGISTS; EPP INSTITUTIONS; CALGB; AND CTSU 
 
FROM: Jennifer I. Scott, Protocol Coordinator 
 
RE: 
S9921, "Adjuvant Androgen Deprivation Versus Mitoxantrone Plus Prednisone Plus 
Androgen Deprivation in Selected High Risk Prostate Cancer Patients Following 
Radical Prostatectomy, Phase III."  Study Coordinators:  Drs. L. M. Glode, M.H.A. 
Hussain, G. P. Swanson, D. P. Wood, Jr. and W. A. Sakr. 
 
REVISION #17 
 
Study Coordinator:  L. Michael Glode, M.D.   
Phone: 303/724-3853 
E-mail:  mike.glode@uchsc.edu 
 
IRB Review Requirements 
 
(   ) Full board review required.  Reason: 
(    ) Initial activation (should your institution choose to participate) 
(    ) Increased risk to patient 
(    ) Complete study redesign 
(    ) Addition of tissue banking requirements 
(    ) Study closure due to new risk information 
 
( √ ) Expedited review allowed 
 
(   ) No review required 
 
 
REVISION #17 
 
The above-noted protocol has been revised at the request of the Cancer Trials Support Unit 
(CTSU). 
 
The Face Page (page 2), Section 13.5 (pages 26-27), Section 14.5 (page 28a), Section 15.2 
(page 28e), Section 16.1f (page 28h), Section 19.0 (page 57), and Section 19.6 (page 65) have 
been revised to incorporate the CTSU forms tracking change to basic service for this 
protocol.  Page 27a was added to prevent extensive repagination.  The Face Page has been 
revised to reflect the current version date of the protocol and to update the Table of 
Contents page number for Section 14.0. 
 
THIS STUDY REMAINS PERMANENTLY CLOSED. 
 
Please append this notice to your copy of the protocol and insert the replacement pages noted 
above. 
 
This memorandum serves to notify the NCI, CALGB, CTSU, EPP Institutions and the Southwest 
Oncology Group Statistical Center. 
 
cc: 
PROTOCOL AND INFORMATION OFFICE 
Kendra Godfrey Barrow (CTSU) 
Cathy M. Tangen, Dr. P.H. 
Kim Mosby (EMMES) 
Bryan Goldman, M.S. 
Karen Bartels, R.N., O.C.N., M.B.A. (Astra Zeneca) 
Michael A. Hussey, M.S. 
Robyn Philip-Norton (OSI Pharmaceuticals) 
Jean Barce 
Robert B. Imani, M.D., Ph.D.  
Janice Leaman 
(OSI Pharmaceuticals)  
Monica Toth, M.S. 
Greg Friedman (Priority Healthcare) 
Brian Zeller 
Charlie Drayton (Priority Healthcare)  
John Taylor (CALGB) 
Michelle Dubois (UVI, Inc.) 
 
Operations Office 
14980 Omicron Drive•San Antonio, TX 78245-3217 • Telephone 210-677-8808 • FAX 210-677-0006 • http://swog.org 


 
 
 
 
 
Distribution Date: 
February 1, 2007 
Fax and E-mail Distribution Date:  January 15, 2007 
CTEP Submission Date: 
January 15, 2007 
 
TO: 
ALL SOUTHWEST ONCOLOGY GROUP MEMBER, CCOP, AFFILIATE AND UCOP 
MEDICAL 
ONCOLOGISTS, 
RADIATION 
ONCOLOGISTS, 
SURGEONS 
AND 
PATHOLOGISTS; EPP INSTITUTIONS; CALGB; AND CTSU 
 
FROM: Laurence H. Baker, D.O., Group Chair 
 
RE: 
S9921, "Adjuvant Androgen Deprivation Versus Mitoxantrone Plus Prednisone Plus 
Androgen Deprivation in Selected High Risk Prostate Cancer Patients Following Radical 
Prostatectomy, Phase III."  Study Coordinators:  Drs. L. M. Glode, M.H.A. Hussain, G. P. 
Swanson, D. P. Wood, Jr. and W. A. Sakr. 
 
STATUS NOTICE 
 
Study Coordinator:  L. Michael Glode, M.D.   
Phone: 303/724-3853 
E-mail:  mike.glode@uchsc.edu 
 
IRB Review Requirements 
 
(   ) 
Full board review required.  Reason: 
(    ) Initial activation (should your institution choose to participate) 
(    ) Increased risk to patient 
(    ) Complete study redesign 
(    ) Addition of tissue banking requirements 
(    ) Study closure due to new risk information 
 
( √ ) 
Expedited review allowed 
 
(   ) 
No review required 
 
 
PERMANENT CLOSURE 
 
We are distributing this memorandum to the Southwest Oncology Group, CALGB, CTSU 
and EPP investigators to notify them of the immediate closure of the above-referenced 
protocol.   
 
Prompted by Southwest Oncology Group Investigators, the Southwest Oncology Group 
Data and Safety Monitoring Committee (DSMC) conducted an interim-analysis of this study 
on January 10, 2007 and recommended closing the study to accrual due to a patient safety 
issue related to an increased incident of acute myelogenous leukemia (AML).  Three cases 
of AML have been reported among the 488 patients registered to the chemotherapy arm of 
this study, using mitoxantrone, with no cases reported on the hormone deprivation arm of 
the study.    
 
As a result of the DSMC recommendations, we are closing the protocol to recruitment 
effective January 12, 2007 and mandating no further distribution of mitoxantrone.   We are 
recommending that patients on both arms of this study continue to receive the protocol-
mandated two years of hormonal treatment, and all patients should continue to be followed 
as specified in the protocol.   
 
While clinical trials have contributed greatly to medical advancements, and the well-being of 
study participants is the integral focus in the design and implementation of clinical trials, this 
result is troubling and will be a grave source of concern for the 450+ study participants who 
were randomized to the chemotherapy arm of this study.  It is with regret that I have to share 
this information.  
 
Operations Office 
14980 Omicron Drive•San Antonio, TX 78245-3217 • Telephone 210-677-8808 • FAX 210-677-0006 • http://swog.org 


 
S9921 
 
Permanent Closure (contd.) 
 
Page 2 
 
 
 
 
 
 
 
 
 
Additional details and instructions for contacting study participants on this trial will be 
provided to the involved institutions and investigators, and a press release will be issued to 
the general public on Thursday, January 18, 2007.  You may contact any of the following for 
more details: 
  
Headquarters Office, 734/998-7140 
Dr. Laurence H. Baker, Group Chair, bakerl@umich.edu 
Dr. Bruce Redman, Executive Officer, redmanb@umich.edu 
Kati Laszlo, Administrator, Laszlo@umich.edu 
 
Operations Office, 210-450-8808 
Marjorie A. Godfrey, Administrator, mgodfrey@swog.org 
Jennifer Scott, Protocol Coordinator, jscott@swog.org 
  
Dr. 
E. 
David 
Crawford, 
Genitourinary 
Cancer 
Committee 
Chair, 
720-848-
0195, david.crawford@uchsc.edu 
  
Dr. L. Michael Glode, Study Coordinator, 303-724-3853, mike.glode@uchsc.edu 
 
This memorandum serves to notify the NCI, CALGB, CTSU, EPP Institutions and the Southwest 
Oncology Group Statistical Center. 
 
 
 
 
 
cc: 
PROTOCOL AND INFORMATION OFFICE 
Cathy M. Tangen, Dr. P.H. 
Bryan Goldman, M.S. 
Michael A. Hussey, M.S. 
Jean Barce 
Janice Leaman 
Monica Toth, M.S. 
Brian Zeller 
John Taylor (CALGB) 
Kendra Godfrey Barrow (CTSU) 
Kim Mosby (EMMES) 
Karen Bartels, R.N., O.C.N., M.B.A. (Astra Zeneca) 
Robyn Philip-Norton (OSI Pharmaceuticals) 
Robert B. Imani, M.D., Ph.D.  
(OSI Pharmaceuticals)  
Greg Friedman (Priority Healthcare) 
Charlie Drayton (Priority Healthcare)  
Michelle Dubois (UVI, Inc.) 
 
 
 
 


 
 
 
 
 
Protocol Distribution Date: 
April 15, 2006 
CTEP Submission Date: 
April 3, 2006 
 
TO: 
ALL SOUTHWEST ONCOLOGY GROUP MEMBER, CCOP, AFFILIATE AND UCOP 
MEDICAL 
ONCOLOGISTS, 
RADIATION 
ONCOLOGISTS, 
SURGEONS 
AND 
PATHOLOGISTS; EPP INSTITUTIONS; CALGB; AND CTSU 
 
FROM: Jennifer I. Scott, Protocol Coordinator 
 
RE: 
S9921, "Adjuvant Androgen Deprivation Versus Mitoxantrone Plus Prednisone Plus 
Androgen Deprivation in Selected High Risk Prostate Cancer Patients Following Radical 
Prostatectomy, Phase III."  Study Coordinators:  Drs. L. M. Glode, M.H.A. Hussain, G. P. 
Swanson, D. P. Wood, Jr. and W. A. Sakr. 
 
REVISION #16 
 
Study Coordinator:  L. Michael Glode, M.D.   
Phone: 303/724-3853 
E-mail:  mike.glode@uchsc.edu 
 
IRB Review Requirements 
 
(   ) 
Full board review required.  Reason: 
(    ) Initial activation (should your institution choose to participate) 
(    ) Increased risk to patient 
(    ) Complete study redesign 
(    ) Addition of tissue banking requirements 
(    ) Study closure due to new risk information 
 
( √ ) 
Expedited review allowed 
 
(   ) 
No review required 
 
 
REVISION #16 
 
The above-noted protocol has been revised as follows: 
 
Fast Fact Sheet:  A Protocol Fast Fact Sheet has been added to this protocol. 
 
Sections 5.5a, b, and c, page 14a:  These three sections have been revised to delete the text 
"an undetectable."  Patients must have a post-operative serum prostate specific antigen (PSA) 
less than or equal to 0.2 ng/ml as stated in these sections. 
 
Section 7.5, page 17:  The second paragraph of this section has been revised to clarify the 
timing of radiation therapy.  The following sentence has been added to the sixth paragraph of this 
section, "The NCI's IMRT guidelines can be found on the Advanced Technologies Consortium 
web site (http://atc.wustl.edu under "News," then "NCI IMRT Letter"). 
 
Section 15.3, page 28e:  This section has been revised to update the address for the CALGB 
Pathology Coordinating Office and to add information regarding submission of blood specimens 
which was inadvertently omitted in Amendment #3. 
 
Section 19.3, page 61:  The header has been revised to correctly reference "Amended 2/14/06" 
rather than "Amended 2/1/06."  Please note that the Returned Medication Packing Slip 
(Section 19.3) must be included when returning Casodex or Zoladex.  Please note that 
Casodex and Zoladex must be returned to UVI, Inc. and the address to use for returns of 
Casodex or Zoladex is noted on this form along with a phone number for questions. 
 
Please append this notice to the front of your protocol and insert the replacement pages noted 
above.  The face page reflects the current version date of the protocol. 
 
Operations Office 
14980 Omicron Drive•San Antonio, TX 78245-3217 • Telephone 210-677-8808 • FAX 210-677-0006 • http://swog.org 


 
S9921 
 
Revision #16 (contd.) 
 
Page 2 
 
 
 
 
 
 
 
 
This memorandum serves to notify the NCI, CALGB, CTSU, EPP Institutions and the Southwest 
Oncology Group Statistical Center. 
 
 
 
 
 
cc: 
PROTOCOL AND INFORMATION OFFICE 
Cathy M. Tangen, Dr. P.H. 
Bryan Goldman, M.S. 
Michael A. Hussey, M.S. 
Jean Barce 
Janice Leaman 
Monica Toth, M.S. 
Brian Zeller 
John Taylor (CALGB) 
Kendra Godfrey Barrow (CTSU) 
Kim Mosby (EMMES) 
Karen Bartels, R.N., O.C.N., M.B.A. (Astra Zeneca) 
Robyn Philip-Norton (OSI Pharmaceuticals) 
Robert B. Imani, M.D., Ph.D.  
(OSI Pharmaceuticals)  
Greg Friedman (Priority Healthcare) 
Charlie Drayton (Priority Healthcare)  
Michelle Dubois (UVI, Inc.) 
 
 
 
 


 
 
 
 
 
Protocol Distribution Date: 
March 15, 2006 
CTEP Submission Date: 
February 14, 2006 
 
TO: 
ALL SOUTHWEST ONCOLOGY GROUP MEMBER, CCOP, AFFILIATE AND 
UCOP 
MEDICAL 
ONCOLOGISTS, 
RADIATION 
ONCOLOGISTS, 
SURGEONS AND PATHOLOGISTS; EPP INSTITUTIONS; CALGB; AND 
CTSU 
 
FROM: 
Jennifer I. Scott, Protocol Coordinator 
 
RE: 
S9921, "Adjuvant Androgen Deprivation Versus Mitoxantrone Plus Prednisone 
Plus Androgen Deprivation in Selected High Risk Prostate Cancer Patients 
Following Radical Prostatectomy, Phase III."  Study Coordinators:  Drs. L. M. 
Glode, M.H.A. Hussain, G. P. Swanson, D. P. Wood, Jr. and W. A. Sakr. 
 
AMENDMENT #3 
 
Study Coordinator:  L. Michael Glode, M.D.   
Phone: 303/724-3853 
E-mail:  mike.glode@uchsc.edu 
 
IRB Review Requirements 
 
( √  ) 
Full board review required.  Reason: 
 
(    ) Initial activation (should your institution choose to participate) 
 
( √ ) Increased risk to patient 
 
(    ) Complete study redesign 
 
( √ ) Addition of tissue banking requirements 
 
(    ) Study closure due to new risk information 
 
(    ) 
Expedited review allowed 
 
(    ) 
No review required 
 
 
AMENDMENT #3 
 
The above-noted study has been amended to mandate that all patients registered on or 
after June 15, 2006 be offered the opportunity to consent for specimen banking per Section 
15.0.  Institutions must submit a copy of the IRB approval of this amendment to the 
Coalition of National Cancer Cooperative Groups (and according to each Group’s 
guidelines) by June 15, 2006 in order to accrue patients after that date.  If you have not 
submitted IRB approval of this amendment by June 15, 2006, you will not be able to 
enroll patients to this study.  Patients registered on or after June 15, 2006 must be 
consented using the version of the consent form included in this amendment.  The previous 
version of the consent form will not be accepted for new patients after that time.  If patients 
who have already been registered to this study desire to bank specimens, they will need to 
be reconsented. 
 
Additionally, the protocol has been amended to update the contact information for the 
Study Coordinators; update drug ordering information, allow clinical Stage T3 patients; 
clarify the Zoladex retreatment interval, collect PSA every three months for five years and 
then every six months until 15 years or death; and to make the protocol more consistent 
with the Southwest Oncology Group and Cancer Trials Support Unit’s current standards 
regarding registration, data forms, and data submission.  Additionally, information has been 
added regarding the Southwest Oncology Group’s On-Line Specimen Tracking system.  
Since the Group’s On-Line Specimen Tracking System tracks all specimen submissions, 
registration to SWOG-9205 is no longer necessary. 
 
Operations Office 
14980 Omicron Drive•San Antonio, TX 78245-3217 • Telephone 210-677-8808 • FAX 210-677-0006 • http://swog.org 


 
S9921 
 
Amendment #3 (contd.) 
 
Page 2 
 
 
 
 
 
 
 
 
 
Specific changes to the protocol are as follows: 
 
Face Page:  The Face Page has been revised to update the contact information for Drs. 
Glode, Hussain and Swanson.  The Table of Contents has been revised to correct 
pagination which changed as a result of this amendment.   
 
Page 2:  Contact information has been updated for Dr. Wood.  Bryan Goldman, M.S. has 
replaced James Faulkner, M.S., and his contact information has been added.  The mail box 
number has been updated for the Southwest Oncology Group Statistical Center.  Drs. Wael 
Sakr’s and Cathy Tangen’s e-mail addresses have been updated.  The CTSU contact 
information has been updated to reflect their current standardized language.  Page 2a was 
added to prevent extensive repagination and the sentences "Please refer all questions 
regarding chemotherapy treatment or dose modifications to Dr. L. Michael Glode.  For 
radiation therapy related questions, contact Dr. Gregory P. Swanson." were added. 
 
Schema, page 3:  The second line of the schema has been amended to include clinical 
stages T1-T3 versus T1-T2.  This is consistent with changes made to Section 5.1.  Line 
four has been amended to correctly cross reference Section 5.1d rather than Section 5.1c. 
 
Section 1.0, page 4:  Sections 1.3-1.4 have been added in conjunction with the mandatory 
collection of PSA noted in Section 9.0.  Section 1.5 has been added regarding biologic 
endpoints.  Section 1.6 has been added regarding banking. 
 
Section 3.1c, page 8 and 3.2c, page 10:  The "Supplier" sections have been amended to 
reflect Oncology Therapeutics Network’s name change to UVI, Inc.  The contact names 
"Fadia Alaraj" and "Mike Proctor" have been replaced with the text "the clinical customer 
service staff at UVI, Inc."  The fax number has been updated.  Two sentences have been 
added to clarify method of drug shipment and expected time for delivery. 
 
Section 3.2c, page 9:  In the "Administration" section, the text "12 weeks" has been 
replaced with "3 months (13 weeks)." 
 
Section 3.3c, page 10a:   OSI Pharmaceuticals is now providing the drug mitoxantrone.  
This is reflected in the "Supplier" section. 
 
Section 5.0, page 14:  The header section of Section 5.0 has been amended to be 
consistent with current Southwest Oncology Group guidelines.  Please note that 
submission of Section 5.0 to the Data Operations Center in Seattle is no longer required.  
Information regarding test results and dates should be recorded on the S9921 Local 
Prostate Carcinoma Prestudy (Form #23968).  Lines previously provided to indicate test 
results and dates have been removed throughout Section 5.0 [specifically from Sections 
5.1 and 5.2 (page 14); Section 5.5 (page 14a); and Sections 5.7-5.9 (page 15)]. 
 
Section 5.1, page 14:  This section has been amended to include clinical Stage T3 
patients.  All patients must also be considered operable for cure by their primary urologic 
surgeon.  The "NOTE" paragraph has been deleted as specimen submissions will be 
tracked via the Southwest Oncology Group’s On-Line Specimen Tracking System and 
registration to SWOG-9205 is not necessary. 
 
Section 5.5c, page 14a:  This section has been added regarding PSA requirements for 
patients who started hormone therapy prior to prostatectomy.  Section 5.7 has been added 
requiring that all patients registered on or after June 15, 2006 be offered the opportunity to 
consent for specimen banking per Section 15.0.  The remainder of Section 5 has been 
renumbered accordingly. 
 
Section 5.0, page 15:  The header has been amended to capture "Patients Initials (L, F, 
M) rather than "Patient’s Name". 
 
 


 
S9921 
 
Amendment #3 (contd.) 
 
Page 3 
 
 
 
 
 
 
 
 
 
Section 5.11, page 15:  This section has been added to exclude patients known to be HIV 
positive.  The remainder of the Section has been renumbered accordingly. 
 
Section 5.15, page 15:  This section has been amended to indicate that the treating 
institution’s name and ID number must be provided to the Data Operations Center in 
Seattle rather than the Statistical Center. 
 
Section 6.1a, page 16:  This section has been amended to indicate that patients will be 
stratified by pathologic stage versus surgical extent of disease.  Pathology staging has 
been added to Sections 6.1a.1-2 as clarification and "any T" to Section 6.1a.3, but the 
stratification levels remain unchanged.   
 
Section 7.0, page 16:  A paragraph has been added at the top of this section outlining 
where treatment-related questions should be directed. 
 
Section 7.3a&b, page 16a:  Sections 7.3a and 7.3b have been added to provide 
clarification regarding treatment.  The table has been amended to clarify that the LHRH 
Agonist should be repeated "q 3 months (13 weeks) x 8".  The note has been deleted from 
underneath the table and replaced with the comment that "All continuous hormonal 
treatment counts towards protocol treatment." 
 
Section 7.4, page 17:  The note section has been added to clarify that the Off Treatment 
Notice should not be submitted for patients on Arm 2 until patient is off all protocol 
treatment (including hormonal therapy). 
 
Section 7.5, page 17:  The text "can be planned with 3D conformal technique.  IMRT is 
allowed as long as boundary parameters are met." Has been added just prior to the bolded 
text "AP/PA". 
 
Section 7.7b, page 18:  The text "protocol treatment" has been replaced with "2 years of 
hormonal therapy per protocol" as clarification. 
 
Section 8.3a, page 19:  The sentence "Patients who do not recover WBC or platelet 
counts to ≤ CTC Grade 1 toxicity within 21 days should be reduced to dose level -1 for all 
subsequent cycles" has been added to this section. 
 
Section 8.4, page 20:  This section has been amended to update the phone numbers of 
the Study Coordinators. 
 
Sections 9.1 and 9.2, pages 21-22:  The "†" symbol and its corresponding footnote have 
been deleted as digital rectal exam is no longer required.  The "¥" symbol has been added 
to the PSA and Testosterone lines of the calendar as well as a corresponding footnote.  
Testosterone must be collected every six months until it reaches the institutional lower limit 
of normal (ILLN).  Follow-up requirements have been clarified in the "Ω" footnote.  "Serum 
specimen" has been amended to reflect "Blood specimens" and an "X" has been added 
under the Month 7 column.  The "π" footnote has been amended to reflect blood collection 
time points.  An "X" has been added to the CT/MRI line of Section 9.2 as it was 
inadvertently omitted. 
 
Section 10.1, page 23:  Censoring language has been added to this section. 
 
Section 10.2, page 23:  This section has been amended to indicate that disease-free 
survival is measured from the date of randomization to the date of first observation of 
"recurrence" rather than "progressive disease."  Censoring language has been added to 
this section. 
 
Section 10.4, page 23:  This section has been amended to change the title from 
"Progression" to "PSA Progression" and to also indicate "> 0.2 ng/mL" rather than "0.2 
ng/mL or greater." 
 


 
S9921 
 
Amendment #3 (contd.) 
 
Page 4 
 
 
 
 
 
 
 
 
 
Section 10.5, page 23:  This section has been added to provide a definition of PSA 
Progression-free Survival. 
 
Sections 13.2-13.3, pages 24-25:  These sections have been amended to reflect current 
Southwest Oncology Group Registration Guidelines. 
 
Section 13.5, pages 26-27:  This section has been amended to reflect current CTSU 
Registration Guidelines. 
 
Section 13.6, page 27:  This section has been amended to reflect current Southwest 
Oncology Group Guidelines regarding eligibility policies. 
 
Section 14.2, page 27:  This section has been amended to indicate that forms must be 
submitted to the Data Operations Center in Seattle rather than the Statistical Center.  The 
sentence "Alternatively, data from approved SWOG institutions may be submitted on-line 
via the Web; see Section 14.3a for details" has been added. 
 
Section 14.3, page 28:  This section has been amended to reflect current Southwest 
Oncology Group Data Submission Guidelines. 
 
Section 14.4, page 28a:  This section has been amended to indicate that CALGB 
participants should submit date to the Southwest Oncology Group Data Operations Center 
rather than the Statistical Center.  The address has been updated accordingly. 
 
Section 14.5, page 28a:  This section has been amended to reflect current CTSU Data 
Submission Guidelines. 
 
Section 14.6, page 28a:  The form number for the S9921 Local Prostate Carcinoma 
Prestudy has been amended to reflect the revised form.  Reference to the completed copy 
of Section 5.0 and the Study Specific Solid Tumor Flow Sheet have been removed from 
this section. 
 
Section 14.7, page 28a:  This section has been added and the remainder of Section 14.0 
renumbered accordingly. 
 
Sections 14.8, 14.11 and 14.12, page 28b:  The titles of these sections have been 
amended and the text within amended to reflect the revised forms to be submitted. 
 
Section 14.9 and 14.11, page 28b:  These sections have been added. 
 
Section 14.13, page 28b:  This section has been amended to reflect the revised forms to 
be submitted. 
 
Section 15.1, page 28b-e:  This section has been revised to include the Southwest 
Oncology Group Specimen Tracking System Guidelines.  Instructions regarding 
submission of material for the Southwest Oncology Group Repository previously found in 
Section 15.2 have been incorporated into Section 15.1 and this section has been expanded 
to include more details regarding specimen processing and shipment. 
 
Section 15.2, page 28e:  This section was previously numbered Section 15.4. 
 
Section 15.3, page 28e:  Section 15.3b was deleted since the Southwest Oncology Group 
Specimen Submission Form has been removed from this study.  The remainder of the 
section was renumbered accordingly. 
 


 
S9921 
 
Amendment #3 (contd.) 
 
Page 5 
 
 
 
 
 
 
 
 
 
Section 16.0, pages 28f-h:  Version 5.0 of the NCI’s AdEERS (Adverse Event Expedited 
Reporting System), released June 1, 2004, expands its capability for expedited reporting of 
serious adverse events (SAEs).  SAEs on all types of treatment studies, i.e., those using 
commercial drugs, investigational drugs, a combination of commercial and investigational 
drugs, surgery, or radiation therapy, will now be reported in AdEERS. The MedWatch form 
will no longer be used for reporting SAEs on this study.  Additionally, the format for the 
reporting guidelines has changed to conform with the suggested intergroup format.  As a 
result the reporting guidelines in Section 16.0 have been revised to reflect these changes.  
The section titled "Adverse Experiences" was deleted, Section 16.1 added, and the 
reporting guidelines for CTSU investigators updated. 
 
Section 18.0, Master Forms Set, page 32:  The Southwest Oncology Group Registration 
Form and Guidelines have been updated (Form #26636 and Code Sheet dated 12/8/04).  
The S9921 Specimen Submission Form (Form #34840) has been removed from the 
protocol as the Group’s on-line Specimen Tracking system captures this information.  The 
S9921 Local Prostate Carcinoma Prestudy has been updated (Form #23968).  The flow 
sheet has been removed from this protocol, and replaced with the S9921 Treatment Form 
(Form #38859), the S9921 Chemotherapy Treatment Form (Form # 61544) and the S9921 
Adverse Event Summary Form (Form # 27242).  References to the flow sheet have been 
replaced with the appropriate form name.  Specifically, changes regarding references to 
the flow sheet have been made to Sections 5.4 (page 14), 7.5 (page 17), 7.5a and b (page 
18), and 7.8 (page 18).  The S9921 PSA Reporting Form (Form #59255) and the S9921 
Testosterone Reporting Form (Form #25939) have been added to the protocol.  The 
standard Follow-Up Form, Off Treatment Notice, and Notice of Death have been replaced 
with the Group’s current version (Forms # 64587, 8756, and 49467 respectively.) 
 
Model Informed Consent:  The four paragraphs in the section titled "How Many People 
Will Take Part in the Study" regarding tissue banking have been removed from pages 33a 
and 34, and the Group’s standard language regarding consent for use of specimens for 
research has been added as pages 41-41b.  Since the standard consent for use of 
specimens for research contains standardized language regarding the level of consent, 
items a-c have been removed from underneath the "Signature" section of page 42.  The 
risks and benefits of banking have also been removed from page 39 since they are 
duplicative of the information now provided in the Consent Form for Use of Specimens for 
Research.  The Specimen Supplemental Sheets have been added to the protocol as pages 
43-44.  The text "12 weeks" has been replaced with "3 months" on page 35, Arm 1, 
Procedures, Goserelin Acetate and page 36, Arm 2, Procedures, Goserelin Acetate.  "Loss 
of bone mineral density" was added as a "Very Likely" risk of Arm 1 on page 37.  
"Weakness, Anemia, Increased liver enzymes (blood tests), Weight gain, and 
Osteoarthritis" have been added as "Less Likely" risks for Arm 1.  "Infection, Weight gain, 
Weight loss, Fever without infection, Shortness of breath, Nail bed changes, Mouth or lip 
sores, Sweats, Mood changes (anxiety, depression, irritability), Cough, and Heartburn" 
have been added as "Less Likely" risks for Arm 2 on page 38.  A section "Rare, but 
serious" has been added for Arm 2 and the possible risk "leukemia" has been added on 
page 39.  All risks have been put in bold text.  OSI Pharmaceuticals is supplying the 
mitoxantrone rather than Immunex and this is now reflected in the Section titled "What Are 
the Costs" (last paragraph, page 40).  Institutions must update their consent forms to 
include this information for future registrations.  Patients currently being treated on this 
study must be informed of this information in the manner determined by their local 
Institutional Review Board (IRB). 
 
Appendix, page 57:  As a result of changes made throughout the protocol, the appendices 
have been repaginated.  The Returned Medication Packing Slip has been amended to 
reference UVI, Inc. rather than Axion HealthCare Inc.  Appendix 19.4, the Novantrone Drug 
Request Form has been amended to include Charlie Drayton and Greg Friedman as 
contact personnel at Priority Healthcare rather than Avis Moss.  Their phone numbers have 
been added as well.  Section 19.5, Determination of Expedited Adverse Event Reporting 
Requirements, has been added to the protocol. 
 


 
S9921 
 
Amendment #3 (contd.) 
 
Page 6 
 
 
 
 
 
 
 
 
 
Please append this notice to your copy of the protocol and replace the changed pages as 
noted above.  Please insert the following new forms:  S9921 PSA Reporting Form (Form 
#59255), S9921 Testosterone Reporting Form (Form #25939), S9921 Treatment Form 
(Form #38859), S9921 Chemotherapy Treatment Form (Form # 61544), and S9921 
Adverse Event Summary Form (Form #27242).  Please replace the Southwest Oncology 
Group Registration Form (Form #26636 replaces Form #63220), S9921 Local Prostate 
Carcinoma Prestudy (Form #23968 replaces Form #43343), Follow-Up Form (Form 
#64587 replaces Form #4120), Off Treatment Notice (Form #8756 replaces Form #25524), 
and Notice of Death (Form #49467 replaces Form #25076) with the form numbers 
referenced.  Please remove the Study Specific Solid Tumor Flow Sheet and the S9921 
Specimen Submission Form (Form #34840).  To prevent extensive repagination of the 
entire protocol pages 25 a-b, 27a-c, 40a, and 33a have been deleted and pages 2a, 28a-h, 
38a, and 41a-b added. 
 
This memorandum serves to notify the NCI, CALGB, CTSU, EPP Institutions and the 
Southwest Oncology Group Statistical Center. 
 
 
 
cc: 
PROTOCOL AND INFORMATION OFFICE 
Cathy M. Tangen, Dr. P.H. 
Bryan Goldman, M.S. 
Mike Hussey, M.S. 
Jean Barce 
Janice Leaman 
Monica Toth, M.S. 
Brian Zeller 
John Taylor (CALGB) 
Kendra Godfrey Barrow (CTSU) 
Kim Mosby (EMMES) 
Karen Bartels, R.N., O.C.N., M.B.A. (Astra Zeneca) 
Robyn Philip-Norton (OSI Pharmaceuticals) 
Robert B. Imani, M.D., Ph.D. (OSI Pharmaceuticals) 
Greg Friedman (Priority Healthcare) 
Charlie Drayton (Priority Healthcare) 
Michelle Dubois (UVI, Inc.) 


 
 
 
 
 
June 15, 2005 
 
TO: 
ALL SOUTHWEST ONCOLOGY GROUP MEMBER, CCOP, AFFILIATE AND 
UCOP 
MEDICAL 
ONCOLOGISTS, 
RADIATION 
ONCOLOGISTS, 
SURGEONS AND PATHOLOGISTS 
 
FROM: 
Jennifer I. Scott, Protocol Coordinator 
 
RE: 
S9921, "Adjuvant Androgen Deprivation Versus Mitoxantrone Plus Prednisone 
Plus Androgen Deprivation in Selected High Risk Prostate Cancer Patients 
Following Radical Prostatectomy, Phase III."  Study Coordinators:  Drs. L. M. 
Glode, M.H.A. Hussain, G. P. Swanson, D. P. Wood, Jr. and W. A. Sakr. 
 
MEMORANDUM 
 
Study Coordinator:  L. Michael Glode, M.D.  Phone: 303/315-4757 
E-mail:  mike.glode@uchsc.edu 
 
IRB Review Requirements 
 
 (    ) 
Full board review required.  Reason: 
 
(    ) Increased risk to patient 
 
(    ) Complete study redesign 
 
(    ) Addition of tissue banking requirements 
 
(    ) Study closure due to new risk information 
 
 (     ) 
Expedited review allowed 
 
 ( √  ) 
No review required 
 
 
 
MEMORANDUM 
 
Understandably, Sanofi-Aventis is anxious to initiate an adjuvant therapy trial for high risk 
prostate cancer.  We feel it is vital that we complete S9921 and sincerely ask that you do 
not open this trial at Southwest Oncology Group institutions.  We have struggled 
successfully to keep our study open, and accrual has been improving in the past year. 
Indeed, at the present rate, it may be possible to complete accrual within 3 years. 
 
However, there are very compelling scientific reasons for completing this trial as well. 
These include: 
 
a) 
Although statistically superior to mitoxantrone/prednisone in survival, the effect in 
Tax 327 and S9916 was small (3 months). 
 
b) 
Toxicities, long and short term may well be considerably different for the two 
approaches. 
 
c) 
There are examples in breast, colon, and lung cancer trials where the “best drug” 
did not necessarily translate to the best result in the adjuvant setting. 
 
d) 
It is possible that men could benefit from combining active regimens using single 
agents (e.g. Dr. Larry Norton’s studies using sequential vs. combined therapies – 
all of which are active).  For this to occur, one would need a second regimen with 
significant activity to build on. 
 
 
Operations Office 
14980 Omicron Drive•San Antonio, TX 78245-3217 • Telephone 210-677-8808 • FAX 210-677-0006 • http://swog.org 
 


 
S9921 
 
Memorandum (contd.) 
 
Page 2 
 
 
 
 
 
 
 
 
 
 
 
 
We recognize that compensation for the two studies may be different as well.  Therefore, 
for both altruistic and scientific reasons, (and potentially at a financial disadvantage to you), 
we sincerely hope you will help us to complete the FIRST large scale prostate cancer 
adjuvant trial of the modern era, S9921, which already has a 5 year lead time advantage 
for the earliest patients entered, and could well be equally effective, less toxic, and 
potentially more cost effective than the taxotere-based adjuvant trial being launched by 
Sanofi-Aventis.  We hope to collaborate with them in looking at biomarkers that could 
eventually sub-categorize patients who would benefit more from one approach than 
another. 
 
This memorandum serves to notify the Southwest Oncology Group Statistical Center. 
 
 
 
cc: 
Cathy M. Tangen, Dr. P.H. 
Nadia Howlader, M.S. 
Bryan Goldman, M.S. 
Jean Barce 
Janice Leaman 
Jenni McNurlin 
Bryan Zeller 


 
 
 
 
 
Distribution Date: 
October 1, 2003 
CTEP Submission Date: 
September 12, 2003 
 
TO: 
ALL SOUTHWEST ONCOLOGY GROUP MEMBER, CCOP, AFFILIATE AND 
UCOP MEDICAL ONCOLOGISTS, RADIATION ONCOLOGISTS, SURGEONS 
AND PATHOLOGISTS; EPP INSTITUTIONS; CALGB; CTSU 
 
FROM: 
Jennifer I. Scott, Protocol Coordinator 
 
RE: 
S9921, "Adjuvant Androgen Deprivation Versus Mitoxantrone Plus Prednisone 
Plus Androgen Deprivation in Selected High Risk Prostate Cancer Patients 
Following Radical Prostatectomy, Phase III."  Study Coordinators:  Drs. L. M. 
Glode, M.H.A. Hussain, G. P. Swanson, D. P. Wood, Jr. and W. A. Sakr. 
 
AMENDMENT #2 
 
Study Coordinator:  L. Michael Glode, M.D.  Phone: 303/315-4757 
E-mail:  mike.glode@uchsc.edu 
 
IRB Review Requirements 
 
 (  √ ) 
Full board review required.  Reason: 
 
(    ) 
Increased risk to patient 
 
(  √ ) Complete study redesign 
 
(    ) 
Addition of tissue banking requirements 
 
(    ) 
Study closure not built into study design 
 
 (     ) 
Expedited review allowed 
 
 (     ) 
No review required 
 
 
 
AMENDMENT #2 
 
At the recommendation of the Data and Safety Monitoring Committee, the statistical section of 
the above-noted protocol has been revised to reflect the lower than anticipated accrual rate.   
 
Section 11.2, page 23:  This section has been amended to reflect that initially it was 
anticipated that 250 eligible patients would be accrued per year, but that accrual has been 
slower than expected.  The accrual period estimate has been adjusted to 9.5 years. 
 
Section 11.3, page 23:  This section has been amended to also reflect an accrual period of 
9.5 years, 4 years of follow up and a power of .92. 
 
Section 11.6, page 24:  This section has been amended to reflect that the first formal interim 
analysis will be done after 700 patients have been entered rather than 1,000 which will occur 
approximately six years after the study opens rather than four years.  The last sentence has 
been amended to reflect that the final analysis will be performed approximately fours years 
after accrual has been completed rather than five. 
 
Please append this notice to your copy of the protocol and insert the enclosed replacement 
pages.  The face page reflects the current version date of the protocol. 
 
This memorandum serves to notify the NCI, CALGB, CTSU, EPP Institutions and the 
Southwest Oncology Group Statistical Center. 
 
cc: 
PROTOCOL AND INFORMATION OFFICE Gity Nasim (EMMES) 
Cathy M. Tangen, Dr. P.H. 
Anita Nelson (CTSU) 
James Faulkner, M.S. 
Denise Ferris (Astra Zeneca) 
Jean Barce 
Robyn 
Philip-Norton 
(OSI 
Pharmaceuticals) 
Kathy Bingham 
Avis Moss (Priority Healthcare) 
Jenni McNurlin 
Mike Proctor (UintaVision) 
John Taylor (CALGB) 
 
 
Operations Office 
14980 Omicron Drive•San Antonio, TX 78245-3217 • Telephone 210-677-8808 • FAX 210-677-0006 • http://swog.org 


 
 
 
 
 
September 1, 2003 
 
TO: 
ALL SOUTHWEST ONCOLOGY GROUP MEMBER, CCOP, AFFILIATE AND 
UCOP MEDICAL ONCOLOGISTS, RADIATION ONCOLOGISTS, SURGEONS 
AND PATHOLOGISTS; EPP INSTITUTIONS; CALGB; CTSU 
 
FROM: 
Jennifer I. Scott, Protocol Coordinator 
 
RE: 
S9921, "Adjuvant Androgen Deprivation Versus Mitoxantrone Plus Prednisone 
Plus Androgen Deprivation in Selected High Risk Prostate Cancer Patients 
Following Radical Prostatectomy, Phase III."  Study Coordinators:  Drs. L. M. 
Glode, M.H.A. Hussain, G. P. Swanson, D. P. Wood, Jr. and W. A. Sakr. 
 
REVISION #15 
 
Study Coordinator:  L. Michael Glode, M.D.  Phone: 303/315-4757 
E-mail:  mike.glode@uchsc.edu 
 
IRB Review Requirements 
 
(    ) 
Full board review required.  Reason: 
 
(   ) Increased risk to patient 
 
(   ) Complete study redesign 
 
(   ) Addition of tissue banking requirements 
 
(   ) Study closure not built into study design 
 
(     ) 
Expedited review allowed 
 
(  √ ) 
No review required 
 
 
 
REVISION #15 
 
The above-noted protocol has been revised as follows: 
 
Appendix 19.4, the Novantrone Drug Request Form, has been revised to update the phone 
number for Priority Healthcare Corporation.  Avis Moss has replaced Littleton Baty as the 
contact person at Priority Healthcare Corporation. 
 
Please append this notice to your copy of the protocol and replace the face page, and the 
Novantrone Drug Request Form.  The face page reflects the current version date of the 
protocol. 
 
This memorandum serves to notify the NCI, CALGB, CTSU, EPP Institutions and the 
Southwest Oncology Group Statistical Center. 
 
cc: 
PROTOCOL AND INFORMATION OFFICE 
Cathy M. Tangen, Dr. P.H. 
James Faulkner, M.S. 
Jean Barce 
Kathy Bingham 
Jenni McNurlin 
John Taylor (CALGB) 
Gity Nasim (EMMES) 
Anita Nelson (CTSU) 
LeaAnn Longueira, R.N., C.R.S. (Astra Zeneca) 
Robyn Philip-Norton (OSI Pharmaceuticals) 
Avis Moss (Priority Healthcare) 
Mike Proctor (UintaVision) 
 
Operations Office 
14980 Omicron Drive•San Antonio, TX 78245-3217 • Telephone 210-677-8808 • FAX 210-677-0006 • http://swog.org 


 
 
 
 
 
May 15, 2003 
 
TO: 
ALL SOUTHWEST ONCOLOGY GROUP MEMBER, CCOP, AFFILIATE AND 
UCOP MEDICAL ONCOLOGISTS, RADIATION ONCOLOGISTS, SURGEONS 
AND PATHOLOGISTS; EPP INSTITUTIONS; CALGB; CTSU 
 
FROM: 
Jennifer I. Scott, Protocol Coordinator 
 
RE: 
S9921, "Adjuvant Androgen Deprivation Versus Mitoxantrone Plus Prednisone 
Plus Androgen Deprivation in Selected High Risk Prostate Cancer Patients 
Following Radical Prostatectomy, Phase III."  Study Coordinators:  Drs. L. M. 
Glode, M.H.A. Hussain, G. P. Swanson, D. P. Wood, Jr. and W. A. Sakr. 
 
REVISION #14 
 
Study Coordinator:  L. Michael Glode, M.D.  Phone: 303/315-4757 
E-mail:  mike.glode@uchsc.edu 
 
IRB Review Requirements 
 
(    ) 
Full board review required.  Reason: 
 
(   ) Increased risk to patient 
 
(   ) Complete study redesign 
 
(   ) Addition of tissue banking requirements 
 
(   ) Study closure not built into study design 
 
(  √ ) 
Expedited review allowed 
 
(     ) 
No review required 
 
 
 
REVISION #14 
 
The above-noted protocol has been revised as follows: 
 
The supplier portion of Section 3.3c and Appendix 19.4, the Novantrone Drug Request Form 
have been revised to update the fax and phone numbers for Priority Healthcare Corporation.  
Littleton Baty has replaced David Jones at Priority Healthcare Corporation. 
 
Please append this notice to your copy of the protocol and replace the face page, and pages 
10a and 56, the Novantrone Drug Request Form.  The face page reflects the current version 
date of the protocol. 
 
This memorandum serves to notify the NCI, CALGB, CTSU, EPP Institutions and the 
Southwest Oncology Group Statistical Center. 
 
cc: 
PROTOCOL AND INFORMATION OFFICE 
Cathy M. Tangen, Dr. P.H. 
James Faulkner, M.S. 
Jean Barce 
Kathy Bingham 
Lori Clark 
Jenni McNurlin 
John Taylor (CALGB) 
Gity Nasim (EMMES) 
Anita Nelson (CTSU) 
Megan Davis (Astra Zeneca) 
Robyn Philip-Norton (OSI Pharmaceuticals) 
Mike Proctor (UintaVision) 
 
Operations Office 
14980 Omicron Drive•San Antonio, TX 78245-3217 • Telephone 210-677-8808 • FAX 210-677-0006 • http://swog.org 


 
 
 
 
 
November 1, 2002 
 
TO: 
ALL SOUTHWEST ONCOLOGY GROUP MEMBER, CCOP, AFFILIATE AND 
UCOP MEDICAL ONCOLOGISTS, RADIATION ONCOLOGISTS, SURGEONS 
AND PATHOLOGISTS; EPP INSTITUTIONS; CALGB; CTSU 
 
FROM: 
Jennifer I. Scott, Protocol Coordinator 
 
RE: 
S9921, "Adjuvant Androgen Deprivation Versus Mitoxantrone Plus Prednisone 
Plus Androgen Deprivation in Selected High Risk Prostate Cancer Patients 
Following Radical Prostatectomy, Phase III."  Study Coordinators:  Drs. L. M. 
Glode, M.H.A. Hussain, G. P. Swanson, D. P. Wood, Jr. and W. A. Sakr. 
 
REVISION #13 
 
Study Coordinator:  L. Michael Glode, M.D.  Phone: 303/315-4757 
E-mail:  mike.glode@uchsc.edu 
 
IRB Review Requirements 
 
(    ) 
Full board review required.  Reason: 
 
(   ) Increased risk to patient 
 
(   ) Complete study redesign 
 
(   ) Addition of tissue banking requirements 
 
(   ) Study closure not built into study design 
 
(  √ ) 
Expedited review allowed 
 
(     ) 
No review required 
 
 
 
REVISION #13 
 
The above-noted protocol has been revised as follows: 
 
The supplier portion of Section 3.3c and Appendix 19.4, the Novantrone Drug Request Form 
have been revised to reflect that mitoxantrone must be ordered from Priority Healthcare 
Corporation. 
 
Please append this notice to your copy of the protocol and replace the face page, and pages 
10a and 56, the Novantrone Drug Request Form.  The face page reflects the current version 
date of the protocol. 
 
This memorandum serves to notify the NCI, CALGB, CTSU, EPP Institutions and the 
Southwest Oncology Group Statistical Center. 
 
cc: 
PROTOCOL AND INFORMATION OFFICE 
Cathy M. Tangen, Dr. P.H. 
James Faulkner, M.S. 
Jean Barce 
Kathy Bingham 
Lori Clark 
Jenni McNurlin 
John Taylor (CALGB) 
Gity Nasim (EMMES) 
Anita Nelson (CTSU) 
Megan Davis (Astra Zeneca) 
Rose Hesselbrock (Immunex) 
Mike Proctor (UintaVision) 
 
Operations Office 
14980 Omicron Drive•San Antonio, TX 78245-3217 • Telephone 210-677-8808 • FAX 210-677-0006 • http://swog.org 


 
 
 
 
 
August 1, 2002 
 
TO: 
ALL SOUTHWEST ONCOLOGY GROUP MEMBER, CCOP, AFFILIATE AND 
UCOP MEDICAL ONCOLOGISTS, RADIATION ONCOLOGISTS, SURGEONS 
AND PATHOLOGISTS; EPP INSTITUTIONS; CALGB; CTSU 
 
FROM: 
Jennifer I. Scott, Protocol Coordinator 
 
RE: 
S9921, "Adjuvant Androgen Deprivation Versus Mitoxantrone Plus Prednisone 
Plus Androgen Deprivation in Selected High Risk Prostate Cancer Patients 
Following Radical Prostatectomy, Phase III."  Study Coordinators:  Drs. L. M. 
Glode, M.H.A. Hussain, G. P. Swanson, D. P. Wood, Jr. and W. A. Sakr. 
 
REVISION #12 
 
Study Coordinator:  L. Michael Glode, M.D.  Phone: 303/315-4757 
E-mail:  mike.glode@uchsc.edu 
 
IRB Review Requirements 
 
(    ) 
Full board review required.  Reason: 
 
(   ) Increased risk to patient 
 
(   ) Complete study redesign 
 
(   ) Addition of tissue banking requirements 
 
(   ) Study closure not built into study design 
 
(     ) 
Expedited review allowed 
 
(  √ ) 
No review required 
 
 
 
REVISION #12 
 
The above-noted protocol has been revised as follows: 
 
• 
Face Page:  In order to be consistent with the heading of Section 6.0, the Table of 
Contents 
has 
been 
revised 
to 
indicate 
that 
Section 
6.0 
is 
Stratification 
Factors/Randomization Scheme.  The "Protocol Last Changed" date has been updated to 
8/1/02. 
• 
Page 2 has been revised to update the e-mail addresses for the biostatisticians. 
• 
Page 26, Section 14.6 and page 32, Section 18.4:  The form number for the S9921 Local 
Prostate Carcinoma Prestudy Form has been revised to be consistent with the new form 
number for this form. 
• 
The S9921 Local Prostate Carcinoma Prestudy Form has been revised to collect patient 
initials rather than name and to include a note clarifying reporting of the Gleason Score.  
The form number has been revised. 
 
Please append this notice to your copy of the protocol and replace the face page, and pages 
2, 26, 32 and the S9921 Local Prostate Carcinoma Prestudy (Form #43343).  
 
This memorandum serves to notify the NCI, CALGB, CTSU, EPP Institutions and the 
Southwest Oncology Group Statistical Center. 
 
cc: 
PROTOCOL AND INFORMATION OFFICE 
John Taylor (CALGB) 
Cathy M. Tangen, Dr. P.H. 
Gity Nasim (EMMES) 
James Faulkner, M.S. 
Anita Nelson (CTSU) 
Jean Barce 
Megan Davis (Astra Zeneca) 
Kathy Bingham 
Rose Hesselbrock (Immunex) 
Lori Clark 
Mike Proctor (UintaVision) 
 
Operations Office 
14980 Omicron Drive•San Antonio, TX 78245-3217 • Telephone 210-677-8808 • FAX 210-677-0006 • http://swog.org 


 
 
 
 
 
July 1, 2002 
 
TO: 
ALL SOUTHWEST ONCOLOGY GROUP MEMBER, CCOP, AFFILIATE AND 
UCOP 
MEDICAL 
ONCOLOGISTS, 
RADIATION 
ONCOLOGISTS, 
SURGEONS AND PATHOLOGISTS; EPP INSTITUTIONS; CALGB; CTSU 
 
FROM: 
Jennifer I. Scott, Protocol Coordinator 
 
RE: 
S9921, "Adjuvant Androgen Deprivation Versus Mitoxantrone Plus Prednisone 
Plus Androgen Deprivation in Selected High Risk Prostate Cancer Patients 
Following Radical Prostatectomy, Phase III."  Study Coordinators:  Drs. L. M. 
Glode, M.H.A. Hussain, G. P. Swanson, D. P. Wood, Jr. and W. A. Sakr. 
 
REVISION #11 
 
Study Coordinator:  L. Michael Glode, M.D.  Phone: 303/315-4757 
E-mail:  mike.glode@uchsc.edu 
 
IRB Review Requirements 
 
(    ) 
Full board review required.  Reason: 
 
(   ) Increased risk to patient 
 
(   ) Complete study redesign 
 
(   ) Addition of tissue banking requirements 
 
(   ) Study closure not built into study design 
 
(     ) 
Expedited review allowed 
 
(  √ ) 
No review required 
 
 
 
REVISION #11 
 
The above-noted protocol has been revised as follows: 
 
• 
The old Registration Form (Form #15324) has been replaced with a new Registration 
Form (Form #63220) and the Coding Guidelines have been revised to be more 
consistent with current Group standards.  The form number change is reflected in 
Section 18.2. 
 
Please append this notice to your copy of the protocol and replace the face page, and page 
32 and the Registration Form (Form #63220) and Guidelines.  The face page reflects the 
date of the current revision. 
 
This memorandum serves to notify the NCI, CALGB, CTSU, EPP Institutions and the 
Southwest Oncology Group Statistical Center. 
 
cc: 
PROTOCOL AND INFORMATION OFFICE 
Cathy M. Tangen, Dr. P.H. 
James Faulkner, M.S. 
Jean Barce 
Kathy Bingham 
Lori Clark 
John Taylor (CALGB) 
Gity Nasim (EMMES) 
Anita Nelson (CTSU) 
Megan Davis (Astra Zeneca) 
Rose Hesselbrock (Immunex) 
Mike Proctor (UintaVision) 
 
 
Operations Office 
14980 Omicron Drive•San Antonio, TX 78245-3217 • Telephone 210-677-8808 • FAX 210-677-0006 • http://swog.org 


 
 
 
 
 
April 1, 2002 
 
TO: 
ALL SOUTHWEST ONCOLOGY GROUP MEMBER, CCOP, AFFILIATE AND 
UCOP 
MEDICAL 
ONCOLOGISTS, 
RADIATION 
ONCOLOGISTS, 
SURGEONS AND PATHOLOGISTS; EPP INSTITUTIONS; CALGB; CTSU 
 
FROM: 
Jennifer I. Scott, Protocol Coordinator 
 
RE: 
S9921, "Adjuvant Androgen Deprivation Versus Mitoxantrone Plus Prednisone 
Plus Androgen Deprivation in Selected High Risk Prostate Cancer Patients 
Following Radical Prostatectomy, Phase III."  Study Coordinators:  Drs. L. M. 
Glode, M.H.A. Hussain, G. P. Swanson, D. P. Wood, Jr. and W. A. Sakr. 
 
REVISION #10 
 
Study Coordinator:  L. Michael Glode, M.D.  Phone: 303/315-4757 
E-mail:  mike.glode@uchsc.edu 
 
IRB Review Requirements 
 
 (        ) Full board review required 
 
 (   √  ) 
Expedited review allowed 
 
 (      ) 
No review required 
 
 
 
REVISION #10 
 
The above-noted protocol has been revised as follows: 
 
• 
The Face Page has been revised to correct the phone numbers for Drs. Glode and 
Hussain.  This change is also reflected in Section 8.4. 
• 
Page 2 has been revised to correct the e-mail addresses for Drs. Wood and Sakr and 
replace Tracy Glass with James Faulkner, M.S. as Secondary Statistician. 
• 
Section 5.0 has been revised to allow patients who have already started post-surgical 
hormone therapy to be eligible for S9921.  These changes are reflected in Sections 5.4 
and 5.5.  A note has been added to Section 7.3 to indicate that if hormonal therapy has 
been started prior to randomization, every effort should be made to conform with the 
LHRH agonist administration schedule that is specified in the study calendar. 
• 
Sections 13.1 - 13.3 and 14.3 have been revised to reflect current Southwest Oncology 
Group registration and data submission guidelines. 
• 
Section 13.5 has been revised to change "CTSU Enrollment Coversheet" to "CTSU 
Patient Enrollment Transmittal Form." 
 
Please append this notice to your copy of the protocol and replace the face page and 
pages 2, 14, 14a, 16, 16a, 20 and 24 - 25a - b.  Pages 14a, 16a and 25b were added to 
prevent extensive repagination. 
 
This memorandum serves to notify the NCI, CALGB, CTSU, EPP Institutions and the 
Southwest Oncology Group Statistical Center. 
 
cc: 
PROTOCOL AND INFORMATION OFFICE 
John Taylor (CALGB) 
Cathy M. Tangen, Dr. P.H. 
Gity Nasim (EMMES) 
James Faulkner, M.S. 
Anita Nelson (CTSU) 
Jean Barce 
Megan Davis (Astra Zeneca) 
Kathy Bingham 
Rose Hesselbrock (Immunex) 
Lori Clark 
Mike Proctor (UintaVision) 
 
Operations Office 
14980 Omicron Drive•San Antonio, TX 78245-3217 • Telephone 210-677-8808 • FAX 210-677-0006 • http://swog.org 


 
 
 
 
 
February 15, 2002 
 
TO: 
ALL SOUTHWEST ONCOLOGY GROUP, CCOP, AFFILIATE AND UCOP 
MEDICAL ONCOLOGISTS, RADIATION ONCOLOGISTS, SURGEONS 
AND PATHOLOGISTS; EPP INSTITUTIONS; CALGB; CTSU 
 
FROM: 
Jennifer I. Scott, Protocol Coordinator 
 
RE: 
S9921, "Adjuvant Androgen Deprivation Versus Mitoxantrone Plus 
Prednisone Plus Androgen Deprivation in Selected High Risk Prostate 
Cancer Patients Following Radical Prostatectomy, Phase III."  Study 
Coordinators:  Drs. L. M. Glode, M.H.A. Hussain, G. P. Swanson, D. P. 
Wood, Jr. and W. A. Sakr. 
 
REVISION #9 
 
Study Coordinator:  L. Michael Glode, M.D.  Phone: 303/315-8801 
E-mail:  mike.glode@uchsc.edu 
 
IRB Review Requirements 
 
(        ) 
Full board review required 
 
(      ) 
Expedited review allowed 
 
(   √ ) 
No review required 
 
 
 
REVISION #9 
 
The Eastern Cooperative Oncology Group has elected to endorse S9921.  Dr. Naomi 
Balzer-Haas has been added to the face page as ECOG Study Coordinator.  Please 
note that ECOG members will enroll patients to this trial and submit data via the 
Cancer Trials Support Unit (CTSU). 
 
Please append this notice to your copy of the protocol and replace the face page and 
page 2.  The face page reflects the date of the current revision. 
 
This memorandum serves to notify the NCI, CALGB, CTSU, EPP Institutions and the 
Southwest Oncology Group Statistical Center. 
 
cc: 
PROTOCOL AND INFORMATION OFFICE 
Cathy M. Tangen, Dr. P.H. 
James Faulkner, M.S. 
Jean Barce 
Kathy Bingham 
Lori Clark 
Rodney Sutter 
Tamra Oner 
John Taylor (CALGB) 
Gity Nasim (EMMES) 
Anita Nelson (CTSU) 
Megan Davis (Astra Zeneca) 
Rose Hesselbrock (Immunex) 
Mike Proctor (UintaVision) 
 
Operations Office 
14980 Omicron Drive•San Antonio, TX 78245-3217 • Telephone 210-677-8808 • FAX 210-677-0006 • http://swog.org 


 
 
 
 
 
December 15, 2001 
 
TO: 
ALL SOUTHWEST ONCOLOGY GROUP, CCOP, AFFILIATE AND UCOP 
MEDICAL ONCOLOGISTS, RADIATION ONCOLOGISTS, SURGEONS 
AND PATHOLOGISTS; EPP INSTITUTIONS; CALGB; CTSU 
 
FROM: 
Jennifer I. Scott, Protocol Coordinator 
 
RE: 
S9921, "Adjuvant Androgen Deprivation Versus Mitoxantrone Plus 
Prednisone Plus Androgen Deprivation in Selected High Risk Prostate 
Cancer Patients Following Radical Prostatectomy, Phase III."  Study 
Coordinators:  Drs. L. M. Glode, M.H.A. Hussain, G. P. Swanson, D. P. 
Wood, Jr. and W. A. Sakr. 
 
MEMORANDUM 
 
Study Coordinator:  L. Michael Glode, M.D.  Phone: 303/315-8801 
E-mail:  mike.glode@uchsc.edu 
 
IRB Review Requirements 
 
(        ) 
Full board review required 
 
(      ) 
Expedited review allowed 
 
(   √ ) 
No review required 
 
 
 
MEMORANDUM 
 
Immunex has notified the Southwest Oncology Group that they will be closed at the 
end of the business day on Friday, December 21, 2001 through Tuesday, January 1, 
2002 and will reopen on Wednesday, January 2, 2002.  During this period, Immunex 
will not ship study drug (mitoxantrone). 
 
ORDERING DRUG 
 
To prepare for the holiday close, Immunex asks that you check with your 
investigational pharmacist to assure that there will be an adequate supply of 
mitoxantrone during this time.  If you need additional drug, please have the pharmacist 
order drug no later than 10:00 AM Pacific time on Monday, December 17, 2001.  This 
will allow Immunex to ship the drug and confirm its arrival before the holiday break. 
 
Please append this notice to your copy of the protocol. 
 
This memorandum serves to notify the NCI, CALGB, CTSU, EPP Institutions and the 
Southwest Oncology Group Statistical Center. 
 
cc: 
PROTOCOL AND INFORMATION OFFICE 
John Taylor (CALGB) 
Cathy M. Tangen, Dr. P.H. 
Gity Nasim (EMMES) 
James Faulkner, M.S. 
Anita Nelson (CTSU) 
Jean Barce 
Megan Davis (Astra Zeneca) 
Kathy Bingham 
Rose Hesselbrock (Immunex) 
Lori Clark 
Mike Proctor (UintaVision) 
Rodney Sutter 
 
Tamra Oner 
 
 
Operations Office 
14980 Omicron Drive•San Antonio, TX 78245-3217 • Telephone 210-677-8808 • FAX 210-677-0006 • http://swog.org 


 
 
 
 
 
July 15, 2001 
 
TO: 
ALL SOUTHWEST ONCOLOGY GROUP, CCOP, AFFILIATE AND UCOP 
MEDICAL ONCOLOGISTS, RADIATION ONCOLOGISTS, SURGEONS 
AND PATHOLOGISTS; EPP INSTITUTIONS; CALGB; CTSU 
 
FROM: 
Jennifer I. Scott, Protocol Coordinator 
 
RE: 
S9921, "Adjuvant Androgen Deprivation Versus Mitoxantrone Plus 
Prednisone Plus Androgen Deprivation in Selected High Risk Prostate 
Cancer Patients Following Radical Prostatectomy, Phase III."  Study 
Coordinators:  Drs. L. M. Glode, M.H.A. Hussain, G. P. Swanson, D. P. 
Wood, Jr. and W. A. Sakr. 
 
REVISION #8 
 
Study Coordinator:  L. Michael Glode, M.D.  Phone: 303/315-8801 
E-mail:  mike.glode@uchsc.edu 
 
IRB Review Requirements 
 
(        ) 
Full board review required 
 
(   √ ) 
Expedited review allowed 
 
(     ) 
No review required 
 
 
 
REVISION #8 
 
The Immunex Drug Distribution fax number has changed.  The revised number is 
reflected under "supplier" on page 10a and on the Novantrone Drug Request Form 
(Appendix 19.4). 
 
Please append this notice to your copy of the protocol and replace the face page and 
pages 10a  and 56.  The face page reflects the date of the current revision. 
 
This memorandum serves to notify the NCI, CALGB, CTSU, EPP Institutions and the 
Southwest Oncology Group Statistical Center. 
 
cc: 
PROTOCOL AND INFORMATION OFFICE 
Cathy M. Tangen, Dr. P.H. 
Tracy R. Glass, M.S. 
Kathy Bingham 
Rodney Sutter 
Jean Barce 
Lori Clark 
Nickey McCasland, R.N. 
John Taylor (CALGB) 
Gity Nasim (EMMES) 
Anita Nelson (CTSU) 
Megan Davis (Astra Zeneca) 
Rose Hesselbrock (Immunex) 
Mike Proctor (Uinta Vision) 
 
Operations Office 
14980 Omicron Drive•San Antonio, TX 78245-3217 • Telephone 210-677-8808 • FAX 210-677-0006 • http://swog.org 


 
 
 
 
 
 
July 1, 2001 
 
TO: 
ALL SOUTHWEST ONCOLOGY GROUP, CCOP, AFFILIATE AND UCOP 
MEDICAL ONCOLOGISTS, RADIATION ONCOLOGISTS, SURGEONS 
AND PATHOLOGISTS; EPP INSTITUTIONS; CALGB; CTSU 
 
FROM: 
Jennifer I. Scott, Protocol Coordinator 
 
RE: 
S9921, "Adjuvant Androgen Deprivation Versus Mitoxantrone Plus 
Prednisone Plus Androgen Deprivation in Selected High Risk Prostate 
Cancer Patients Following Radical Prostatectomy, Phase III."  Study 
Coordinators:  Drs. L. M. Glode, M.H.A. Hussain, G. P. Swanson, D. P. 
Wood, Jr. and W. A. Sakr. 
 
REVISION #7 
 
Study Coordinator:  L. Michael Glode, M.D.  Phone: 303/315-8801 
E-mail:  mike.glode@uchsc.edu 
 
IRB Review Requirements 
 
(        ) 
Full board review required 
 
(   √ ) 
Expedited review allowed 
 
(     ) 
No review required 
 
 
 
REVISION #7 
 
The above noted protocol has been revised as follows: 
 
• 
The heading of Section 5.0 has been revised to indicate that this section must 
be photocopied, completed and submitted as part of the initial forms set.  
Section 14.6 has been revised to include a completed copy of Section 5.0 as 
part of the initial forms set. 
 
• 
Section 5.1c has been revised to remove the verbiage "and pT3a (extra-
prostatic extension)" since it is felt that all patients with a pathologic Gleason's 
sum of 7 and positive margins are at high risk.  Section 5.1d has been revised 
to remove "have received preoperative hormone therapy" to expand the criteria 
to allow patients with similar features regardless of preoperative hormone 
therapy status.  The following statement has been added to Section 5.4:  "The 
use of low dose megace (< 40 mg/day) for the treatment of hot flashes is 
allowed."  Section 5.5 has been revised to clarify that PSA must be less than or 
equal to 0.2 ng/ml. 
 
• 
In keeping with standard medical practice, Section 7.4b and the Study 
Calendar have been revised to indicate that prednisone treatment should be 
tapered at the discretion of the treating physician. 
 
• 
The Study Calendar has been revised to clarify that follow up MUGAs or 2-d 
echos are only needed for those patients who required one at baseline. 
 
 
Operations Office 
14980 Omicron Drive•San Antonio, TX 78245-3217 • Telephone 210-677-8808 • FAX 210-677-0006 • http://swog.org 


 
S9921 
 
Revision #7 (contd.) 
 
Page 2 
 
 
 
 
 
 
 
 
 
 
 
 
• 
CALGB institutions participating on Southwest Oncology Group-coordinated 
studies will now submit data directly to the Southwest Oncology Group 
Statistical Center rather than routing it through the CALGB Data Management 
Center.  Data submission instructions for CALGB institutions have been 
revised in Section 14.4. 
 
• 
The heading "FOR CTSU INVESTIGATORS ONLY" which appears on the first 
page of the model informed consent has been replaced with the following text, 
"It is suggested that CTSU institutions incorporate the following paragraph in 
their consent form."  The section of the model informed consent that addresses 
the level of patient’s consent regarding additional use of specimens has been 
put in bolded text.  This was inadvertently not done at the time the protocol was 
distributed. 
 
As a reminder, for those patients randomized to the mitoxantrone arm, mitoxantrone 
will be supplied and distributed by Immunex for this study.  Mitoxantrone should be 
requested by faxing an S9921 Novantrone ® Drug Request Form (see Section 19.4) to 
the Immunex Drug Distribution Center (see Section 3.3.c).  Drug will be shipped 
Monday through Wednesday and a minimum of two days notice is required. 
 
Please append this notice to your copy of the protocol and replace the face page and 
pages 14, 17, 22, 25a, 26, 33 and 42.  The face page reflects the date of the current 
revision. 
 
This memorandum serves to notify the NCI, CALGB, CTSU, EPP Institutions and the 
Southwest Oncology Group Statistical Center. 
 
cc: 
PROTOCOL AND INFORMATION OFFICE 
Cathy M. Tangen, Dr. P.H. 
Tracy R. Glass, M.S. 
Kathy Bingham 
Rodney Sutter 
Jean Barce 
Lori Clark 
Nickey McCasland, R.N. 
John Taylor (CALGB) 
Gity Nasim (EMMES) 
Anita Nelson (CTSU) 
Megan Davis (Astra Zeneca) 
Rose Hesselbrock (Immunex) 
Mike Proctor (Uinta Vision) 


 
 
 
 
 
February 1, 2001 
 
TO: 
ALL SOUTHWEST ONCOLOGY GROUP, CCOP, AFFILIATE AND UCOP 
MEDICAL ONCOLOGISTS, RADIATION ONCOLOGISTS, SURGEONS 
AND PATHOLOGISTS; EPP INSTITUTIONS; CALGB; CTSU 
 
FROM: 
Jennifer I. Scott, Protocol Coordinator 
 
RE: 
S9921, "Adjuvant Androgen Deprivation Versus Mitoxantrone Plus 
Prednisone Plus Androgen Deprivation in Selected High Risk Prostate 
Cancer Patients Following Radical Prostatectomy, Phase III."  Study 
Coordinators:  Drs. L. M. Glode, M.H.A. Hussain, G. P. Swanson, D. P. 
Wood, Jr. and W. A. Sakr. 
 
REVISION #6 
 
Study Coordinator:  L. Michael Glode, M.D.  Phone: 303/315-8801 
E-mail:  mike.glode@uchsc.edu 
 
IRB Review Requirements 
 
(        ) 
Full board review required 
 
(   √ ) 
Expedited review allowed 
 
(     ) 
No review required 
 
 
 
REVISION #6 
 
Attached please find a copy of a brochure prepared by the Study Coordinator for your 
use as a recruitment tool for the above noted study. 
 
Also please note that section 3.3 c of the above noted protocol has been revised under 
"Formulation" to indicate that only the 12.5 ml vial will be supplied for this study. 
 
Please append this notice to your copy of the protocol and replace the face page and 
page 10a.  The face page reflects the date of the current revision. 
 
This memorandum serves to notify the NCI, CALGB, CTSU, EPP Institutions and the 
Southwest Oncology Group Statistical Center. 
 
cc: 
PROTOCOL AND INFORMATION OFFICE 
Cathy M. Tangen, Dr. P.H. 
Tracy R. Glass, M.S. 
Kathy Bingham 
Rodney Sutter 
Jean Barce 
Lori Clark 
Nickey McCasland, R.N. 
John Taylor (CALGB) 
Gity Nasim (EMMES) 
Anita Nelson (CTSU) 
Megan Davis (Astra Zeneca) 
Rose Hesselbrock (Immunex) 
Mike Proctor (OTN) 
 
Operations Office 
14980 Omicron Drive•San Antonio, TX 78245-3217 • Telephone 210-677-8808 • FAX 210-677-0006 • http://swog.org 


Improving the OUTCOME for
High Risk Prostate Cancer Patients
THE PROBLEM
1. Prostate cancer patients do well
after surgery IF their pathology is
favorable.
2. High Risk patients are usually not
cured by surgery alone.
3. For breast cancer, hormonal and
chemotherapy adds significantly to
survival.
THE SOLUTION
Both Urologists and Patients should
discuss the final pathology results,
considering the risk factors for relapse.
High Risk means having one or more of
the following:
♦ Gleason Sum ≥ 8
♦ Positive lymph nodes
♦ Positive surgical margin
♦ Positive seminal vesicles
If one or more of these conditions exist,
consider participating in the S9921
Clinical Trial
SOUTHWEST ONCOLOGY GROUP
14980 Omicron Drive
San Antonio, TX 78245-3217
(210) 677-8808
(210) 677-0006
Treating High Risk Patients
After Surgery
NOW WE ALL CAN
DO MORE!
This figure shows the 
 among 19 patients
in each arm of a clinical trial
comparing hormone treatment to
hormone treatment plus
chemotherapy. None of these
patients had surgery on the
prostate. Also, none of them had
positive bone or CT scans. The
question is whether such treatment
would work 
. Reference: BJU
International (2000), 86:675-689
Hormones
+ chemo
Hormones
alone?


ABOUT CLINICAL
TRIALS
clinical trial is a research study to
answer specific questions about
vaccines, new therapies, or new
ways of using standard treatments.
Clinical trials (also called medical
research and research studies) are used to
determine whether new drugs or
treatments are both safe and effective.
Carefully conducted clinical trials are the
safest and most efficient way to find
treatments that work. Unlike other fields,
placebo-controlled trials in cancer
research are rare and are used only if
there is no known treatment available.
All  patients on the    
S9921
   
Clinical Trial receive
additional hormone therapy.
This will consist of Zoladex
and Casodex, two drugs that
reduce the effect of
testosterone on any cancer
cells remaining in the body.
In addition,    
half
  of the
patients receive Prednisone
and Mitoxantrone, two drugs
known to be effective in
killing additional prostate
cancer cells. Prednisone is a
hormone, and Mitoxantrone
is a chemotherapy drug.
WHY DOESN'
T EVERYONE GET
ALL OF THE DRUGS?
 It is unknown whether additional
chemotherapy plus prednisone will be
helpful after surgery, and there are side
effects of chemotherapy. The figure on
the front of this brochure compared
hormone treatment alone to hormones
plus chemotherapy in a very limited
number of patients (19 per group). None
of these patients had surgery on the
prostate, and none had any evidence of
metastases. S9921 compares the two
treatment methods in patients after
surgery.
HOW WILL MY TREATMENT BE
DETERMINED?
 If you and your doctor find that you
are eligible for the study, you will be
asked to sign a detailed consent form that
explains all the risks and benefits of
participating in the trial. You would then
start either the hormone only
(Zoladex/Casodex) treatment OR the
same treatment plus the
Prednisone/Mitoxantrone. A computer
will randomize patients onto the two arms
of the study.
WHO WILL BE IN CHARGE?
Your urologist will work closely with
other cancer specialists in caring for you.
Some patients may receive additional
treatment with radiation therapy to the
prostate bed if the doctors feel this would
be best for controlling local disease. A
medical oncologist will most likely be the
person directing the chemotherapy. Many
times, this type of "team approach" can
result in the best of care.
HOW CAN I L
EARN MORE
ABOUT THIS TRIAL?
A consent form is available for you to read which
explains the risks and benefits of participating in
this trial. Simply ask your doctor for a copy.
WHAT OTHER TREATMENTS
ARE AVAILABLE?
For patients with high risk prostate cancer, no further
therapy has been the standard of care until very
recently. Many physician experts in the field now feel
that hormone treatment such as is given to ALL
patients in this trial will improve survival. Radiation
therapy to the prostate bed is another consideration,
since it can kill cells which might have been left
behind. Its overall impact on survival is less clear,
and like chemotherapy, it produces some side effects.
Ongoing research on vaccines, gene therapy, anti-
angiogenesis, and novel hormonal treatments are
sometimes considered in cases of high risk prostate
cancer, but none of these are considered standard and
none have been proven to improve outcomes.
WHERE CAN I L
EARN MORE?
There are many useful books written
for prostate cancer patients and
brochures
 are available from
 the
National Cancer Institute. For general
questions, call 1-800-4-Cancer or visit
the
 National
 Cancer
 Institute
 Website
(www.nci.nih.org).  Additional
information
 is
 available
 from
 the
American
 Cancer
 Society
(www.cancer.org), the American
Society
 of
 Clinical
 Oncology
(www.asco.org) and
 the
 American
Urologic Association
(www.auanet.org).
A


 
 
 
 
 
 
January 1, 2001 
 
TO: 
ALL SOUTHWEST ONCOLOGY GROUP, CCOP, AFFILIATE AND UCOP 
MEDICAL ONCOLOGISTS, RADIATION ONCOLOGISTS, SURGEONS 
AND PATHOLOGISTS; EPP INSTITUTIONS; CALGB; CTSU 
 
FROM: 
Jennifer I. Scott, Protocol Coordinator 
 
RE: 
S9921, "Adjuvant Androgen Deprivation Versus Mitoxantrone Plus 
Prednisone Plus Androgen Deprivation in Selected High Risk Prostate 
Cancer Patients Following Radical Prostatectomy, Phase III."  Study 
Coordinators:  Drs. L. M. Glode, M.H.A. Hussain, G. P. Swanson, D. P. 
Wood, Jr. and W. A. Sakr. 
 
REVISION #5 
 
Study Coordinator:  L. Michael Glode, M.D.  Phone: 303/315-8801 
E-mail:  mike.glode@uchsc.edu 
 
IRB Review Requirements 
 
( √  ) 
Full board review required 
 
(     ) 
Expedited review allowed 
 
(     ) 
No review required 
 
 
 
REVISION #5 
 
The above-noted protocol has been revised as follows: 
 
The Table of Contents has been revised to correct the page numbers indicated for the 
Data Submission Schedule, Special Instructions and Ethical and Regulatory 
Considerations. 
 
Section 5.4 has been revised to clarify that patients must not have received prior 
radiation therapy.  If the treating physician wishes to have RT administered, then the 
patient should be registered to the study FIRST and then optional RT can be given on 
protocol.  All RT should be documented on the flow sheet. 
 
Section 7.5 has been revised to correctly indicate that radiation therapy for patients on 
either arm of the study will be allowed at the physician's discretion following the 
guidelines outlined in this section.  This applies to all patients, not just those with positive 
surgical margins. 
 
Section 9.2, the study calendar for arm 2, has been corrected as follows:  the "x"s have 
been deleted under Month 4 for mitoxantrone and prednisone; "x"s have been added for 
bicalutamide since it is taken daily; and "x"s have been moved from Month 4 to Day 106 
(Cycle 6) for history and physical exam and weight and performance status. 
 
 
 
 
 
Operations Office 
14980 Omicron Drive•San Antonio, TX 78245-3217 • Telephone 210-677-8808 • FAX 210-677-0006 • http://swog.org 


 
S9921 
 
Revision #5 (contd.) 
 
Page 2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Attached please find a report of an adverse event submitted to the Food and Drug 
Administration (FDA) by AstraZeneca.  The decision to amend the local consent form 
should be made by the local institutional review board. 
 
Please append this notice to your copy of the protocol and replace the face page and 
pages 14, 17 and 22.  The face page reflects the date of the current revision. 
 
This memorandum serves to notify the NCI, CALGB, CTSU, EPP Institutions and the 
Southwest Oncology Group Statistical Center. 
 
cc: 
PROTOCOL AND INFORMATION OFFICE 
Cathy M. Tangen, Dr. P.H. 
Tracy R. Glass, M.S. 
Kathy Bingham 
Rodney Sutter 
Jean Barce 
Lori Clark 
Nickey McCasland, R.N. 
John Taylor (CALGB) 
Gity Nasim (EMMES) 
Anita Nelson (CTSU) 
Megan Davis (Astra Zeneca) 
Rose Hesselbrock (Immunex) 
Mike Proctor (OTN) 
 
 
 






 
 
 
 
 
Faxed: 
December 15, 2000 
Mailed: 
January 1, 2001 
 
TO: 
ALL SOUTHWEST ONCOLOGY GROUP, CCOP, AFFILIATE AND UCOP 
MEDICAL ONCOLOGISTS, RADIATION ONCOLOGISTS, SURGEONS 
AND PATHOLOGISTS; EPP INSTITUTIONS; CALGB; CTSU 
 
FROM: 
Jennifer I. Scott, Protocol Coordinator 
 
RE: 
S9921, "Adjuvant Androgen Deprivation Versus Mitoxantrone Plus 
Prednisone Plus Androgen Deprivation in Selected High Risk Prostate 
Cancer Patients Following Radical Prostatectomy, Phase III."  Study 
Coordinators:  Drs. L. M. Glode, M.H.A. Hussain, G. P. Swanson, D. P. 
Wood, Jr. and W. A. Sakr. 
 
MEMORANDUM 
 
Study Coordinator:  L. Michael Glode, M.D.  Phone: 303/315-8801 
E-mail:  mike.glode@uchsc.edu 
 
IRB Review Requirements 
 
(    ) 
Full board review required 
 
(    ) 
Expedited review allowed 
 
( √  ) 
No review required 
 
 
 
MEMORANDUM 
 
Immunex has notified the Southwest Oncology Group that they will be closed at the end 
of the business day on Thursday, December 21, 2000 through Monday, January 1, 2001 
and will reopen on Tuesday, January 2, 2001.  During this period, Immunex will not ship 
study drug (mitoxantrone). 
 
ORDERING DRUG 
 
To prepare for the holiday close, Immunex asks that you check with your investigational 
pharmacist to assure that there will be an adequate supply of mitoxantrone during this 
time.  If you need additional drug, please have the pharmacist order drug no later than 
10:00 AM Pacific time on Tuesday, December 19, 2000.  This will allow Immunex to ship 
the drug and confirm its arrival before the holiday break. 
 
Please append this notice to your copy of the protocol. 
 
This memorandum serves to notify the NCI and the Southwest Oncology Group 
Statistical Center. 
 
cc: 
PROTOCOL AND INFORMATION OFFICE 
John Taylor (CALGB) 
Cathy M. Tangen, Dr. P.H. 
Gity Nasim (EMMES) 
Tracy R. Glass, M.S. 
Anita Nelson (CTSU) 
Kathy Bingham 
Megan Davis (Astra Zeneca) 
Rodney Sutter 
Rose Hesselbrock (Immunex) 
Jean Barce 
Mike Proctor (OTN) 
Lori Clark 
 
Operations Office 
14980 Omicron Drive•San Antonio, TX 78245-3217 • Telephone 210-677-8808 • FAX 210-677-0006 • http://swog.org 


 
 
 
 
 
July 15, 2000 
 
TO: 
ALL SOUTHWEST ONCOLOGY GROUP, CCOP, AFFILIATE AND UCOP 
MEDICAL ONCOLOGISTS, RADIATION ONCOLOGISTS, SURGEONS 
AND PATHOLOGISTS; EPP INSTITUTIONS; CALGB; CTSU 
 
FROM: 
Jennifer Scott Gazvoda, Protocol Coordinator 
 
RE: 
S9921, "Adjuvant Androgen Deprivation Versus Mitoxantrone Plus 
Prednisone Plus Androgen Deprivation in Selected High Risk Prostate 
Cancer Patients Following Radical Prostatectomy, Phase III."  Study 
Coordinators:  Drs. L. M. Glode, M.H.A. Hussain, G. P. Swanson, D. P. 
Wood, Jr. and W. A. Sakr. 
 
REVISION #4 
 
Study Coordinator:  L. Michael Glode, M.D.  Phone: 303/315-8801 
E-mail:  mike.glode@uchsc.edu 
 
 
IRB Review Requirements 
 
(    ) 
Full board review required 
 
( √ ) 
Expedited review allowed 
 
(    ) 
No review required 
 
 
 
REVISION #4 
 
The above-noted protocol has been revised as follows: 
 
Section 13.1 has been revised to indicate that patients must be registered prior to 
initiation of treatment (no more than ten working days prior to planned start of treatment).  
The additional time is to allow for the ordering and shipment of mitoxantrone for patients 
randomized to Arm 2. 
 
Please append this notice to your copy of the protocol and replace page 24. 
 
This memorandum serves to notify the NCI and the Southwest Oncology Group 
Statistical Center. 
 
cc: 
PROTOCOL AND INFORMATION OFFICE 
Cathy M. Tangen, Dr. P.H. 
Tracy R. Glass, M.S. 
Kathy Bingham 
Rodney Sutter 
Jean Barce 
John Taylor (CALGB) 
Gity Nasim (EMMES) 
Anita Nelson (CTSU) 
Megan Davis (Astra Zeneca) 
Rose Hesselbrock (Immunex) 
Mike Proctor (OTN) 
 
Operations Office 
14980 Omicron Drive•San Antonio, TX 78245-3217 • Telephone 210-677-8808 • FAX 210-677-0006 • http://swog.org 


 
 
 
 
 
July 1, 2000 
 
TO: 
ALL SOUTHWEST ONCOLOGY GROUP, CCOP, AFFILIATE AND UCOP 
MEDICAL ONCOLOGISTS, RADIATION ONCOLOGISTS, SURGEONS AND 
PATHOLOGISTS; EPP INSTITUTIONS; CALGB; CTSU 
 
FROM: 
Jennifer Scott Gazvoda, Protocol Coordinator 
 
RE: 
S9921, "Adjuvant Androgen Deprivation Versus Mitoxantrone Plus Prednisone 
Plus Androgen Deprivation in Selected High Risk Prostate Cancer Patients 
Following Radical Prostatectomy, Phase III."  Study Coordinators:  Drs. L. M. 
Glode, M.H.A. Hussain, G. P. Swanson, D. P. Wood, Jr. and W. A. Sakr. 
 
AMENDMENT #1 
 
Study Coordinator:  L. Michael Glode, M.D.  Phone: 303/315-8801 
E-mail:  mike.glode@uchsc.edu 
 
IRB Review Requirements 
 
( √ ) 
Full board review required 
 
(     ) Expedited review allowed 
 
(     ) No review required 
 
 
 
AMENDMENT #1 
 
The above-noted protocol has been amended as follows: 
 
Section 1.1b has been amended to read "mitoxantrone + prednisone administered with 
Casodex®  + Zoladex®" to be consistent with the treatment section of the protocol. 
 
The area code for the Immunex Drug Distribution Center has been changed to 425.  This 
change is reflected in Section 3.3c and Appendix 19.4. 
 
Currently, patients with a history of neoadjuvant hormones are eligible for this study.  The 
following has been added as Section 5.1d to allow for patients who have cT1-2 and are 
considered high risk:  "Patients who have received preoperative hormone therapy and have 
either a preoperative serum PSA value of > 15 ng/ml, or a biopsy Gleason score > 7, or a 
serum PSA level of > 10 ng/ml and a biopsy Gleason score > 6 are eligible."   
 
Please append this notice to your copy of the protocol and replace pages 4, 10a, 14 - 15 and 
56. 
 
This memorandum serves to notify the NCI and the Southwest Oncology Group Statistical 
Center. 
 
cc: 
PROTOCOL AND INFORMATION OFFICE 
John Taylor (CALGB) 
Cathy M. Tangen, Dr. P.H. 
Gity Nasim (EMMES) 
Tracy R. Glass, M.S. 
Anita Nelson (CTSU) 
Kathy Bingham 
Megan Davis (Astra Zeneca) 
Rodney Sutter 
Rose Hesselbrock (Immunex) 
Jean Barce 
Mike Proctor (OTN) 
 
Operations Office 
14980 Omicron Drive•San Antonio, TX 78245-3217 • Telephone 210-677-8808 • FAX 210-677-0006 • http://swog.org 


 
 
 
 
 
June 1, 2000 
 
TO: 
ALL SOUTHWEST ONCOLOGY GROUP, CCOP, AFFILIATE AND UCOP 
MEDICAL ONCOLOGISTS, RADIATION ONCOLOGISTS, SURGEONS 
AND PATHOLOGISTS; EPP INSTITUTIONS; CALGB; CTSU 
 
FROM: 
Jennifer Scott Gazvoda, Protocol Coordinator 
 
RE: 
S9921, "Adjuvant Androgen Deprivation Versus Mitoxantrone Plus 
Prednisone Plus Androgen Deprivation in Selected High Risk Prostate 
Cancer Patients Following Radical Prostatectomy, Phase III."  Study 
Coordinators:  Drs. L. M. Glode, M.H.A. Hussain, G. P. Swanson, D. P. 
Wood, Jr. and W. A. Sakr. 
 
REVISION #3 
 
Study Coordinator:  L. Michael Glode, M.D.  Phone: 303/315-8801 
E-mail:  mike.glode@uchsc.edu 
 
 
 
REVISION #3 
 
The above-noted protocol has been revised as follows: 
 
1. 
The Cancer Trials Support Unit (CTSU) has been added as a participant in this 
study.  The logistics for CTSU are reflected in the Title Page (Pages 1 and 2), 
Section 13.5 (Registration Guidelines), Section 14.5 (Data Submission 
Schedule), Section 16.0 (Adverse Event Reporting) and the Informed Consent 
Document.  Sections 13.0 and 14.0 were re-numbered accordingly.  References 
to Section 14.0 were corrected in Section 5.0. 
 
2.   
The notes regarding Regional Lymph Nodes have been revised on the Local 
Prostate Carcinoma Prestudy Form. 
 
Replacement pages are enclosed for the face page, pages 2, 14, 25 - 27c, 33, 33a, 40, 
40a and the Local Prostate Carcinoma Prestudy and should be inserted into your 
protocol.  Pages 27b, 27c, 33a and 40a were added to prevent extensive repagination. 
 
This memorandum serves to notify the NCI and the Southwest Oncology Group 
Statistical Center. 
 
cc: 
PROTOCOL AND INFORMATION OFFICE 
Cathy M. Tangen, Dr. P.H. 
Tracy R. Glass, M.S. 
Kathy Bingham 
Rodney Sutter 
Jean Barce 
John Taylor (CALGB) 
Gity Nasim (EMMES) 
Anita Nelson (CTSU) 
Megan Davis (AstraZeneca) 
Rose Hesselbrock (Immunex) 
Mike Proctor (OTN) 
 
 
Operations Office 
14980 Omicron Drive•San Antonio, TX 78245-3217 • Telephone 210-677-8808 • FAX 210-677-0006 • http://swog.org 


 
 
 
 
 
May 15, 2000 
 
TO: 
ALL SOUTHWEST ONCOLOGY GROUP, CCOP, AFFILIATE AND UCOP 
MEDICAL ONCOLOGISTS, RADIATION ONCOLOGISTS, SURGEONS 
AND PATHOLOGISTS; EPP INSTITUTIONS; CALGB 
 
FROM: 
Jennifer Scott Gazvoda, Protocol Coordinator 
 
RE: 
S9921, "Adjuvant Androgen Deprivation Versus Mitoxantrone Plus 
Prednisone Plus Androgen Deprivation in Selected High Risk Prostate 
Cancer Patients Following Radical Prostatectomy, Phase III."  Study 
Coordinators:  Drs. L. M. Glode, M.H.A. Hussain, G. P. Swanson, D. P. 
Wood, Jr. and W. A. Sakr. 
 
REVISION #2 
 
Study Coordinator:  L. Michael Glode, M.D.  Phone: 303/315-8801 
E-mail:  mike.glode@uchsc.edu 
 
 
 
REVISION #2 
 
The above noted study has been revised to indicate that the prestudy lymph node 
dissection should be obtained within 120 days prior to registration as a part of Good 
Medical Practice rather than eligibility.  This change is reflected in Sections 5.1 and 7.1 of 
the protocol.   
 
CALGB has been added as a participant to this study.  The addition of CALGB is 
reflected on the face page and in Sections 13.4, 14.4, 15.3, 16.0 and the model informed 
consent.  References to Section 14.4 throughout the protocol have been revised to 14.5 
accordingly.   
 
Section 13.1 has been revised to be consistent with current Southwest Oncology Group 
standard requirements. 
 
Section 3.3c and Appendix 19.4 have been revised to indicate that mitoxantrone will be 
shipped Monday through Wednesday.  The Immunex protocol number has been added 
to Appendix 19.4. 
 
Replacement pages are enclosed for the face page, pages 2, 10a, 14, 16, 24 - 27, 40 
and Appendix 19.4 and should be inserted into your protocol.  Pages 25a and 27a were 
added to prevent extensive repagination. 
 
This memorandum serves to notify the NCI and the Southwest Oncology Group 
Statistical Center. 
 
cc: 
PROTOCOL AND INFORMATION OFFICE 
Cathy M. Tangen, Dr. P.H. 
Tracy R. Glass, M.S. 
Kathy Bingham 
Rodney Sutter 
Jean Barce 
John Taylor (CALGB) 
Gity Nasim (EMMES) 
Andrew Farnsworth (AstraZeneca) 
Rose Hesselbrock (Immunex) 
 
Operations Office 
14980 Omicron Drive•San Antonio, TX 78245-3217 • Telephone 210-677-8808 • FAX 210-677-0006 • http://swog.org 


 
 
 
 
 
April 15, 2000 
 
TO: 
ALL SOUTHWEST ONCOLOGY GROUP, CCOP, AFFILIATE AND UCOP 
MEDICAL ONCOLOGISTS, RADIATION ONCOLOGISTS, SURGEONS 
AND PATHOLOGISTS; EPP INSTITUTIONS 
 
FROM: 
Jennifer Scott Gazvoda, Protocol Coordinator 
 
RE: 
S9921, "Adjuvant Androgen Deprivation Versus Mitoxantrone Plus 
Prednisone Plus Androgen Deprivation in Selected High Risk Prostate 
Cancer Patients Following Radical Prostatectomy, Phase III."  Study 
Coordinators:  Drs. L. M. Glode, M.H.A. Hussain, G. P. Swanson, D. P. 
Wood, Jr. and W. A. Sakr. 
 
REVISION #1 
 
Study Coordinator:  L. Michael Glode, M.D.  Phone: 303/315-8801 
E-mail:  mike.glode@uchsc.edu 
 
 
 
REVISION #1 
 
The above-noted study has been revised to indicate that Astra Zeneca Pharmaceuticals 
will provide Casodex® and Zoladex® free of charge to patients registered to this protocol.  
Additionally, Immunex has agreed to provide mitoxantrone free of charge to patients 
registered to Arm 2 of this protocol.  These changes are reflected in Sections 3.1c, 3.2c 
and 3.3c (supplier), the Model Informed Consent Form, and the addition of two 
appendices.  The new appendices are:  Section 19.3 - the Returned Medication Packing 
Slip (for Casodex® and Zoladex®) and 19.4 the S9921 Novantrone® Drug Request Form. 
 
Additionally, Dr. Swanson's contact information has been updated on the face page and 
in Section 8.4.  The time frame for prestudy prostatectomy has been lengthened from a 
maximum of 90 days to a maximum of 120 days prior to registration (the time frames in 
Sections 5.1 and 5.11 guidelines, as well as both Study Calendars have been revised 
accordingly).  Radiation timing guidelines have been added in Section 7.5 and two 
typographical errors were corrected in the same section.  Standard statements regarding 
IRB approval were updated in Sections 5.13 and 13.3.  The term "Affiliates" replaced the 
term "CGOPs/Member Affiliates" on the face page, Section 13.1 and Section 14.3.  The 
"Ω" footnote on both Study Calendars was corrected to clarify the intent and timing for off 
treatment follow-up.  Study Calendar 9.2 was corrected to show the intended timing of 
history and physical examinations during chemotherapy (every cycle).  Additionally, 
Section 11.5 was revised to clarify that three interim analyses are planned for this study. 
 
Replacement pages are enclosed for the face page, pages 8 - 10, 14, 15, 17, 18, 20 - 22, 
24, 25, 40 and 51.  The new appendices, Sections 19.3 and 19.4 are also enclosed and 
should be inserted at the end of your protocol.  Page 10a was added to prevent 
extensive repagination. 
 
This memorandum serves to notify the NCI and the Southwest Oncology Group 
Statistical Center. 
 
cc: 
Cathy M. Tangen, Dr. P.H. 
Gity Nasim (EMMES) 
Tracy R. Glass, M.S. 
Andrew Farnsworth (AstraZeneca) 
Kathy Sears 
Rose Hesselbrock (Immunex) 
 
Operations Office 
14980 Omicron Drive•San Antonio, TX 78245-3217 • Telephone 210-677-8808 • FAX 210-677-0006 • http://swog.org 


 
 
 
 
 
 
October 15, 1999 
 
 
TO: 
ALL SOUTHWEST ONCOLOGY GROUP, CCOP, CGOP/MEMBER 
AFFILIATES, AND UCOP MEDICAL ONCOLOGISTS, RADIATION 
ONCOLOGISTS, 
SURGEONS 
AND 
PATHOLOGISTS; 
EPP 
INSTITUTIONS 
 
 
FROM: 
Steven K. McGee, Protocol Coordinator 
 
 
RE: 
S9921, "Adjuvant Androgen Deprivation Versus Mitoxantrone Plus 
Prednisone Plus Androgen Deprivation in Selected High Risk Prostate 
Cancer Patients Following Radical Prostatectomy, Phase III."  Study 
Coordinator:  Dr. M.L. Glode. 
 
STATUS NOTICE 
 
Study Coordinator:  Michael L. Glode, M.D.  Phone: 303/315-8801 
E-mail:  mike.glode@uchsc.edu 
 
 
 
ACTIVATION 
 
The study referenced above is now open for registration.  Entire copies of the protocol 
are enclosed for your use. 
 
This memorandum serves to notify the NCI and the Southwest Oncology Group 
Statistical Center. 
 
 
 
 
 
 
 
cc: 
Cathy M. Tangen, Dr. P.H. 
Tracy R. Glass, M.S. 
Kathy Sears 
Gity Nasim (EMMES) 
 
 
 
 
 
 
 
 
 
 
 
 
Operations Office 
14980 Omicron Drive•San Antonio, TX 78245-3217 • Telephone 210-677-8808 • FAX 210-677-0006 • http://swog.org 


 
 
 
 
 
SOUTHWEST ONCOLOGY GROUP 
PROTOCOL FAST FACT SHEET 
 
THIS FORM HAS BEEN DESIGNED AS A RESOURCE ONLY AND IS NOT INTENDED FOR USE IN THE 
FULFILLMENT OF PATIENT REGISTRATION AND TREATMENT REQUIREMENTS 
 
S9921 
 
Adjuvant Androgen Deprivation versus Mitoxantrone Plus Prednisone Plus Androgen Deprivation 
in Selected High Risk Prostate Cancer Patients Following Radical Prostatectomy 
 
Treatment Initiation: 
Within 10 working day of randomization. 
Drugs Provided: 
Casodex and Zoladex will be provided by UVI, Inc. 
Mitoxantrone will be provided by OSI Pharmaceuticals. 
Prednisone must be purchased commercially. 
 
ARM 1  
 
 
 
 
 
ARM 2 
Casodex 50mg po daily X 2 years  
    OR 
 
Casodex 50mg po daily X 2 years 
Zoladex 10.8mg SC Q 3 months X 8 
 
 
Zoladex 10.8mg SC Q 3 months X 8 
 
 
 
 
 
 
 
Mitoxantrone 12mg/m2 IV day 1 Q 21 days X 6 
 
 
 
 
 
 
 
Prednisone 5mg po bid Q 21 days X 6 
 
Eligibility 
Ineligibility 
Clinically localized adenocarcinoma of the 
prostate (Stage T1– T3, N0, M0) prior to surgery 
No other therapy aimed at treatment for this diagnosis may be 
given while receiving protocol treatment 
Must have had radical prostatectomy within 120 
days of registration and fulfill one or more of the 
following: 
• 
Pathology Gleason’s  > 8 
• 
pT3b (seminal vesicle) or pT4 or N1 
• 
Pathology Gleason’s of 7 + positive margin 
• 
Pre-op PSA > 15 ng/ml or biopsy Gleason’s > 
7 or PSA > 10 ng/ml and biopsy Gleason’s > 
6 
No prior malignancy except for adequately treatment basal cell 
or squamous cell skin cancer, adequately treated Stage I or II 
cancer from which pt is currently in remission, or other cancer 
for which pt has been disease-free for 5 years. 
Testosterone level within 28 days prior to 
registration. 
Post-op PSA must be < 0.2ng/ml. 
No distant mets (must be confirmed through appropriate pre-
registration testing). 
Prior neoadjuvant hormonal therapy (< 4mos) 
prior to surgery allowed. 
No prior RT.  RT may be administered after registration. 
Pts with pre-op PSA > 20ng/ml must have pre-
study bone scan negative for metastatic disease. 
No CHF unless well controlled and LVEF > 50%. 
Pre-op EKG required within 42 days prior to 
registration.  LVEF > 50% by MUGA or 2-d echo 
(if history of cardiac disease) required within 42 
days of registration. 
 
Must be offered specimen banking. 
 
PS 0 –1. 
 
 
PRE-REGISTRATION REQUIREMENTS 
H & P, wt, PS 
Labs:  CBC/plt/diff, PSA, bili, AST, testosterone  
Scans:  EKG (required), LVEF via MUGA or 2-d echo, CT abdomen/pelvis, bone scan (if indicated)  
Tissue/serum specimen (per consent, see Section 15.0)/ 
 
PATIENT FOLLOW-UP 
Labs:  CBC/plt/diff weekly while on chemo, PSA monthly, testosterone at 4 & 7 mo, end of treatment 
Scans:  q 3 months while on chemo 
Follow-up post chemo:  q 3 mo PSA, bone scan, CT until progression 
Follow-up post progression:  q 6 months X 2 yrs, then annually for 3 yrs. 
 
*This form has been developed with the support of the SWOG Nurse Oncologists’ Committee. 


 
 
 
 
PRIVILEGED COMMUNICATION 
Revised 6/1/00 
S9921 
FOR INVESTIGATIONAL USE ONLY 
Revised 1/1/01 
Activated 10/15/99 
Revised 4/15/00 
Revised 4/1/02 
Amended 2/14/06 
Revised 5/15/00 
Revised 8/1/02 
Revised 2/1/07 
 
 
Revised 12/19/14 
 
SOUTHWEST ONCOLOGY GROUP 
 
ADJUVANT ANDROGEN DEPRIVATION VERSUS MITOXANTRONE PLUS PREDNISONE PLUS 
ANDROGEN DEPRIVATION IN SELECTED HIGH RISK PROSTATE CANCER PATIENTS FOLLOWING 
RADICAL PROSTATECTOMY 
 
PHASE III 
 
 
Page 
 
SCHEMA ......................................................................................................................... .. 3 
   1.0 
OBJECTIVES .................................................................................................................. .. 4 
   2.0 
BACKGROUND .............................................................................................................. .. 4 
   3.0 
DRUG INFORMATION ................................................................................................... .. 7 
   4.0 
STAGING CRITERIA  ..................................................................................................... .12 
   5.0 
ELIGIBILITY CRITERIA  ................................................................................................. .14 
   6.0 
STRATIFICATION FACTORS/RANDOMIZATION SCHEME ........................................ .16 
   7.0 
TREATMENT PLAN ........................................................................................................ .16 
   8.0 
TOXICITIES TO BE MONITORED AND DOSAGE MODIFICATIONS .......................... .19 
   9.0 
STUDY CALENDARS ..................................................................................................... .21 
10.0 
CRITERIA FOR EVALUATION AND ENDPOINT DEFINITIONS .................................. .23 
11.0 
STATISTICAL CONSIDERATIONS ................................................................................ .23 
12.0 
DISCIPLINE REVIEW   ................................................................................................... .24 
13.0 
REGISTRATION GUIDELINES ...................................................................................... .24 
14.0 
DATA SUBMISSION SCHEDULE .................................................................................. .27a 
15.0 
SPECIAL INSTRUCTIONS ............................................................................................. .28b 
16.0 
ETHICAL AND REGULATORY CONSIDERATIONS ..................................................... .28f 
17.0 
BIBLIOGRAPHY ............................................................................................................. .29 
18.0 
MASTER FORMS SET ................................................................................................... .32 
19.0 
APPENDIX ...................................................................................................................... .57 
  
STUDY COORDINATORS: 
AGENTS: 
 
L. Michael Glode, M.D. (Medical Oncology) 
Bicalutamide (Casodex®) (NSC-0310-0705)  
University of Colorado 
Mitoxantrone hydrochloride (Dihydroxyanthracenedione)  
Health Science Center 
                                 (DHAD) (Novantrone®) (NSC-301739) 
Division of Medical Oncology 
Prednisone (NSC-10023) 
P.O. Box 6511, Box 8117 
Goserelin acetate (Zoladex®) (D-Ser (But)6, AZgly10) (LH-RH)  
Aurora, CO  80045 
                                                   (ICI 118,630) (NSC-606864) 
Phone: 303/724-3853 
 
FAX:  303/724-3889 
 
E-mail:  mike.glode@uchsc.edu 
 
Maha H.A. Hussain, M.D. (Medical Oncology) Gregory P. Swanson, M.D. (Radiation Oncology) 
University of Michigan CCC  
UTHSC San Antonio 
Division of Hematology/Oncology  
Department of Radiation Oncology and Urology 
1500 E. Medical Center Drive  
7730 Floyd Curl Drive 
7314 CCGC 
MC 7889 
Ann Arbor, MI  48109-0946 
San Antonio, TX 78229-3900 
Phone:  734/936-8906 
Phone:  210/616-5648 
FAX:  734/615-2719 
FAX:  210/949-5085 
E-mail:  mahahuss@med.umich.edu 
E-mail:  gswanson@ctrc.net 
mb 
 
(Version Date:  12/19/14) 
 


Revised 5/15/00 
Revised 4/1/02 
S9921 
Revised 6/1/00 
Revised 8/1/02 
Page 2 
Revised 2/15/02 
Amended 2/14/06 
Revised 2/1/07 
 
 
 
 
 
STUDY COORDINATORS (contd.): 
 
David P. Wood, Jr. M.D. (Urologic Oncology) 
Cathy M. Tangen, Dr.P.H. (Biostatistics) 
University of Michigan Medical School 
Bryan Goldman, M.S. 
Department of Urology 
Southwest Oncology Group Statistical Center 
TC 2916, Box 0330 
1100 Fairview Avenue North, M3-C102 
1500 E. Medical Center Drive 
P.O. Box 19024 
Ann Arbor, MI  48109-0330 
Seattle, WA  98109-1024 
Phone:  734/763-9269 
Phone:  206/667-4623 
FAX:  734/936-9127 
FAX:  206/667-4408 
E-mail:  davwood@med.umich.edu 
E-mail:  ctangen@fhcrc.org 
 
E-mail:  bgoldman@fhcrc.org 
Wael A. Sakr, M.D. (Pathology) 
 
Harper Hospital 
Department of Pathology 
3990 John R 
Detroit, MI 48201 
Phone:  313/745-2525 
FAX:  313/745-9299 
E-mail:  wsakr@med.wayne.edu 
 
CALGB STUDY COORDINATOR: 
 
 
(CALGB Study #99904) 
 
 
Nancy Dawson, M.D. 
 
University of Maryland 
 
22 South Greene Street 
 
Baltimore, MD  21201 
 
 
 
This study is supported by the NCI Cancer Trials Support Unit (CTSU). 
 
Institutions not aligned with the Southwest Oncology Group will participate through the CTSU mechanism 
as outlined below and detailed in the CTSU logistical appendix. 
 
 
The study protocol and all related forms and documents must be downloaded from the protocol-
specific Web page of the CTSU Member Web site located at https://members.ctsu.org. 
 
 
Send completed site registration documents to the CTSU Regulatory Office.  Refer to the CTSU 
logistical appendix for specific instructions and documents to be submitted. 
 
 
Patient enrollments will be conducted by the CTSU. 
 
 
Data management will be performed by the Southwest Oncology Group.  Case report forms (with 
the exception of patient enrollment forms), clinical reports, and transmittals must be sent to the 
Southwest Oncology Group Data Operations Office unless otherwise directed by the protocol.  Do not 
send study data or case report forms to the CTSU Data Operations. 
 
 
Data query and delinquency reports will be sent directly to the enrolling site by the Southwest 
Oncology Group.  Please send query responses and delinquent data to the Southwest Oncology 
Group Data Operations Office and do not copy the CTSU Data Operations. 
 
 
Each site should have a designated CTSU Administrator and Data Administrator and must keep their 
CTEP AMS account contact information current. This will ensure timely communication between the 
clinical site and the Southwest Oncology Group Data Operations Office. 
 


 
 
S9921 
 
 
Page 2a 
 
 
Revised 2/1/07 
 
Revised 12/19/14 
 
 
 
 
ECOG STUDY COORDINATOR: 
 
Naomi Balzer-Haas, M.D. 
Department of Medical Oncology 
Fox Chase Cancer Center 
7701 Burholme Avenue 
Philadelphia, PA  19111 
 
 
CANCER TRIALS SUPPORT UNIT (CTSU) ADDRESS AND CONTACT INFORMATION: 
To submit site registration 
documents: 
For patient enrollments:  
Submit 
study 
data  
directly to the Lead 
Cooperative 
Group 
unless 
otherwise 
specified 
in 
the 
protocol:  
CTSU Regulatory Office 
1818 Market Street, Suite 1100 
Philadelphia, PA 19103 
Phone - 1-888-823-5923 
Fax – 215-569-0206 
CTSU Patient Registration 
Voice Mail – 1-888-462-3009 
Fax – 1-888-691-8039  
Hours: 8:00 AM – 8:00 PM Eastern 
Time, Monday – Friday (excluding 
holidays) 
 
[For CTSU patient enrollments that must 
be completed within approximately one 
hour, 
or 
other 
extenuating 
circumstances, 
call 
301-704-2376.  
Please use the 1-888-462-3009 number 
for ALL other CTSU patient enrollments.] 
Southwest 
Oncology 
Group Data Operations 
Office 
 
Fax: 800/892-4007 
 
Do not submit study data 
or forms to CTSU Data 
Operations. Do not copy 
the 
CTSU 
on 
data 
submissions. 
For patient eligibility or treatment-related questions contact the Study PI of the Coordinating Group.  
For questions unrelated to patient eligibility, treatment, or data submission contact the CTSU Help 
Desk by phone or e-mail:  
CTSU General Information Line – 1-888-823-5923, or ctsucontact@westat.com. All calls and 
correspondence will be triaged to the appropriate CTSU representative.  
The CTSU Public Web site is located at: www.ctsu.org  
The CTSU Registered Member Web site is located at https://members.ctsu.org 
 
 
 
 
 
 
 
 
 
 
 
 
Please refer to all questions regarding chemotherapy treatment or dose modifications to Dr. L. 
Michael Glode.  For radiation therapy related questions, contact Dr. Gregory P. Swanson. 
 
 
PARTICIPANTS 
 
ALLIANCE/Alliance for Clinical Trials in Oncology 
 
ECOG-ACRIN/ECOG-ACRIN Cancer Research Group 
SWOG/SWOG 


 
S9921 
 
Page 3 
 
Amended 2/14/06 
 
 
 
 
 
SCHEMA 
 
 
 
Prostate Cancer 
Clinical Stage T1-T3 
 
 
 
 
 
Radical Prostatectomy 
(high risk as defined in Sections 5.1a - d) 
 
 
 
 
 
Any pT, N0, N1 
 
 
 
 
 
 
 
 
 
 
 
 
Casodex 
Mitoxantrone and  
and Zoladex 
Prednisone X 6 cycles  
X 24 months  
plus Casodex and 
 
Zoladex X 24 months  
 
 
 
 
 
 
 
 
 
 
 
RANDOMIZE 
Follow for Survival or 
for a maximum of 15 


Amended 7/1/00 
Amended 2/14/06 
S9921 
 
Page 4 
 
 
 
1.0 
OBJECTIVES 
 
1.1 
The primary objective is to evaluate overall survival using adjuvant systemic therapy in 
high risk localized prostate cancer patients following radical prostatectomy.  Disease-free 
survival will also be evaluated.  Patients will be randomized to one of the following arms: 
 
a. 
bicalutamide (Casodex®) + goserelin acetate (Zoladex®) 
 
b. 
mitoxantrone + prednisone administered with Casodex® + Zoladex®. 
 
1.2 
To compare qualitative and quantitative toxicity between the two study arms. 
 
1.3 
To compare the two treatment arms with respect to PSA progression-free survival. 
 
1.4 
To test whether PSA progression is a surrogate endpoint for survival or disease-free 
survival in this clinical trial. 
 
1.5 
To evaluate promising biomarkers with respect to predicting PSA progression, disease-
free survival, and overall survival. 
 
1.6 
To collect specimens (blood and prostatectomy blocks) for future biomarker 
(immunohistochemistry, proteomics, genomics) studies and correlations with outcomes. 
 
2.0 
BACKGROUND 
 
Introduction 
 
Historically the management of localized adenocarcinoma of the prostate has followed a monotherapy 
strategy.  (1, 2)  For several decades, patients thought to have organ-confined prostate cancer or 
minimal risk of extracapsular disease were offered either radical prostatectomy or radical irradiation. 
Although these therapies are considered curative, it is well recognized that the potential for cure is 
highly dependent on stage and grade.  Approximately 30% of patients with organ-confined prostate 
cancer and up to 60% of patients with T3 tumors are at risk for a systemic relapse despite curative 
intent radical prostatectomy.  (3)  The figure is higher if the nodes are positive. 
 
In patients with clinically organ confined prostate cancer, freedom from biochemical relapse at 5 years 
is related to Gleason score, PSA, pathologic T and N stage and status of the surgical margin.  (4 - 8)  
Freedom from relapse at 5 years ranging from 83% - 95% is especially associated with Gleason score 
of ≤ 6, pT1-T2 with a pre-therapy PSA of < 10 ng/ml.  (5)  A preoperative PSA of > 20 ng/ml, poorly 
differentiated histology (Gleason ≥ 8), seminal vesicle or extensive surgical margin involvement or 
nodal metastases define a high risk group of patients with a 50% or greater biochemical relapse rate at 
5 years.  (5 - 8)  These data suggest the presence of occult systemic disease at time of initial 
diagnosis underscoring the potential importance of early systemic therapy.  The case for the latter may 
be strengthened by the knowledge that recurrent/metastatic prostate cancer is currently incurable in 
the majority of cases. 
 
A greater recognition of the importance of eliminating subclinical residual disease or occult systemic 
metastases in a variety of solid tumors has led to the investigation and development of multimodality 
treatment approaches. Survival improvements had become more achievable particularly with the 
addition of systemic therapy such as the case in breast, colorectal, and lung cancers and melanoma.  
(9 - 12)  By comparison the evolution of multimodality therapy for prostate cancer has been relatively 
slow.  This lag may in part be attributed to the perceived lack of precise prognostic criteria capable of 
predicting relapse risk for a particular individual, the long natural history which impacts on the timely 
evaluation of therapeutic efficacy, the lack of "effective" systemic nonhormonal therapy and the 
concern regarding the morbidity and negative quality of life effects of long-term hormonal therapy.  
However, a number of recent innovations have made it more feasible to investigate multimodality 
strategies including the introduction of PSA, the improvement in patient selection for local therapy and 
in surgical and radiation techniques, the development of Iong-acting reversible androgen- suppressing 
agents with minimal side effects and the development of systemic chemotherapy with modest but 
definite activity in the setting of refractory prostate cancer. 
 
Neoadjuvant Therapy 
 
In prostate cancer the use of systemic therapy (adjuvant or neoadjuvant), is not a new concept.  Since 
the early 1970s, androgen deprivation has been investigated primarily in patients with locally advanced 
prostate cancer undergoing radiation therapy.  Several trials have been reported including a 
randomized 
RTOG 
trial 
comparing 
4 
months 
of 
neoadjuvant 
hormonal 
therapy 
plus 


 
S9921 
 
Page 5 
 
 
 
local irradiation to an irradiation-only arm in patients with locally advanced disease (RTOG 
86-10). (13,14)  A statistically significant improvement in local control and in 5 years incidence of 
distant metastases in favor of the combined therapy arm was demonstrated.  (13) 
 
A similar approach was adopted for patients undergoing radical prostatectomy, as 30%-60% of 
patients clinically thought to have organ-confined prostate cancer will have extraprostatic 
disease, thus are at a higher risk for relapse.  (15, 16)  Neoadjuvant androgen deprivation was 
used to decrease the number of patients with positive surgical margins with the assumption that 
this would translate to fewer relapses. The data from these studies to date are mixed in that 
neoadjuvant hormonal therapy can decrease the incidence of positive surgical margins but does 
not improve the disease-free or overall survival.  (17 - 22)  Initial reports with short follow up have 
suggested no difference in biochemical recurrence rates between patients treated with 
neoadjuvant androgen deprivation plus radical prostatectomy and those treated with radical 
prostatectomy alone.  (22)  While the reasons for the lack of objective benefits are unclear it may 
be that brief exposure to androgen deprivation is ineffective in controlling occult systemic 
disease. The latter is not entirely surprising since in breast cancer, another hormone sensitive 
tumor, it has been demonstrated that longer duration of therapy is superior to shorter duration of 
hormonal manipulation.  (23)  Furthermore, the neoadjuvant studies that have been conducted 
were designed with short follow-up to detect pathologic but not survival differences, and it could 
be suggested that hormonal therapy can induce changes in the prostate cancer cells making it 
difficult for the pathologist to recognize their existence.  (24)  The latter would lead to a false 
increased rate of organ-confined tumors.  With this data it is reasonable to conclude that the role 
of neoadjuvant hormonal therapy prior to radical prostatectomy remains to be determined. 
 
Adjuvant Therapy 
 
Considering that:  a) appropriate patient selection is crucial for the success of combined therapy 
trials; b) current determinants of recurrence are based predominantly on pathologic findings and 
c) the fact that longer systemic therapy duration is likely to be necessary, it would seem quite 
logical to investigate adjuvant systemic therapy in patients with high risk localized prostate 
cancer.  Current data which will be summarized in the ensuing paragraphs suggest that systemic 
therapy in the form of short course or permanent androgen deprivation results predominantly in 
prolongation of disease free survival, however, statistically significant survival improvements 
were demonstrated in only one study.  A significant disease free survival advantage was noted at 
5, 10, and 15 years in favor of diethylstilbestrol (DES) plus radiation therapy as compared with 
standard dose irradiation in 78 patients with locally advanced prostate cancer.  (25)  The lack of 
an overall survival advantage was attributed to the greater incidence of intercurrent disease-
related mortality in the DES arm.  The second study was conducted by the National Prostate 
Cancer Project (NPCP) in radical prostatectomy (NPCP-900, 184 patients) or radiation therapy 
(NPCP-1000, 253 patients) treated patients.  (26)  Following lymph node dissection, patients 
were randomized to observation, cyclophosphamide or estramustine.  Recent update of the result 
with a 14.3 years follow-up indicate that the estramustine treated patients in both studies 
demonstrated improved progression free survival (PFS) especially in patients with T3 or T4 or 
Grade 3 tumors and in radiation treated patients with extensive nodal metastases. 
 
The introduction of long acting reversible gonadal suppressing agents has fostered the 
development of a new generation of adjuvant therapy trials.  Two randomized trials have been 
conducted comparing combined therapy to radiation alone, one by the Radiation Therapy 
Oncology Group (RTOG) and the other by the European Organization for Research and 
Treatment of Cancer (EORTC), in patients with locally advanced or node positive prostate cancer.  
The RTOG trial used life long or until progression androgen suppression with goserelin and the 
EORTC trial tested three years of adjuvant goserelin.  (27, 28)  With 945 evaluable patients in the 
former and 401 evaluable patients in the latter, combined modality therapy was superior with 
regard to disease-free survival in both trials.  Overall survival superiority was observed only in the 
EORTC trial.  However, for patients with centrally reviewed tumors with a Gleason score of 8 - 10, 
in the RTOG trial, the difference in actuarial five year survival was in favor of the adjuvant therapy 
arm (66% vs. 55%, P=0.03).  The discrepancy in outcome with regard to survival between the two 
trials is unclear.  It is interesting to note that the five year survival in the experimental arms of the 
two studies is comparable (75% and 79%, respectively), however the control arm in the RTOG 
study had a better survival than the EORTC study (71 % vs. 62%, respectively).  This difference 
in 


 
S9921 
 
Page 6 
 
 
 
survival may be related, in part, to different patterns of clinical practice as they relate to timing of 
salvage hormonal therapy in the USA and Europe and differences in patients' characteristics. 
 
With this background we organized a multidisciplinary consensus conference in April of 1997 to 
answer three specific questions: 1) Considering 1997 diagnosis and treatment standards, is 
prostate cancer a curable disease in the vast majority of patients undergoing radical 
prostatectomy for clinically localized prostate cancer?, 2) If not, can we identify the subset of 
patients that is likely to be at a high risk of relapse using current refined clinical/pathologic 
criteria?, 3) If a high risk subset can be defined, should adjuvant systemic therapy be investigated 
and what should the design be? 
 
The conference recommendations were further endorsed by members of the Genitourinary 
Cancer Committee of the Southwest Oncology Group and the Prostate Committee of the Cancer 
and Leukemia Group-B (CALGB).  These recommendations provide the basis for this proposal.  
The eligibility criteria used in this proposal are thought to identify a subset of patients with a 40% 
or greater risk of relapse.  The primary endpoint is survival.  Much discussion centered around 
the treatment arms.  A "no therapy" arm versus hormonal therapy were both discussed as 
potential controls.  However, the inherent difficulties in randomizing a high risk group to "no 
therapy" coupled with emerging data (discussed above) on early systemic therapy suggesting an 
advantage in at least the disease free survival, the fact that survival outcome from an adjuvant 
trial will not be ready for at least 10 years, with the desire to jump start the process and the 
awaited results of two major trials (the intergroup D1 adjuvant hormone trial and the adjuvant 
bicalutamide trial) led to choosing primary androgen deprivation as the control arm. 
 
Therapy intensification using chemohormonal therapy was also deemed an important step based 
on proven successes of modestly active chemotherapy in other solid tumors such as colon, lung 
and melanoma when advanced to earlier stages, and attempting to change the paradigm in the 
management of this disease.  Both estramustine and mitoxantrone based combination 
chemotherapy were considered. However, despite the apparent improved response rates with 
estramustine based combination chemotherapy, it was recognized that no large scale or Phase 
III data are currently available for these combinations in contrast to the mitoxantrone + 
prednisone combination therapy.  (29 - 32) Although the latter combination had no impact on 
survival, the outcome from the two randomized trials indicate a higher proportion and duration of 
palliative, objective and PSA response rates in favor of the mitoxantrone/corticosteroid arm as 
compared with corticosteroid control, in addition to a favorable side effect profile.  (31, 32) 
 
With this background we propose a Phase III randomized trial targeting high risk surgically 
treated prostate cancer patients.  A combined hormonal therapy arm will be compared with 
chemohormonal therapy arm. 
 
The role of post prostatectomy radiation in patients with locally advanced disease is uncertain.  
Patients with margin, capsular, seminal vesicle, and lymph node involvement have a significant 
risk of local failure.  Retrospective studies indicate that postoperative radiation could reduce the 
risk of local failure significantly.  (33 - 35)  It is unclear as to what degree this impacts on disease 
free and overall survival.  (33 - 36)  In 1987, the Southwest Oncology Group initiated a 
postprostatectomy study (SWOG-8794) that randomized patients with T3, N0, M0 disease to 
adjuvant radiation or none.  The goal was to determine the effect of postoperative radiation on 
the disease free survival rate.  The results of that study are to be reported in 2002.  Accrual to the 
study was slower than expected, partially due to the increasing trust and dependence on PSA as 
a marker of failure.  Since not all patients with T3 disease fail, it is appealing to wait for the 
disease to declare itself before initiating potentially morbid treatment.  (37)  On the other hand, 
there is some indication that earlier radiation might have a better chance of improving the 
outcome.  (38, 39)  Given that the question is uncertain, the Southwest Oncology Group will allow 
investigators to continue to utilize post-operative radiation to the prostate fossa at their discretion 
on this study. 
 


 
S9921 
 
Page 7 
 
 
 
Minority Participation 
 
There is particular concern about prostate cancer in African American (AA) men where the 
incidence is higher and the prognosis appears to be worse.  The issue in this trial is whether AA 
patients will have a different outcome as compared to non AA patients, and more specifically 
whether clinically meaningful arm-specific differences between AA and non AA patients can be 
detected.  At this time there are no data suggesting that such a relationship exists.  This study will 
provide an opportunity to perform exploratory analyses of the relationship of survival to AA status 
and adjuvant therapy.  The Southwest Oncology Group experience in accruing AA patients to an 
early stage prostate cancer trial has been in SWOG-8794 where 20% of the pathologic Stage C 
patients accrued are AA (which is considerably higher than that which would be expected based 
on the proportion of older AA men in the population). 
 
Anticipated accrual to this study by race follows: 
 
 
American  
Asian or  
Black, not 
Hispanic 
White, not 
Other or 
Total 
Indian or 
Pacific 
of Hispanic 
 
of Hispanic Unknown 
Alaskan 
Islander 
Origin 
 
Origin 
Native 
 
 
1 
5 
313 
41 
1,000 
0 
1,360 
 
 
As this is a prostate cancer study, no females will be registered. 
  
3.0 
DRUG INFORMATION 
 
3.1 
Bicalutamide (Casodex®) (NSC-0310-0705) 
 
a. 
DESCRIPTION 
 
Chemistry:  Casodex® is a racemic mixture containing two enantiomers, (2RS)-
4'-Cyano-3(4-fluorophenylsulphonyl)-2-hydroxy-2-methyl-3'-trifluoromethyl) 
propionanilide. 
 
Casodex® is an active non-steroidal antiandrogen and its antiandrogen activity 
resides exclusively in the (-) or (R) enantiomer.  Unlike flutamide, it is peripherally 
selective and does not cause a rise in serum LH or Testosterone in male rats 
and dogs.  This peripheral selectivity may be because it penetrates poorly the 
CNS and Hypothalamus (the site of negative feedback of androgens).  In 
humans, rises in LH, Testosterone and Estradiol concentrations were seen.  
These rises were not dose related.  In 90%, testosterone levels remained within 
normal limits.  There was no significant rise in mean serum FSH. 
 
b. 
TOXICOLOGY 
 
In rats, besides antiandrogenic changes, there was evidence of hepatocyte 
hypertrophy and basophilia.  In dogs treated for 6 months, there was increased 
heart rate with decreased PR interval, transient decrease in circulating PMNs 
and increased plasma cholesterol.  No cardiac pathology was found.  In a mouse 
oncogenicity study, an increased incidence of hepatocellular carcinoma was 
observed in the top dose male group (75 mg/kg/day).  The no effect dose level 
for hepatocellular carcinoma in this study was 15 mg/kg/day with steady state 
blood levels in excess of 10 µg/ml.  The mechanism for this tumor formation is a 
non-genotoxic, phenobarbitone-type MFO induction and is not considered to 
represent a risk for humans.  A two-year study in rats and female mice at similar 
doses did  not show an increased incidence of hepatic tumors. 


Revised 4/15/00 
S9921 
Amended 2/14/06 
Page 8 
 
 
 
 
 
Casodex® has been given to over 3,500 men in 35 different clinical studies 
worldwide, in doses up to 600 mg daily.  When Casodex® is given in combination 
with an LHRH analog, the pharmacologic adverse event profile is dominated by 
the LHRH analog and includes hot flashes (53%), gynecomastia (9%) and breast 
pain (6%).  Other adverse events reported regardless of causality included 
diarrhea (12%), constipation (22%), nausea (15%) and abdominal pain (11%).  
Other adverse were reported, such as fatigue (22%), pain (35%), back pain 
(25%), pelvic pain (21%), infection (18%), peripheral edema (13%), dyspnea 
(13%), nocturia (12%), hematuria (12%), anemia (11%), dizziness (10%).  
Casodex® has been associated with changes in liver function, although these are 
infrequent (7%) and rarely occur with jaundice.  Many of these changes improved 
or resolved despite continuation of bicalutamide therapy.  There have been no 
reports of fatal hepatotoxicity associated with Casodex® therapy. 
 
c. 
PHARMACOLOGY 
 
Pharmacokinetics: 
 
Animal studies:  After oral single dose administration, absorption of the 
compound was slow with peak concentration occurring 3 - 12 hours and plateau 
between 2 and 48 hours.  There was non-proportional increase in plasma levels 
with increasing doses.  Elimination half life ranges from 17 - 28 hours in male 
rats, 21 - 29 hours in female rats and 5 - 7.5 days in dogs.  91 - 96% of 
Casodex® is bound to plasma protein. 
 
Human studies:  After single doses, mean time for peak plasma concentration 
was 6 hours at 10 and 30 mg, but at 50 mg, it was 16 hours.  Mean plasma 
elimination half lives after 12 weeks of 10, 30, 50, 100 mg/day was 7 - 10 days.  
This finding was consistent with single dose data.  In patients given daily doses 
of 50 mg, mean plasma concentration was 10 ug/ml at 12 weeks.  After single 
doses, there was linear increase with doses between 10 and 50 mg, but became 
non-linear at doses of 50 - 100 mg.  At 100 mg, the oral bioavailability is reduced 
by 30% but plasma elimination half life is unchanged.  Casodex® is extensively 
metabolized and metabolites are excreted by both the biliary and urinary system. 
 
Formulation:  Casodex® is prepared as round, film-coated green or white tablets 
containing standard recipients and 50 mg of the drug. 
 
Storage and stability:  All packages of Casodex® should be stored securely in a 
dry place at room temperature. 
 
Route of Administration:  Casodex® is to be administered orally in tablet form as 
a once-daily oral dose.  Patients should be instructed to take one tablet once 
daily. 
 
Supplier:  Casodex™ is commercially available, however for this study Astra 
Zeneca Pharmaceuticals, Inc. will supply the drug to UVI, Inc. for distribution.  
Casodex™ will be supplied as white tablets containing 50 mg each of micronized 
drug (F6625).  Casodex™ will be provided in bottles of 100 tablets.  Institutions 
are instructed to delay ordering the drug from the UVI, Inc. until they have a 
patient in mind for registration.  Drug may be requested by contacting the clinical 
customer service staff at UVI, Inc. at Phone:  800/370-2508, Fax:  650/745-3877, 
Monday - Friday 8:00 a.m. - 5:00 p.m., PST.  Please note that drug is shipped via 
UPS Ground and may take up to 5 business days for delivery.  Drug must be 
ordered prior to 3:00 p.m. Eastern Time in order to be shipped that day.  All 
unused drug supplies will be returned to UVI, Inc. for destruction using the 
Returned Medication Packing Slip (see Section 19.3), detailing the material being 
returned. 
 


Revised 4/15/00 
S9921 
Amended 2/14/06 
Page 9 
 
 
 
 
3.2 
Goserelin Acetate (Zoladex®) D-Ser (But)6, Azgly10) (LH-RH) (ICI 118,630) (NSC-
606864) 
 
a. 
DESCRIPTION 
 
Chemistry:  The physical form of Zoladex is an off-white powder. 
 
Chemical Structure: 
 
pyro-Glu-His-Trp-Ser-Tyr-D-Ser (But)-Leu-Arg-Pro-Azgly-NH2 
 
Molecular Weight:  1269 (as base) 
 
Solubility:  Soluble in water, dimethylformamide and dimethylsulfoxide. 
 
b. 
TOXICOLOGY 
 
Animal Studies:  In laboratory animals, the acute toxicity of ICI 118,630 was 
found to be very low in comparison to its pharmacologic potency.  Intravenous 
doses of up to 6 mg/kg were without any adverse effects in rats undergoing LD50 
studies.  No significant pharmacological activity was apparent in the 
cardiovascular, respiratory, central nervous, renal and metabolic, coagulation or 
gastric acid secretory systems.  In rats, but not the cat, mouse, dog or rabbit, 
long-term dosing of Zoladex has resulted in benign pituitary adenomas. 
 
Human Toxicity:  Most side effects attributed to LH-RH agonists have been due 
to testosterone withdrawal (e.g., hot flashes, sweats, impotence, breast 
enlargement, nausea and dizziness).  Skin reaction and irritation at the injection 
site (rarely, < 2%) have also been observed.  Tumor flares have been reported in 
a  small number of patients receiving LH-RH agonists.  Flare reactions usually 
consist of minor complications such as increased bone pain and therapy may be 
continued; however, potentially dangerous complications (e.g. incipient spinal 
cord compression or ureteral obstruction) must be averted by discontinuing 
Zoladex treatment and beginning corrective therapy immediately. 
 
c. 
PHARMACOLOGY 
 
Kinetics:  Subcutaneous depot given on Days 1 and 29 to patients with prostatic 
cancer with normal renal and hepatic function revealed a peak concentration 12 
to 15 days after administration, with peak values of 2.64 ng/ml and 2.44 ng/ml.  
There was no drug accumulation.  In an aqueous formulation given daily to 8 
patients with advanced prostatic cancer, peak serum concentration was 12.8 
ng/ml and the half life was 6.1 hours.  The mean area under the curve in the 
dosing interval was 65 ng h/ml and mean total body clearance was 120.1 ml/min. 
 
Formulation:  Zoladex is supplied as a 10.8 mg solid depot formulation preloaded 
in a disposable syringe device mounted on a #14 gauge hypodermic needle. 
 
Storage and Stability:  The sterile unit will be enclosed in a sealed light and 
moisture proof package.  The package should be stored securely in a dry place 
at room temperature (not to exceed 25°C or 77°F).  Before being opened, each 
package must be inspected for damage in which case the depot should not be 
used.  Being sterile, the syringe should be removed from its package only 
immediately before required. 
 
Administration:  Zoladex will be injected every 3 months (13 weeks).  No 
anesthetic is required; however, local anesthetics may be applied prior to 
injection if desired.  After cleaning with an alcohol swab, a small area of skin on 
the anterior abdominal wall will be anesthetized by injecting 0.2 ml of 1.0% 
lidocaine hydrochloride intradermally or by applying topical ethyl chloride.  
Zoladex 
will 
then 


Revised 4/15/00 
S9921 
Amended 2/14/06 
Page 10 
 
 
 
 
be injected into the subcutaneous fat using aseptic technique.  After injecting 
Zoladex depot, for the first time only, the overlying skin will be indelibly marked 
with a single spot.  In the unlikely event of the depot needing to be surgically 
removed (e.g., severe anaphylaxis), this mark will facilitate such a procedure.  
After checking to ensure that the depot has been discharged, the used syringe 
will be broken and discarded in a safe manner. 
 
Supplier: Zoladex™ is commercially available, however, for this study Astra 
Zeneca Pharmaceuticals, Inc. will supply the drug to UVI, Inc. for distribution.  
Zoladex™ for the study will be supplied in packages of one preloaded syringe, 
either the 3.6 mg solid depot or the 10.8 mg solid depot formulation.  
Participating institutions are instructed to delay ordering the drug from UVI, Inc. 
until they have a patient in mind for registration.  Drug may be requested by 
contacting the clinical customer service staff at UVI, Inc. at Phone:  800/370-
2508, Fax:  650/745-3877, Monday - Friday 8:00 a.m. - 5:00 p.m., PST.  Please 
note that drug is shipped via UPS Ground and may take up to 5 business days 
for delivery.  Drug must be ordered prior to 3:00 p.m. Eastern Time in order to be 
shipped that day.  All unused drug supplies will be returned to UVI, Inc. for 
destruction using the Returned Medication Packing Slip (see Section 19.3), 
detailing the material being returned. 
 
3.3 
Mitoxantrone hydrochloride (Dihydroxyanthracenedione) (DHAD) (Novantrone®) (NSC-
301739) 
 
a. 
DESCRIPTION 
 
Mitoxantrone is a synthetic antineoplastic anthracenedione.  All of the 
aminoanthraquinones are potent inhibitors of DNA and RNA synthesis in vitro 
and bind strongly to DNA as evidenced by Tm values.  It would appear, because 
not all of them have antitumor effects, that the antitumor activity is due to some 
mechanism other than, or in addition to, DNA binding and the inhibition of nucleic 
acid synthesis.  Since a number of bis(substituted amino-alkyl amino) 
anthraquinones have been shown to be intercalating agents, mitoxantrone most 
likely acts through intercalation between base pairs of the DNA double helix. 
 
b. 
TOXICOLOGY 
 
Human Toxicology:  The dose-limiting toxicities are myelosuppression and 
cardiotoxicity.  Leukopenia and thrombocytopenia were maximal by day nine and 
both had resolved by Day 19 - 21.  Other toxicities seen occasionally include 
stomatitis, nausea and vomiting, phlebitis, mild elevations in SGOT, alopecia, 
dyspnea, urticaria, rash, hypotension, arrhythmias, chest pains and green urine 
and serum.  Cardiotoxicity may be more common in patients previously treated 
with anthracycline, mediastinal radiotherapy or preexisting cardiac disease.  
Mitoxantrone may cause fetal anomaly and is mutagenic in bacterial systems.  
Extravasation may cause local tissue necrosis. 
 
c. 
PHARMACOLOGY 
 
Kinetics:  Pharmacologic studies done in dogs showed that the drug disappears 
rapidly from plasma (drug found only in the three-minute sample) and that ≤ 1% 
appears in the urine in a 24-hour period.  Initial clinical pharmacology studies in 
man show a rapid distribution half-life (eight minutes) and an elimination half-life 
of two hours.  Most of the drug is probably excreted in the biliary system, as only 
about 10% of the drug is excreted in the urine.  Additional experience at the 
University of Texas Health Science Center in San Antonio shows an every-three-
week schedule to be tolerable. 
 


 
S9921 
 
Page 10a 
 
Revised 4/15/00 
 
Revised 5/15/00 
 
Amended 7/1/00 
 
Revised 2/1/01 
 
Revised 7/15/01 
 
Revised 11/1/02 
 
Revised 5/15/03 
 
Amended 2/14/06 
 
 
 
 
Formulation:  Mitoxantrone is supplied as a dark blue sterile concentrated 
solution containing mitoxantrone hydrochloride equivalent to 2 mg/ml 
mitoxantrone free base.  The concentrate is supplied in 12.5 ml vials and must 
be diluted prior to injection.  Inactive ingredients include sodium acetate 
(0.0005% w/v) and acetic acid 0.046%, sodium chloride (0.800% w/v), and water 
for injection. 
 
Storage and Stability:  The product contains no preservatives and is stored at 
room temperature.  Discard any unused drug after eight hours of entering the 
ampule.  The expiration date for each ampule of mitoxantrone is provided on the 
label.  When 2.5 mg of parenteral solution is admixed at room temperature with 
500 cc of 5% Dextrose for injection, USP or sodium chloride injection, USP, the 
solutions maintain their potency for 48 hours. 
 
Administration:  Mitoxantrone should be given in a solution of 100 cc of D5W as 
an infusion into a well-running IV over 30 minutes.  DO NOT GIVE IV PUSH. 
 
Supplier:  Mitoxantrone is commercially available however, for this study OSI 
Pharmaceuticals will supply and distribute the drug free of charge.  Institutions 
are instructed to delay ordering the drug until after randomization.  Drug may be 
requested by faxing an S9921 Novantrone® Drug Request Form (see Section 
19.4) to Priority Healthcare Corporation at 866/203-4684.  Mitoxantrone will be 
shipped Monday through Wednesday.  A minimum of two days notice is required. 
 
The mitoxantrone shall be shipped to the Investigators in appropriately marked 
containers and shall be used solely for conducting S9921.  Accurate records of 
all mitoxantrone received and dispensed shall be maintained by the 
Investigators, and all mitoxantrone shall be stored by the Investigators in a 
secure and locked location to prevent the theft or misuse.  All used vials of 
mitoxantrone shall be discarded in accordance with applicable federal and state 
laws, rules and regulations.  Upon the completion or termination of S9921 or 
termination of the Agreement, whichever occurs first, all expired or unused Study 
Drug shall, at the direction of Company, either be returned to Company or 
discarded in accordance with all applicable federal and state laws, rules, and 
regulations. 
 


 
S9921 
 
Page 11 
 
 
 
3.4 
Prednisone (NSC-10023) 
 
a. 
DESCRIPTION 
 
Prednisone is a glucocorticoid rapidly absorbed from the GI tract. 
 
b. 
TOXICOLOGY 
 
Human Toxicology:  Possible adverse effects associated with the use of 
prednisone are:  fluid and electrolyte disturbances, congestive heart failure in 
susceptible persons, hypertension, euphoria, personality changes, insomnia, 
mood swings, depression, exacerbation of infection (e.g., tuberculosis), 
exacerbation or symptoms of diabetes, psychosis, muscle weakness, 
osteoporosis, vertebral compression fractures, pancreatitis, esophagitis, peptic 
ulcer, dermatologic disturbances, convulsions, vertigo and headache, endocrine 
abnormalities, ophthalmic changes, and metabolic changes.  Some patients have 
experienced itching and other allergic, anaphylactic or other hypersensitivity 
reactions.  Withdrawal from prolonged therapy may result in symptoms including 
fever, myalgia and arthralgia.  Phenytoin phenobarbitol and ephedrine enhance 
metabolic clearance of corticosteroids. 
 
Corticosteroids should be used cautiously in patients with hypothyroidism, 
cirrhosis, ocular herpes simplex, existing emotional instability or psychotic 
tendencies, 
nonspecific 
ulcerative 
colitis, 
diverticulitis, 
fresh 
intestinal 
anastomoses, peptic ulcer, renal insufficiency, hypertension, osteoporosis and 
myasthenia gravis.  Immunization procedures (especially smallpox vaccination) 
should not be undertaken in patients on corticosteroids. 
 
c. 
PHARMACOLOGY 
 
Kinetics:  Natural and synthetic glucocorticoids are readily and completely 
absorbed from the GI tract.  Prednisone is very slightly soluble in water.  
Glucocorticoids have salt-retaining properties.  The anti-inflammatory property of 
this drug is its ability to modify the body's immune system.  On the other hand, 
glucocorticoids suppress the body's response to viral as well as bacterial 
infections.  Equivalent doses are as follows: 
 
Dexamethasone Methyl-prednisolone Prednisolone 
Hydrocortisone Cortisone 
 
and Triamcinolone 
and Prednisone 
 
 
0.75 mg 
4 mg 
5 mg 
20 mg 
25 mg 
 
Formulation:  Prednisone is available in 2.5 mg, 5 mg, 10 mg, 20 mg and 50 mg 
tablets. 
 
Storage and Stability:  Prednisone should be stored at room temperature. 
 
Administration:  Prednisone is administered orally. 
 
Supplier:  Prednisone is commercially available and should be purchased by 
third party.  Prednisone will not be supplied by the NCI. 
 
 


 
S9921 
 
Page 12 
 
 
 
4.0 
STAGING CRITERIA 
 
(TAKEN FROM THE MANUAL FOR STAGING OF CANCER, AJCC, FIFTH EDITION.) 
 
DEFINITION OF TNM 
 
Clinical Staging.  Primary tumor assessment includes digital rectal examination of the prostate 
and histologic or cytologic confirmation of prostatic carcinoma.   
 
Pathologic Staging.  Histologic examination of the resected specimen is required.  Total 
prostatoseminalvesiculectomy and pelvic lymph node dissection are required for pathologic 
staging.  
 
Definition of TNM 
 
Primary Tumor, Clinical (T) 
 
TX 
Primary tumor cannot be assessed. 
T0 
No evidence of primary tumor. 
 
T1 
Clinically inapparent tumor not palpable or visible by imaging 
 
T1a 
Tumor incidental histologic finding in 5% or less of tissue resected 
 
T1b 
Tumor incidental histologic finding in more than 5% of tissue resected 
 
T1c 
Tumor identified by needle biopsy (e.g., because of elevated PSA) 
 
 
T2 
Tumor confined within the prostate* 
 
T2a 
Tumor involves one lobe 
 
T2b 
Tumor involves both lobes 
 
 
T3 
Tumor extends through the prostatic capsule** 
 
T3a 
Extracapsular extension (unilateral or bilateral) 
 
T3b 
Tumor invades the seminal vesicle(s) 
 
 
T4 
Tumor is fixed or invades adjacent structures other than the seminal vesicles:  bladder 
neck, external sphincter, or rectum, levator muscles and/or pelvic wall 
 
*Note:  Tumor found in one or both lobes by needle biopsy, but not palpable or reliably visible by 
imaging, is classified as T1c. 
**Note:  Invasion into the prostatic apex or into (but not beyond) the prostatic capsule is not 
classified as T3, but as T2. 
 
Primary Tumor, Pathologic (pT) 
 
pT2*** Organ confined 
 
pT2a 
Unilateral 
 
pT2b 
Bilateral 
 


 
S9921 
 
Page 13 
 
 
 
 
pT3 
Extraprostatic extension 
 
pT3a 
Extraprostatic extension 
 
pT3b 
Seminal vesicle invasion 
 
 
pT4 
Invasion of bladder, rectum 
 
***Note:  There is no pathologic T1 classification. 
 
Regional Lymph Nodes (N) 
 
NX 
Regional lymph nodes cannot be assessed 
 
N0 
No regional lymph node metastasis 
 
N1 
Metastasis in a single lymph node or nodes. 
 
Distant Metastasis*** (M) 
 
MX 
Distant metastasis cannot be assessed 
 
M0 
No distant metastasis 
 
M1 
Distant metastasis 
 
M1a 
Nonregional lymph node(s) 
 
M1b 
Bone(s) 
 
M1c 
Other site(s) 
 
***NOTE:  When more than one site of metastasis is present, the most advanced category is 
used.  pM1c is most advanced. 
 


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Revised 1/1/01 
Page 14 
Revised 6/1/00 
Revised 7/1/01 
Revised 4/1/02 
 
 
Amended 2/14/06 
 
 
 
 
 
 
5.0 
ELIGIBILITY CRITERIA 
 
Each of the criteria in the following section must be met in order for a patient to be considered eligible for 
registration.  Use the spaces provided to confirm a patient's eligibility.  For each criterion requiring test 
results and dates, please record this information on the Prestudy Form and submit to the Data Operations 
Center in Seattle (see Section 14.0).  Any potential eligibility issues should be addressed to the Data 
Operations Center in Seattle at 206/652-2267 prior to registration. 
 
SWOG Patient No.   
 
 
Patient's Initials (L, F, M)   
 
 
5.1 
All patients must have a histologic diagnosis of adenocarcinoma of the prostate and must 
be considered to have clinically localized disease (Stage T1-T3, N0, M0), and be 
considered operable for cure by their primary urologic surgeon.   
 
Patients must have had a radical prostatectomy within 120 days prior to registration and 
must fulfill one or more of the following criteria (from pathologic analysis of the radical 
prostatectomy specimen) check all that apply: 
 
a. 
Pathologic Gleason’s sum of equal or greater than 8. 
 
b. 
pT3b (seminal vesicle) or pT4 or N1.   
 
c. 
Pathologic Gleason’s sum of 7 and positive margin. 
 
d. 
Patients who have either a preoperative serum PSA value of > 15 ng/ml, 
or a biopsy Gleason score > 7, or a serum PSA level of > 10 ng/ml and a 
biopsy Gleason score > 6 are eligible. 
 
5.2 
Serum testosterone must be obtained within 28 days prior to registration. 
 
5.3 
Patients must have a performance status of 0 - 1 by Southwest Oncology Group criteria 
(see Section 10.3). 
 
5.4 
Prior neoadjuvant hormonal therapy (of ≤ 4 months duration) prior to radical 
prostatectomy is allowed provided that the patient has fulfilled the clinical eligibility criteria 
prior to hormonal treatment.  Patients may have started hormonal therapy post-
prostatectomy but prior to registration to this study (see Sections 5.2 and 5.5 for other 
requirements).   
 
No other therapy aimed at the treatment of this diagnosis may have been given or may 
be planned while the patient is receiving protocol treatment.  The use of low dose 
megace (< 40 mg/day) for the treatment of hot flashes is allowed.   
 
Patients must not have received prior radiation therapy.  If the treating physician wishes 
to have RT administered, then the patient should be registered to the study FIRST and 
then optional RT can be given on protocol.  All RT should be documented on the S9921 
Treatment Form (Form #38859). 
 


 
 
S9921 
 
 
Page 14a 
 
 
Revised 4/1/02 
 
Amended 2/14/06 
 
Revised 4/3/06 
 
 
 
 
 
SWOG Patient No.   
 
 
Patient's Initials (L, F, M)   
 
 
5.5 
a. 
Patients who have not started post-surgical hormone therapy:  Patients 
must have a post-operative serum prostate specific antigen (PSA) less than or 
equal to 0.2 ng/ml documented after surgery and within 28 days prior to 
registration. 
 
b. 
Patients who have already started post-surgical hormone therapy:  Patients 
must have a post-operative serum prostate specific antigen (PSA) ≤ 0.2 ng/ml 
documented after surgery, but prior to the start of hormonal therapy.  This may 
have been more then 28 days prior to registration. 
 
c. 
Patients who started hormone therapy prior to prostatectomy:  Patients 
must have a post-operative serum prostatic specific antigen (PSA) ≤ 0.2 ng/ml 
documented after surgery but prior to the start of post-surgical hormone therapy.  
This may have been more than 28 days prior to registration. 
 
5.6 
The institutional pathology report documenting eligibility for this study must be available 
for submission as outlined in Section 14.6. 
 
5.7 
All patients registered on or after June 15, 2006 must be offered the opportunity to 
consent for specimen banking per Section 15.0. 
 
 
 


Revised 4/15/00 
S9921 
Amended 7/1/00 
Page 15 
 
Amended 2/14/06 
 
 
 
 
SWOG Patient No.   
 
 
Patient's Initials (L, F, M)   
 
 
5.8 
Patients with PSA at clinical diagnosis ≥ 20 ng/ml must have a bone scan not suggestive 
of metastatic disease done within 180 days prior to registration.  
 
5.9 
Patients with symptoms of distant metastatic disease must have appropriate tests to 
evaluate for metastatic disease within 56 days prior to registration.  Patients with 
confirmed distant metastatic disease are ineligible. 
 
5.10 
Patients must have a baseline EKG to rule out underlying cardiac disease within 42 days 
prior to registration.  Patients with a history of cardiac disease, specifically CHF are 
ineligible unless their disease is well-controlled and they have LVEF ≥ 50% by MUGA or 
2-d echo within 42 days prior to registration. 
 
5.11 
Patients known to be HIV positive are not eligible because of the potential to confound 
the study's endpoint, although patients will not routinely be screened for HIV. 
 
5.12 
No other prior malignancy is allowed except for the following: adequately treated basal 
cell or squamous cell skin cancer, adequately treated Stage I or II cancer from which the 
patient is currently in complete remission, or any other cancer from which the patient has 
been disease-free for 5 years. 
 
5.13 
If Day 28, 42, 56, 120 or 180 falls on a weekend or holiday, the limit may be extended to 
the next working day. 
 
In calculating days of tests and measurements, the day a test or measurement is 
done is considered Day 0.  Therefore, if a test is done on a Monday, the Monday 
four weeks later would be considered Day 28.  This allows for efficient patient 
scheduling without exceeding the guidelines. 
 
5.14 
All patients must be informed of the investigational nature of this study and must sign and 
give written informed consent in accordance with institutional and federal guidelines. 
 
5.15 
At the time of patient registration, the treating institution's name and ID number must be 
provided to the Data Operations Center in Seattle in order to ensure that the current 
(within 365 days) date of institutional review board approval for this study has been 
entered into the data base. 
 


Revised 5/15/00 
S9921 
Revised 4/1/02 
Page 16 
 
Amended 2/14/06 
 
 
 
 
6.0 
STRATIFICATION FACTORS/RANDOMIZATION SCHEME 
 
6.1 
At the time of registration, patients will be randomly assigned to either Arm 1 or Arm 2 
according to a dynamic allocation scheme.  The treatment arms will be balanced with 
respect to the following factors: 
 
a. 
Pathologic stage of disease:   
 
1. 
organ confined (pT2a - pT2b with either ± surgical margins), but N0, 
 
2. 
not organ confined (≥ pT3), but N0, 
 
3. 
N1 (any T). 
 
b. 
Gleason’s sum:  < 7, 7, > 7. 
 
c. 
RT planned:  Yes vs. No. 
 
 
7.0 
TREATMENT PLAN 
 
For chemotherapy treatment or dose modification related questions, please contact Dr. L. 
Michael Glode at 303/724-3853 or Dr. Maha H. Hussain at 734/936-8906.  For urology related 
questions, please contact Dr. David P. Wood, Jr. at 734/763-9269.  For radiation therapy related 
questions, please contact Dr. Gregory P. Swanson at 210/616-5648.  For dosing principles or 
questions, please consult the Southwest Oncology Group Policy #38 "Dosing Principles for 
Patients on Clinical Trials" at http://swog.org (then click on "Policies and Manuals" under the 
"Visitors" menu and choose Policy 38). 
 
7.1 
Good Medical Practice 
 
The following pre-study tests should be obtained within 28 days prior to registration and 
the following guidelines should be met in accordance with good medical practice.  
Results of these tests do not determine eligibility and minor deviations would be 
acceptable if they do not impact on patient safety in the clinical judgement of the treating 
physician.  The Study Coordinator must be contacted if there are significant deviations in 
the values of these tests. 
 
a. 
Patients should have AGC ≥ 1,500 cells/mm3, and platelet count ≥ 100,000 
cells/mm3, SGOT ≤ 2.5 X institutional upper limits of normal and serum bilirubin 
≤ institutional upper limit of normal done within 28 days prior to registration. 
 
b. 
Patients must have recovered from major infections and/or surgical procedures 
and, in the opinion of the investigator, not have significant active concurrent 
medical illness precluding protocol treatment or survival. 
 
It is recommended that patients have a lymph node dissection in conjunction with the 
radical prostatectomy within 120 days prior to registration. 
 
7.2 
Patients will be randomized to: 
 
Arm 1:  Casodex® + Zoladex® for two years. 
 
Arm 2:  Chemotherapy (mitoxantrone + prednisone) x 6 cycles plus Casodex® + 
Zoladex® x 2 years. 
 
 


 
S9921 
 
Page 16a 
 
Revised 4/1/02 
 
Amended 2/14/06 
 
 
 
 
7.3 
Arm 1 - Hormonal therapy  
 
a. 
Zoladex 10.8 mg depot given subcutaneously once every 3 months (13 weeks) 
for a total of 8 injections given over 2 years, concurrent with Casodex 50 mg 
orally once daily everyday for two years. 
 
b. 
Neo-adjuvant or adjuvant hormonal therapy started prior to registration may be 
counted as protocol treatment if it included an LHRH agonist (e.g., goserelin 
acetate, leuprolide acetate, triptorelin) and there was no interruption in treatment.  
This could be either an LHRH agonist alone or in combination with antiandrogen, 
but antiandrogen alone will not be counted as pre-registration protocol treatment.  
Patients must receive a total of 2 years of treatment with LHRH agonist, where 
the treatment duration of any LHRH agonist received prior to registration may be 
counted as part of the 2 years of protocol treatment only if that treatment duration 
was continuous up to the date of registration.  It is recommended that patients 
also complete 2 years of concurrent antiandrogen treatment, but if LHRH agonist 
was started alone prior to registration the duration of antiandrogen treatment can 
be shortened to the remaining time of hormonal deprivation after starting the 
protocol.  For patients beginning LHRH agonist prior to registration, every effort 
should be made to conform to the LHRH agonist administration schedule that is 
specified in the study calendar, which may mean administering a few doses of 
single-month depot at the beginning to get on track.  All prior hormonal therapy 
must be documented on the S9921 Local Prostate Carcinoma Prestudy (Form # 
23968). 
 
Treatment Schedule 
 
 
 
 
ReRx 
Agent 
Dose 
Route 
Days 
Interval 
 
LHRH Agonist: 
Goserelin acetate 
10.8 mg 
SC 
1 
q 3 months 
(Zoladex®) 
 
 
 
(13 weeks) x 8 
 
Anti-androgen: 
Bicalutamide 
50 mg 
Oral 
1-730 (2 years) 
(Casodex®) 
 
(once daily) 
 
 
 
 
 
 
All continuous hormonal treatment counts towards protocol treatment. 
 


Revised 4/15/00 
Revised 7/1/01 
S9921 
Revised 1/1/01 
Amended 2/14/06 
Page 17 
 
 
Revised 4/3/06 
 
 
 
 
7.4 
Arm 2 Mitoxantrone and Prednisone + Hormonal Therapy 
 
The administration of Casodex + Zoladex + mitoxantrone + prednisone will commence 
simultaneously. 
 
a. 
Hormonal therapy: Follow same guidelines as Arm 1. 
 
b. 
Mitoxantrone 12 mg/m2 intravenously every 21 days, plus prednisone 5 mg/dose, 
BID orally given Days 1-21.  A total of 6 courses will be administered.  At the end 
of prednisone treatment (21 days after last mitoxantrone dose), prednisone 
should be tapered over 2 - 3 weeks at the discretion of the treating physician. 
 
NOTE:  Protocol treatment on Arm 2 is not considered complete until patients have 
completed the 2 years of hormonal therapy.  Do not submit an Off Treatment Notice until 
patient is off all protocol treatment. 
 
Agent 
Dose 
Route 
Days 
Interval 
 
Mitoxantrone 
12 mg/m2  
IV  
1 
q 21 days X 6 
 
 
over 30 min 
 
Prednisone 
5 mg/dose, BID 
Oral 
1 - 21 
continuous  
 
 
 
 
q 21 days x 6 
 
 
7.5 
Radiation Therapy: 
 
All RT must be recorded on the S9921 Treatment Form (Form #38859). 
 
Radiation therapy will begin upon recovery from chemotherapy (ideally 3 - 6 weeks and no 
later than 8 weeks) for patients on Arm 2, and should begin no later than 4 weeks after the 
initiation of androgen ablation for patients on Arm 1. 
 
Radiation therapy for patients on either arm of the study will be allowed at the physician's 
discretion following these suggested guidelines: 
 
Doses:  The target volume will be the prostate fossa and immediate periprostatic tissue.  The 
minimum and maximum allowable doses will be 6,480 cGy and 7,100 cGy respectively at a 
dose of 180 - 200 cGy per day.  Conedown of the fields at 4,400 - 4,600 cGy is allowed (see 
portals below). 
 
Radiation Portals:  Whole pelvis radiation is not allowed.  Initial ports can have more generous 
margins than those outlined below, but after the initial 4,400 - 4,600 cGy should be coned 
down to those margins.  The goal is to treat the prostate fossa.  Treatment of the seminal 
vesicle (SV) fossa is left to the discretion of the treating physician.  For SV negative patients it 
is probably not necessary.  For SV positive patients, it is usually the base of the seminal 
vesicle that is involved and it may not be desirable to cover the whole SV fossa to the full dose 
out of concerns for toxicity.  If a preoperative CT is available, it can be used in planning, with a 
margin of 1.5 cm around the prostate and if treated, the SV.  For simulation, rectal and 
urethral or bladder contrast is required.   
 
Four-field technique (recommended) can be planned with 3D conformal technique.  IMRT is 
allowed as long as boundary parameters are met.  The NCI's IMRT guidelines can be found 
on the Advanced Technologies Consortium website (http://atc.wush.edu under "News", then 
"NCI IMRT Letter"). 
 
AP/PA ports:   
 
Inferior margin will be at or below the ischial tuberosity (or if urethrogram is used, > 0.5 
cm below the narrowing of the urethra).  
 
Lateral margin will be minimum of 1.0 cm lateral to the midpoint of the obturator foramen 
(usually a field width of 8 to 9 cm). 
 
Superior margin for prostate only or to include the base of the SV is 2 cm above the 
pubic symphysis.  For the entire SV is at the top of the femoral head. 
 


Revised 4/15/00 
S9921 
Amended 2/14/06 
Page 18 
 
 
 
 
 
Lateral ports: 
 
Inferior margins as for the AP/PA ports.   
 
Lateral margins - anterior:  1 cm anterior to the junction of the projection of the posterior 
pubic symphysis over the superior ramus of the pubis or at the tip of the pubic 
symphysis.   
 
Posterior:  1 cm posterior to a line from the posterior acetabulum and posterior obturator 
foramen.  As much rectum as possible needs to be spared, but at the minimum the 
anterior 1 cm will be included in the port.  This would usually put the block in the mid 
rectum.  A larger portion of the rectum may need to be covered if the rectum subluxed 
into the prostate fossa.  The rectum above the midpoint of the femoral head can be 
blocked entirely. 
 
Superior:  margins for the prostate only and base of the SV would be as for the AP/PA 
ports.  The anterior bladder can be blocked from a line 1 cm anterior to the junction of the 
projection of the pubic symphysis over the superior ramus of the pubis through the center 
of the femoral head.  Unless the entire SV fossa is to be covered the area posterior to the 
acetabulum can be blocked. 
 
Beam Energy:  Megavoltage equipment with effective photon energies greater than 6 MV 
is required. 
 
Treatment Distance:  Minimum SSD and SAD distance is 80 cm. 
 
Fractionation:  180 - 200 cGy per day five days a week with one set of portals treated 
each day. 
 
Treatment Planning:  Isodose distribution at the mid-transverse plane of the tumor 
volume and the central axis (if different). 
 
Localization films: If a cone down is done, both fields can be on the same set of films if 
they are the basis for both treatment.  
 
a. 
Patients will be evaluated weekly for toxicity during radiotherapy and all toxicities 
documented on the S9921 Adverse Event Summary Form (Form #27242). 
 
b. 
Post radiation follow-up:  Follow-up will be in accordance with the Study 
Calendar. 
 
c. 
Radiotherapy information will be recorded on the S9921 Treatment Form (Form 
#38859).   
 
7.6 
There is a tumor bank for this study for patients with adequate tissue available.  In order 
to have tissue submitted, patients must consent to submission of tissue.  Please see 
Section 15.0 for details of tissue submission. 
 
7.7 
Criteria For Removal From Protocol Treatment 
 
a. 
Unacceptable toxicity. 
 
b. 
Completion of 2 years of hormonal therapy per protocol. 
 
c. 
The patient may withdraw from the study at any time for any reason.   
 
d. 
Disease progression. 
 
7.8 
All reasons for discontinuation of treatment must be documented in the Off Treatment 
Notice (Form #8756). 
 
7.9 
All patients will be followed 15 years or until death. 


 
S9921 
 
Page 19 
 
Amended 2/14/06 
 
 
 
 
8.0 
TOXICITIES TO BE MONITORED AND DOSAGE MODIFICATIONS 
 
8.1 
Patients will be evaluated and graded for toxicity every visit as specified on the Study 
Calendar for subjective/objective evidence of developing toxicities according to the NCI 
Common Toxicity Criteria version 2.X (see Section 19.1). 
 
8.2 
Arm 1 – Hormone therapy  
 
a. 
There are no dosage adjustments for hematologic toxicity. 
 
b. 
The most common side effects of anti-androgen therapy are breast pain and 
gynecomastia.  No dose modification is needed except in very severe cases 
(Grade 3 or higher).  In such cases, the anti-androgen will be discontinued 
permanently and LHRH agonist therapy continued.   
 
c. 
Antiandrogens may be omitted in the case of hepatic toxicity of any severity (at 
the discretion of the treating physician). 
 
d. 
Hot flashes may develop in patients treated with LHRH agonists.  In general, 
these will not require therapy as resolution is expected following completion of 
protocol treatment (termination of therapy).  
 
8.3 
Arm 2 – Mitoxantrone and prednisone + hormone therapy (follow guidelines in Section 
8.2 for toxicities attributable to hormone therapy).  If mitoxantrone is delayed due to 
toxicity, prednisone is given on schedule without dose reduction. 
 
a. 
Myelosuppression: 
 
See table below for a summary of dose modifications for myelosuppression. 
 
Grade 1, 2 and 3 myelosuppression (leukopenia, neutropenia, thrombo-
cytopenia) and Grade 4 leukopenia or Grade 4 neutropenia except as defined 
below, with recovery within twenty-one days, does not require dose modification.  
Patients who do not recover WBC or platelet counts to ≤ CTC Grade 1 toxicity 
within 21 days should be reduced to dose level -1 for all subsequent courses. 
 
In order to maximize dose intensity, patients with afebrile Grade 4 neutropenia ≥ 
7 days or Grade 3 or 4 neutropenia associated with fever (one reading of oral 
temperature > 38.5°C, or three readings of oral temperature > 38.0°C in a 24-
hour period) should be retreated after recovery at the dose level -1. 
 
Grade 4 thrombocytopenia (platelet count < 25,000) at any time necessitates 
retreatment after recovery at the dose level -1. 
 
G-CSF is not permitted. 
 
Dose Modifications for Myelosuppression. 
 
 
 
Dose Level 
Mitoxantrone Dose (mg/m2) 
 
 
Starting Level 
12 
 
Level -1* 
9 
 
*This is a permanent dose reduction.  Further dose reduction requires removing 
patient from protocol treatment. 
 


 
S9921 
 
Page 20 
 
Revised 4/15/00 
 
Revised 4/1/02 
 
Amended 2/14/06 
 
 
 
 
b. 
Gastrointestinal 
 
Appropriate symptomatic treatment of nausea and/or emesis, diarrhea, 
mucositis, and/or abdominal pain is permitted. 
 
c. 
Cardiovascular 
 
The total cumulative dose of mitoxantrone is anticipated to ≤ 72 mg/m2; based on 
6 cycles of 12 mg/m2; EKG changes, arrhythmias, tachycardia, and/or chest pain 
should be managed based on the specific findings.  Patients who have 
underlying cardiac disease or CHF, will undergo baseline ejection fraction 
determination echocardiogram or MUGA and this evaluation will be repeated for 
all patients every two courses.  If MUGA decreases to below institutional limits 
(or < 15%) discontinue protocol treatment. 
 
d. 
Allergic: 
 
Patients who experience Grade 3 or 4 hypotension, urticaria, or severe rash 
should be removed from protocol treatment. 
 
e. 
Hepatic (≥ Grade 2): 
 
Delay mitoxantrone treatment for up to 4 weeks until transient increases in 
SGOT or hyperbilirubinemia have resolved to Grade 1 or less.  If toxicity has not 
resolved within 4 weeks discontinue protocol treatment. 
 
f. 
Other: 
 
If toxicities ≤ Grade 2, manage symptomatically, if possible and retreat without 
dose reduction. 
 
If toxicities ≥ Grade 3, drug should be withheld (except for alopecia or anemia) 
until resolution to ≤ Grade 1 or baseline if baseline was greater than Grade 1, 
then reinstituted, if medically appropriate, at a dose of 9 mg/m2 (permanent dose 
reduction). 
 
8.4 
For chemotherapy treatment or dose modification related questions please contact Dr. 
Glode at 303/724-3853 or Dr. Hussain at 734/936-8906.  For urology related questions 
please contact Dr. Wood at 734/763-9269.  For radiation therapy related questions 
please contact Dr. Swanson at 210/616-5648. 
 
8.5 
Unexpected or fatal toxicities (including suspected reactions) must be reported to the 
Operations Office, to the Study Coordinator, to the IRB and the NCI.  The procedure for 
reporting adverse reactions is outlined in Section 16.0. 
 


S9921
Page 21
Revised 4/15/00
Amended 2/14/06
9.0    STUDY CALENDAR
9.1  Arm 1   Hormonal therapy alone
Ω
REQUIRED STUDIES
PRE
Mo
Mo
Mo
Mo
Mo
Mo
Mo
Mo
STUDY
1
4
7
10
13
16
19
22
PHYSICAL
History and Physical Exam  
X
X
X
X
X
X
X
X
Weight and Performance Status
X
X
X
X
X
X
X
X
Toxicity Notation
X
X
X
X
X
X
X
X
LABORATORY / TESTS
PSA   ¥
X
X
X
X
X
X
X
X
CBC/diff/platelets  
X**
Bilirubin
X**
SGOT
X**
Testosterone ¥
X
X
X
X
Blood specimens   π
X
X
Tissue Specimen ™
X
X-RAYS AND SCANS
Bone Scan   §
X
CT/MRI abdomen and pelvis    ∑
X
OTHER X-RAYS/SCANS
EKG
X
MUGA or 2-d Echo  
X*
TREATMENT (Sect. 7.0)
Radical Prostatectomy  ∞ 
X
 
Goserelin acetate (Zoladex®) #
X
X
X
X
X
X
X
X
Bicalutamide (Casodex®) √
X
X
X
X
X
X
X
X
NOTE: All forms to be used for this study are found in Section 18.0. Form submission
guidelines are found in Section 14.0.
**  Results of these tests do not determine eligibility but should be done prior to registration in accordance
     with good medical practice (see Section 7.1a).  With the exception of blood counts,  significant deviations 
     in the values of these tests should be discussed with the Study Coordinator.
     These tests are required during treatment as scheduled to assess toxicity.
π   Blood specimens for patients opting to participate in the blood and tissue banking should be collected prestudy, 
       between Weeks 24 and 28, and at progression (see Section 15.0).
∑   See Section 5.9.  CT scan of abdomen and pelvis must be performed if patient has symptoms of distant 
     metastatic disease.
#   Every 3 months.
√   Daily.
Ω  Treatment and parameters will continue for a total of two years according to the schedule outlined above.
     After off treatment, patients will be followed for disease status with Physical Exam and DRE (if PSA ≥ 0.1 ng/ml),
     repeated at end of treatment and  every six months for two years and annually thereafter
     for three additional years.  All patients will be followed for 15 years or until death, and PSA will be collected 
     as noted below.
*   At prestudy, only for patients with underlying cardiac disease or CHF.
§   For patients with PSA ≥ 20 ng/ml at diagnosis.
∞   Must be done within 120 days prior to registration.
™ For patients with adequate tissue and who consent to tissue banking (see Section 15.0 for details).
¥   Testosterone is collected every six months until it reaches the institutional lower limit of normal (ILLN).  
      PSA is collected every three months for five years, and then every 6 months until 15 years or death.


S9921
Page 22
Revised 4/15/00
Revised 1/1/01
Revised 7/1/01
Amended 2/14/06
9.0    STUDY CALENDAR
9.2  Arm 2   Hormonal therapy + mitoxantrone + prednisone
Cy 1
Cy 2
Cy 3
Cy 4
Cy 5
Cy 6
Ω
REQUIRED STUDIES
PRE
Mo
Mo
Mo Mo Mo Mo Mo Mo
STUDY
1
Day Day Day Day Day Day Day Day
4
Day Day
7
10
13
16
19
22
 
15
22
36
43
57
64
78
85
99 106
PHYSICAL
History and Physical Exam  
X
X
X
X
X
X
X
X
X
X
X
X
Weight and Performance Status
X
X
X
X
X
X
X
X
X
X
X
X
Toxicity Notation
X
X
X
X
X
X
X
X
X
X
X
X
X
LABORATORY / TESTS
PSA   ¥
X
X
X
X
X
X
X
X
CBC/diff/platelets
X**
X
X
X
X
X
X
X
X
X
X
Bilirubin
X**
X
X
X
X
X
X
X
X
X
X
SGOT
X**
X
X
X
X
X
X
X
X
X
X
Testosterone  ¥
X
X
X
X
Blood specimens   π
X
X
Tissue Specimen  ™
X
X-RAYS AND SCANS
Bone Scan   § 
X
CT/MRI abdomen and pelvis   ∑
X
OTHER X-RAYS/SCANS
EKG
X
MUGA or 2-d Echo
X*
X*
X*
TREATMENT (Sect. 7.0)
Radical Prostatectomy  ∞ 
X
 
Mitoxantrone ¶
X
X
X
X
X
X
Prednisone ƒ
X
X
X
X
X
X
 
 
Goserelin acetate (Zoladex®) #
X
X
X
X
X
X
X
X
Bicalutamide (Casodex®)√
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
NOTE: All forms to be used for this study are found in Section 18.0. Form submission
guidelines are found in Section 14.0.
**  Results of these tests do not determine eligibility but should be done prior to registration in accordance  with good medical practice 
    (see Section 7.1a).   With the exception of blood counts, significant deviations in the values of these  tests should be discussed
    with the Study Coordinator.   These tests are required during treatment as scheduled to assess toxicity.
π   Blood specimens for patients opting to participate in the blood and tissue banking should be collected prestudy, between Weeks 24
       and 28, and at progression (see Section 15.0).
∑   See Section 5.9.  CT scan of abdomen and pelvis must be performed if patient has symptoms of distant metastatic disease. 
¶   Mitoxantrone will be given on Day 1, every twenty-one days for six cycles.
ƒ   Prednisone will be given twice a day continuously for 6 twenty-one day cycles.  At the end of prednisone treatment (21 days 
     after last mitoxantrone dose), prednisone should be tapered over 2 - 3 weeks at the discretion of the treating physician.
#   Every 3 months.
√   Daily.
Ω  Treatment and parameters will continue for a total of two years according to the schedule outlined above.
     After off treatment, patients will be followed for disease status with Physical Exam and DRE (if PSA ≥ 0.1 ng/ml), repeated at end
       of treatment and  every six months for two years and annually thereafter for three additional years.  All patients will be followed
       for 15 years or until death, and PSA will be collected as noted below.
*   At prestudy, only for patients with underlying cardiac disease or CHF.  Follow-up MUGA or 2-d echo is only needed for those
     patients who required one at baseline.
§   For patients with PSA ≥ 20 ng/ml at diagnosis.
∞   Must be done within 120 days prior to registration.
™  For patients with adequate tissue and who consent to tissue banking (see Section 15.0 for details).
¥   Testosterone is collected every six months until it reaches the institutional lower limit of normal (ILLN).  
      PSA is collected every three months for five years, and then every 6 months until 15 years or death.


 Amended 9/12/03 
 
S9921 
Amended 2/14/06 
Page 23 
 
 
 
 
10.0 
CRITERIA FOR EVALUATION AND ENDPOINT DEFINITIONS 
 
10.1 
Overall Survival:  Measured from date of randomization to date of death from any cause.  
Patient known to be alive are censored at date of last contact. 
 
10.2 
Disease-Free Survival:  Measured from date of randomization to date of first observation 
of recurrence or death due to any cause.  Patients without recurrence are censored at 
date of last contact. 
  
10.3 
Performance Status:  Patients will be graded according to the current Southwest 
Oncology Group grading scale: 
 
GRADE 
SCALE 
 
0 
Fully active; able to carry on all predisease activities without 
restriction.   
 
1 
Restricted in physically strenuous activity but ambulatory and 
able to carry out work of a light or sedentary nature, e.g., light 
housework, office work.   
 
2 
Ambulatory and capable of all self-care but unable to carry out 
any work activities.  Up and about more than 50% of waking 
hours.   
 
3 
Capable of only limited self-care; confined to bed or chair more 
than 50% of waking hours.   
 
4 
Completely disabled.  Cannot carry on any self-care.  Totally 
confined to bed or chair.   
 
5 
Dead 
 
10.4 
PSA Progression:  A serum PSA level of > 0.2 ng/mL measured on 3 consecutive 
occasions or in the absence of increasing PSA, a positive bone scan result or other 
radiographic or histologic evidence of progression will be used.  Date of progression will 
be the date that the first measure of increasing PSA is noted in the series of 3.  (40) 
 
10.5 
PSA Progression-Free Survival:  Measured from date of randomization to date of PSA 
progression or death due to any cause. 
 
 
11.0 
STATISTICAL CONSIDERATIONS 
 
11.1 
The primary objective of this study is to compare the overall survival in prostate cancer 
patients treated with combined androgen blockade (LHRH agonist and anti-androgen) 
with that in patients treated with the combination of combined androgen blockade and 
mitoxantrone plus prednisone.  Mitoxantrone, prednisone and combined androgen 
blockade would be judged superior to the standard regimen of combined androgen 
blockade if the true increase in median survival is 30%.   
 
11.2 
It was initially anticipated that 250 eligible patients per year would be accrued to this 
study.  However, accrual has been slower than expected.  Instead of the original accrual 
period estimate of 5.5 years, we now anticipate a period of 9.5 years in order to 
randomize 680 eligible patients per arm. 
 
11.3 
A median survival of 10 years is anticipated on combined androgen blockade.  Assuming 
exponential survival, 9.5 years of patient accrual, and an additional 4 years of follow-up, 
a sample size of 680 patients per arm, this study has .92 power to detect a 30% increase 
in median survival, using a one-sided test with 0.05 significance level. 
 
11.4 
This study will be monitored throughout the accrual and follow-up periods by the 
Southwest Oncology Group Data and Safety Monitoring Committee (DSMC).  The DSMC 
will be approved by CTEP and will include members both from within the Group and from 
outside the Group.  A majority of the DSMC will be outside members, and at least one 
outside member will be a patient advocate and at least one will be a statistician.  The 


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Group Statistician and two representatives of CTEP will be non-voting members.  The 
Group Chair may not be on the DSMC.  The DSMC will be provided with administrative 
reports every 6 months by the Study Statistician, and will discuss the reports if necessary 
at a meeting held in conjunction with the Southwest Oncology Group Meeting.  The 
DSMC and study statistician will be the only individuals with regular access to the 
primary outcome data and this information will be provided to the DSMC on a regular 
basis. 
 
11.5 
In addition to the study monitoring mentioned above, three formal interim analyses will be 
done.  The decision to terminate accrual early will be made by the DSMC, and will 
consider disease-free survival, toxicities, and other factors in addition to survival.  
Additionally, the Southwest Oncology Group Statistical Center will closely monitor 
throughout the trial whether there is differential use of optional radiotherapy between the 
two treatment groups and this information will be provided to the DSMC at regular 
intervals. 
 
11.6 
The first formal interim analysis will be done after 700 patients have been entered, 
approximately 6 years after the study opens.  Evidence suggesting early termination of 
the trial would be if the alternative hypothesis of a 30% improvement in survival with the 
MP + CZ combination arm is rejected at the 0.005 level, using an extension of the 
logrank test that allows for testing a relative risk not equal to 1.  In addition, the null 
hypothesis of no difference in survival will be tested at the one-sided level of 0.005.  The 
second interim analysis will be performed after 50% of the total expected deaths (275 
deaths) will have occurred.  Testing will be done as above at the 0.005 level.  A third 
interim analysis will be performed 2.5 years after accrual has been completed.  This 
testing will also be done at the alpha=0.005 level.  The final analysis will be performed at 
the 0.045 significance level, approximately 4 years after accrual has been completed. 
 
11.7 
Secondary analyses will also be done regarding disease-free survival and toxicities.  
With 680 patients per arm, toxicity rates can be estimated to within at ± 4% (95% 
confidence interval). 
 
 
12.0 
DISCIPLINE REVIEW 
 
There will be no discipline review for this study. 
 
 
13.0 
REGISTRATION GUIDELINES 
 
13.1 
Patients must be registered prior to initiation of protocol treatment (no more than ten 
working days prior to planned start of treatment). 
 
13.2  
For either phone or web registration, the individual registering the patient must have 
completed the appropriate Southwest Oncology Group Registration Form. The 
completed form must be referred to during the registration but should not be submitted as 
part of the patient data. 
 
The individual registering the patient must also be prepared to provide the treating 
institution's name and ID number in order to ensure that the current (within 365 days) 
date of institutional review board approval for this study has been entered into the data 
base.  Patients will not be registered if the IRB approval date has not been provided or is 
> 365 days prior to the date of registration. 
 


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13.3 
Registration Procedures 
 
a. 
You may register patients from Member, CCOP, UCOP and approved 
Affiliate institutions to a therapeutics study using the SWOG 
Registration program. To access the Registration program go to the 
SWOG Web site (http://swog.org) and click on the Logon link to go to 
the 
SWOG 
Members 
Area 
logon 
page 
(https://swog.org/visitors/logon.asp).  This Web program is available 
at any time except for periods listed under Down Times.  Log on as 
an Individual User using your SWOG Roster ID Number and 
individual web user password.  Help for the logon process may be 
found at https://swog.org/visitors/logonhelp.asp. After you have 
logged on, click on the Clinical Trials link and then the Patient Reg 
link to go to the Entry Page for the Patient Registration program. If 
you are a Registrar at an institution with Internet access you are 
encouraged to register this way.  For new users, the link to a "Starter 
Kit" of help files may be found by clicking on Starter Kit link at the 
logon page. 
 
To register a patient the following must be done (in order): 
 
1. 
You are entered into the Southwest Oncology Group Roster 
and issued a SWOG Roster ID Number,  
 
2. 
You are associated as an investigator or CRA/RN to the 
institution where a registration is occurring, and  
 
 
3. 
You are granted permission to use the Patient Registration 
program at that institution.  
 
 
For assistance with points 1 and 2 call the SWOG Operations Office 
at 210/677-8808. For point 3 you must contact your Web User 
Administrator.  Each SWOG institution has one or more Web User 
Administrators who may set up Web Users at their institution and 
assign permissions and passwords to these users. For other 
password problems or problems with the Patient Registration 
program, please e-mail webreghelp@crab.org. Include your name, 
Roster ID Number, and telephone number, when the problem 
occurred, and exactly what you were doing. 
 
4. 
If the Web Reg program is not used, the registration must be 
done by phone. 
 
Member, Affiliate, CCOP, and UCOP Institutions 
 
Registration by phone of patients from member, affiliate and CCOP 
institutions must be done through the Southwest Oncology Group 
Data Operations Center in Seattle by telephoning 206/652-2267, 6:30 
a.m. to 4:00 p.m. Pacific Time, Monday through Friday, excluding 
holidays. 
 
 


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13.4 
CALGB Institutions:  Confirm all eligibility criteria as listed in Section 5.0.  Registration will 
be accepted through institutions with direct registration privileges.  Call the CALGB 
Registrar (919/286-4704, Monday - Friday, 9:00 AM - 4:30 PM, Eastern Time) with the 
following information: 
 
Study 
Name of Group (CALGB) 
Name of institution where patient is being treated 
Name of treating physician 
Naming of treating physician or responsible CRA 
CALGB patient ID#, if applicable  
Patient's first name, middle initial, and last name 
Patient's Social Security number, date of birth and hospital ID number 
Patient's gender 
Patient's height, in centimeters 
Patient's weight, in kilograms 
Patient's race 
CTC performance status (optional, if required by CDUS) 
Type of insurance (method of payment) 
Disease, type and stage, if applicable 
Patient's Postal Code, if applicable 
Treatment start date 
Date of signed consent 
Eligibility criteria met (yes, no) 
Stratification factors (Surgical extent of disease, Gleason Sum, RT planned; see Section 
6.1) 
 
The CALGB Registrar will then contact the Southwest Oncology Group Statistical Center 
for treatment assignment, after which the CALGB Registrar will inform the institution of 
the treatment assignment.  The Southwest Oncology Group will forward a confirmation of 
treatment assignment to the CALGB Registrar, who will subsequently forward the 
confirmation of treatment assignment to the main member institution. 
 
Patients entered on this study may not be cancelled (see Section 13.6). 
 
13.5 
CTSU REGISTRATION/RANDOMIZATION 
 
Prior to the recruitment of a patient for this study, investigators must be registered 
members of the CTSU.  Each investigator must have an NCI investigator number and 
must maintain an “active” investigator registration status through the annual submission 
of a complete investigator registration packet (FDA Form 1572 with original signature, 
current CV, Supplemental Investigator Data Form with signature, and Financial 
Disclosure Form with original signature) to the Pharmaceutical Management Branch, 
CTEP, DCTD, NCI.  These forms are available on the CTSU registered member Web site 
or by calling the PMB at 301-496-5725 Monday through Friday between 8:30 a.m. and 
4:30 p.m. Eastern time. 
 
Each CTSU investigator or group of investigators at a clinical site must obtain IRB 
approval for this protocol and submit IRB approval and supporting documentation to the 
CTSU Regulatory Office before they can enroll patients.  Study centers can check the 
status of their registration packets by querying the Regulatory Support System (RSS) site 
registration status page of the CTSU member web site at http://members.ctsu.org. 
 
 
 


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Revised 2/1/07 
 
 
 
 
All forms and documents associated with this study can be downloaded from the S9921 
Web page on the CTSU registered member Web site (https://members.ctsu.org).  
Patients can be registered only after pre-treatment evaluation is complete, all eligibility 
criteria have been met, and the study site is listed as ‘approved’ in the CTSU RSS. 
 
Requirements for S9921 site registration: 
 
• 
CTSU IRB Certification 
• 
CTSU IRB/Regulatory Approval Transmittal Sheet 
 
Prestudy requirements for patient enrollment on S9921 
 
• 
Patient must meet all inclusion criteria, and no exclusion criteria should apply 
• 
Patient has signed and dated all applicable consents and authorization forms 
• 
All baseline laboratory tests and prestudy evaluations performed. 
 
CTSU Procedures for Patient Enrollment 
 
1. 
Contact the CTSU Patient Registration Office by calling 1-888-462-3009.  Leave 
a voicemail to alert the CTSU Patient Registrar that an enrollment is forthcoming. 
For immediate registration needs, e.g. within one hour, call the registrar cell 
phone at 1-301-704-2376. 
 
2. 
Complete the following forms: 
 
• 
CTSU Patient Enrollment Transmittal Form 
• 
Eligibility Criteria Checklist (Section 5.0 of the protocol) 
• 
SWOG Registration Form (Complete all sections of form except for SWOG-
specific data fields) 
 
3. 
Fax these forms to the CTSU Patient Registrar at 1-888-691-8039 between the 
hours of 8:00 a.m. and 8:00 p.m., Mon-Fri, Eastern Time (excluding holidays).  
The CTSU registrar will check the investigator and site information to ensure that 
all regulatory requirements have been met.  The registrar will also check that 
forms are complete and follow-up with the site to resolve any discrepancies. 
 
4. 
Once investigator eligibility is confirmed and enrollment documents deemed 
complete, the CTSU registrar will contact the Southwest Oncology Group to 
obtain assignment of a treatment arm and assignment of a unique patient ID (to 
be used on all future forms and correspondence).  The CTSU registrar will 
convey this information to the enrolling site and follow up with a confirmation via 
e-mail or fax. 
 
13.6 
For either method of registration, exceptions to Southwest Oncology Group registration 
policies will not be permitted. 
  
a. 
Patients must meet all eligibility requirements. 
 
b. 
Institutions must be identified as approved for registration. 
 
c. 
Registrations may not be cancelled. 
  
d. 
Late registrations (after initiation of treatment) will not be accepted. 


 
S9921 
 
Page 27a 
 
Revised 2/1/07 
 
 
 
 
 
 
14.0 
DATA SUBMISSION SCHEDULE 
 
14.1 
Data must be submitted according to the protocol requirements for ALL patients 
registered, whether or not assigned treatment is administered, including patients deemed 
to be ineligible.  Patients for whom documentation is inadequate to determine eligibility 
will generally be deemed ineligible. 
 
14.2 
Master forms are included in Section 18.0 and (with the exception of the sample consent 
form and the Registration Form) must be photocopied for data submission to the Data 
Operations Center in Seattle.  Alternatively, data from approved SWOG institutions may 
be submitted on-line via the web; see Section 14.3a for details. 
 


 
S9921 
 
Page 28 
 
Amended 2/14/06 
 
 
 
 
14.3 
Southwest Oncology Group Institutions 
 
Data Submission Procedures.  Please select one option for submitting specific data.  
Data submitted electronically or via facsimile should not be followed up with a mailed 
version. 
 
a. 
Southwest Oncology Group Member Institutions, CCOPs, UCOPs and approved 
Affiliate institutions may submit data electronically via the Web by using the 
SWOG CRA Workbench.  To access the CRA Workbench, go to the SWOG Web 
site (http://swog.org) and logon to the Members Area.   After you have logged on, 
click on the CRA Workbench link to access the home page for CRA Workbench 
website.  Next, click on the Data Submission link and follow the instructions.  If 
you are a CRA at an institution with Internet access, you are encouraged to 
submit data this way.  For new users, the link to a "Starter Kit" of help files may 
be found by clicking on the Starter Kit link at the Members" logon page. 
 
To submit data via the web the following must be done (in order): 
 
1. 
You are entered into the Southwest Oncology Group Roster and issued 
a SWOG Roster ID Number, 
2. 
You are associated as an investigator or CRA/RN at the institution where 
the patient is being treated or followed, and 
3. 
Your Web User Administrator has added you as a web user and has 
given you the appropriate system permissions to submit data for that 
institution. 
 
For assistance with points 1 and 2 call the Operations Office at 210/677-8808.  
For point 3, contact your local Web User Administrator (refer to the "Who is my 
Web User Administrator?" function on the swog.org Members logon page).  For 
other 
difficulties 
with 
the 
CRA 
Workbench, 
please 
email 
technicalquestion@crab.org. 
 
b. 
Alternatives to the CRA Workbench/web based data submission option are:  
submission via facsimile, surface, or express mail. 
 
For facsimile submission:  Member, CCOPs, UCOPs and approved Affiliate 
institutions may submit data via facsimile to 800/892-4007 or 206/342-1680 
locally.  Please do not use cover sheet for faxed data.  Facsimile submission is 
the 2nd preferred option for data submission. 
 
For surface or express mail:  Group Member Institutions, CCOPs, UCOPs and 
approved Affiliate institutions must submit one copy of all data forms directly to 
the Southwest Oncology Group Data Operations Center in Seattle at the address 
below.  Affiliates must submit (number of copies to be determined by the Group 
member) copies of all forms to their Group member institution for forwarding to 
the Southwest Oncology Group Data Operations Center in Seattle at the 
following address: 
 
Southwest Oncology Group Data Operations Center 
Cancer Research And Biostatistics 
1730 Minor Ave, STE 1900 
Seattle, WA  98101-1468 
 
 


 
S9921 
 
Page 28a 
 
Amended 2/14/06 
 
Revised 2/1/07 
 
 
 
 
14.4 
CALGB Institutions 
 
CALGB participants should submit data forms as listed in this section at the required 
intervals to: 
 
Southwest Oncology Group Data Operations 
Cancer Research And Biostatistics 
1730 Minor Avenue, Suite 1900 
Seattle, WA  98101-1468 
 
Include the Southwest Oncology Group protocol number and patient number, as well as 
the CALGB study number and patient number.   
 
14.5 
CTSU DATA SUBMISSION AND RECONCILIATION 
 
1. 
All case report forms (CRFs) associated with this study must be downloaded 
from the S9921 Web page located on the CTSU registered member Web site 
(https://members.ctsu.org).  Sites must use the current form versions and adhere 
to the instructions and submission schedule outlined in the protocol. 
 
2. 
Submit all completed CRFs (with the exception of patient enrollment forms), 
clinical reports, and transmittals directly to the Southwest Oncology Data 
Operations Office.  The preferred method of sending data is via fax at 800/892-
4007.  Do NOT include a cover sheet for faxed data. 
 
3. 
The Southwest Oncology Group Data Operations Office will send query notices 
and delinquency reports directly to the site for reconciliation.  Please fax query 
responses and delinquent data to the Southwest Oncology Group Data 
Operations Office and do not copy the CTSU Data Operations.  When faxing 
data, include the query sheet that was originally sent from the Southwest 
Oncology Group. 
 
4 
Each site should have a designated CTSU Administrator and Data Administrator 
and must keep their CTEP AMS account contact information current.  This 
will ensure timely communication between the clinical site and the Southwest 
Oncology Group Data Operations Office. 
 
14.6 
WITHIN 14 DAYS OF REGISTRATION: 
 
Submit copies of the following: 
 
S9921 Local Prostate Carcinoma Prestudy (Form #23968) 
 
Pathology Report 
 
14.7 
AFTER CYCLE 3 AND CYCLE 6 OF CHEMOTHERAPY FOR ARM 2: 
 
Submit copies of the S9921 Adverse Event Summary Form (Form #27242) and the 
S9921 Chemotherapy Treatment Form (Form #61544) summarizing adverse event and 
chemotherapy treatment information for the 3 cycles of chemotherapy being reported.   
 
 


 
S9921 
 
Page 28b 
 
Amended 2/14/06 
 
 
 
 
14.8 
EVERY THREE MONTHS WHILE ON PROTOCOL TREATMENT (INCLUDING 
HORMONAL THERAPY) FOR BOTH ARM 1 AND ARM 2: 
 
Submit the S9921 Adverse Event Summary Form (Form #27242) and the S9921 
Treatment Form (Form #38859).   
 
14.9 
EVERY THREE MONTHS FOR FIVE YEARS, THEN EVERY SIX MONTHS UNTIL 15 
YEARS OR DEATH: 
 
Submit the S9921 PSA Reporting Form (Form #59255). 
 
14.10 
EVERY SIX MONTHS UNTIL TESTOSTERONE LEVELS REACH INSTITUTIONAL 
LOWER LIMIT OF NORMAL (ILLN): 
 
Submit the S9921 Testosterone Reporting Form (Form #25939). 
 
14.11 
WITHIN 14 DAYS OF DISCONTINUATION OF ALL TREATMENT (INCLUDING 
HORMONAL THERAPY): 
 
Submit copies of the Off Treatment Notice (Form #8756), final S9921 Adverse Event 
Summary Form (Form #27242), and final S9921 Treatment Form (Form #38859). 
 
14.12 
AFTER OFF ALL PROTOCOL TREATMENT, EVERY SIX MONTHS FOR TWO YEARS 
AND ANNUALLY THEREAFTER: 
 
Submit the Follow-Up Form (Form #64587). 
 
14.13 
WITHIN 4 WEEKS OF KNOWLEDGE OF DEATH: 
 
Submit copies of the Notice of Death (Form #49467).  Also submit a final S9921 Adverse 
Event Summary Form (Form #27242) and S9921 Treatment Form (Form #38859) (if 
patient was still on protocol treatment) or Follow-Up Form (Form #64587) (if patient was 
off protocol treatment) documenting death information. 
 
 
15.0 
SPECIAL INSTRUCTIONS 
 
15.1 
Specimen Banking for Southwest Oncology Group Institutions 
 
a. 
Specimens Requested and Patient Consent 
 
It is strongly recommended that with the patient's additional consent on the 
"Consent Form for Use of Specimens for Research" that a formalin-fixed, 
paraffin-embedded tissue block from a representative area of the primary tumor 
be submitted as outlined in Section 15.1d below for banking. 
 
It is strongly recommended that with the patient's additional consent that blood 
specimens be obtained at pre-study (after registration, but prior to receiving first 
dose of treatment), between Weeks 24 and 28, and at progression for banking.  
Instructions for the processing of these specimens are found in Section 15.1c 
below.   
 
Material will be kept at the Southwest Oncology Group Repository. 
 


 
S9921 
 
Page 28c 
 
Amended 2/14/06 
 
 
 
 
b. 
General Specimen Submission Instructions  
 
1. 
Southwest Oncology Group Specimen Tracking System Guidelines 
 
All specimen submissions for patients registered on this study must be 
entered and tracked using the Southwest Oncology Group Online 
Specimen Tracking System.  Southwest Oncology Group members may 
log on to the Specimen Tracking System via the CRA Workbench 
(https://gill.crab/org/txwb/logon.aspx) using their Southwest Oncology 
Group roster identification numbers and passwords. First-time non-
Southwest Oncology Group users must refer to start-up instructions 
located at https://gill.crab.org/SpecTrack/. 
 
In the online Specimen Tracking System, laboratory ID numbers are 
used to identify the laboratories to which specimens are shipped.  The 
laboratory ID number for this study is: 
 
Lab # 107: 
U of Cincinnati/Path and Lab Correlates 
Contact: 
Chris Hackett/Dr. Fenoglio-Preiser 
Phone:  
513/558-4675 or 513/558-4500 
 
ALL SPECIMENS MUST BE LOGGED VIA THIS SYSTEM; THERE ARE 
NO EXCEPTIONS.  To report technical problems with Specimen 
Tracking, such as database errors or connectivity issues, please send an 
email to technicalquestion@crab.org.  For procedural help with logging 
and shipping specimens, there is an introduction to the system on the 
Specimen 
Tracking 
main 
page 
(http://dnet.crab.org/SpecTrack/Documents/SpecTPrimer-Insts.pdf); 
or 
contact the Data Operations Center at 206/667-2267 to be routed to the 
Data Coordinator for further assistance. 
 
A copy of the Shipment Packing List produced by the Specimen Tracking 
System should be printed and placed in the pocket of the specimen bag 
if it has one, or in a separate resealable bag. 
 
The bags should then be shipped in a standard Styrofoam shipping 
container which the sites can supply. PLEASE PACK TUBES 
CAREFULLY.  Cardboard express mail envelopes alone are NOT 
ADEQUATE—please additionally pack the tubes in Styrofoam or with 
extra padding.  If freezing conditions or extreme heat conditions are 
anticipated, insulated containers are recommended. 
 
All submitted specimens must be labeled with the protocol number 
(S9921), SWOG patient number, patient's initials, and date and time of 
specimen collection. 
 
All paraffin-embedded tissue samples should be mailed at ambient 
(room) temperature or placed on ice packs if shipped from warm 
climate areas. 
 
Blood, serum, and plasma should be shipped on dry ice by overnight 
carrier Monday through Wednesday only. 
 
Saturday, Sunday and Holiday Deliveries:  Specimens will NOT be 
accepted on Saturdays, Sundays, and holidays. 
 
2. 
The Federal guidelines for shipment are as follows: 
 
a. 
The specimen must be wrapped in an absorbable material. 
 
b. 
The specimen must be placed in an AIRTIGHT container (like a 
resealable bag). 
 


 
S9921 
 
Page 28d 
 
Amended 2/14/06 
 
 
 
 
c. 
Pack the resealable bag and specimen in a Styrofoam shipping 
container. 
 
d. 
Pack the Styrofoam shipping container in a cardboard box. 
 
e. 
The cardboard box must be marked as "BIOHAZARD". 
 
c. 
Blood Specimen Submission for Banking 
 
If the patient consents, please draw an additional blood sample at prestudy (after 
registration, but prior to receiving first dose of treatment), between Weeks 24 and 
28, and at progression for submission to the Southwest Oncology Group 
Repository per instructions above. 
 
Instructions for Processing of Blood Specimens 
 
1. 
Blood samples should be collected using standard venipuncture 
technique. 
 
2. 
A total of 20 mL of whole blood drawn in 3 separate tubes will be 
collected prior to treatment (at prestudy), between Weeks 24 and 28, 
and at progression.  Follow instructions in #3, 4 and 5 below. 
 
3. 
Serum:  10 ml of whole blood will be collected in red top vacutainer tubes 
(anticoagulant-free) and allowed to clot for approximately 30 minutes.  
Serum must be separated from cells within 45 - 60 minutes of veni-
puncture. 
 
a. 
Serum is separated from clotted blood by centrifugation at 3,000 
RPM for ten minutes.  Alternatively, serum can be separated by 
centrifugation at 3500 rpm for 30 minutes if the blood is being 
run with blood tubes for plasma samples (see below). 
 
b. 
Using a pipette, serum should then be equally aliquoted into 
three plastic storage/transport or cryotubes, and shipped 
according to the instructions below.  Avoid disturbing the cell or 
clot layer during the pipeting procedure.  Prolonged exposure to 
light, especially sunlight, should be avoided, but routine 
processing is not affected by normal, artificial laboratory lighting.  
Label cryovials with Patient ID#, cycle information and contents 
(e.g. plasma, serum, whole blood). 
 
4. 
Whole Blood:  Draw 5 mL of whole blood into an EDTA Lavender Top 
Tube, shake gently, and then separate sample equally into two (2) 
cryovials.  Sample may be stored at -20° to -70°C and shipped with 
aliquots from serum sample and plasma sample. 
 
5. 
Plasma:  Process sample within 30 minutes of blood draw.  Draw 5 ml of 
whole blood into an EDTA lavender top tube, invert gently, then 
centrifuge at 3500 rpm for 30 minutes.  Divide plasma into three cryovials 
in ~ 1.0 ml aliquots, and then freeze the samples immediately at -70°C. 
Samples MUST be shipped as soon as possible and sent by overnight 
courier, DO NOT ALLOW SAMPLES TO THAW.  If a -70°C freezer is not 
available plasma samples may be stored at -20°C until shipped.  Label 
cryovials with Patient ID#, cycle information and contents (e.g. plasma, 
serum, whole blood). 
 
NOTE:  If you need cryovials, please contact the Southwest Oncology Group 
Repository at 513/558-4675. 
 
 


Amended 2/14/06 
S9921 
Revised 4/3/06 
Page 28e 
 
Revised 2/1/07 
 
 
 
 
d. 
Tissue Submission for Banking 
 
With the patient's additional consent on the "Consent Form for Use of Specimens 
for Research," within 28 days of obtaining specimens, submit a biopsy specimen.  
Specimens of paraffin-embedded tissue should be shipped in appropriate mailing 
containers with adequate wrapping or cushioning to protect the specimens.  
These should be sent at ambient temperature, not on wet or dry ice (see 
instructions above). 
 
15.2 
CTSU Investigators - Special Materials or Substudies 
 
All specimens submitted for this study must be entered and tracked using the Southwest 
Oncology Group on-line Specimen Tracking System, as specified in protocol Section 
15.0.  You can also access the Tracking System from the CTSU Member Web Site.  Go 
to the S9921 protocol page and click on the link provided under the Case Report Forms 
header. 
 
Follow instructions as outlined in protocol Section 15.1. 
 
15.3 
CALGB Institutions 
 
The following should be submitted to: 
 
CALGB Pathology Coordinating Office 
The Ohio State University 
320 West 10th Avenue 
M364 Starling-Loving Hall 
Columbus, Ohio 43210 
Phone:  614/293-7073 
Fax:  614/293-7967 
 
a. 
Within one month of patient randomization submit: 
 
1. 
One formalin-fixed, paraffin-embedded block from a representative area 
of the primary tumor along with: 
 
i. 
Patient's name 
ii. 
CALGB patient number and Southwest Oncology Group patient 
number 
iii. 
CALGB study number and Southwest Oncology Group study 
number  
 
2. 
Original completed CALGB Form C-490 
 
3. 
A copy of the responsible pathologist's surgical pathology report from the 
TREATING institution, and, if applicable, the REFERRING institution. 
 
If the institution is unable to submit a tumor block, submit C-490 to the CALGB 
Pathology Coordinating Office (copy to the CALGB DMC) with letter from 
institutional pathologist stating reason why block will not be sent.  If patient does 
not consent to tissue submission, CALGB Form C-490 should be returned 
marked "Patient refused". 
 
These tissue blocks will be stored at 4°C and sectioned by the CALGB Pathology 
Reference Laboratory according to companion protocol guidelines for studies 
which are approved by the Intergroup GU Cancer Correlative Sciences 
Committee. 
 
b. 
At prestudy (after registration, but prior to receiving first dose of treatment), 
between Weeks 24 and 28, and at progression submit blood specimens as 
outlined in Section 15.1c. 
 


 
S9921 
 
Page 28f 
 
Amended 2/14/06 
 
 
 
 
16.0 
ETHICAL AND REGULATORY CONSIDERATIONS 
 
The following must be observed to comply with Food and Drug Administration regulations for the 
conduct and monitoring of clinical investigations; they also represent sound research practice: 
 
Informed Consent 
 
The principles of informed consent are described by Federal Regulatory Guidelines (Federal 
Register Vol. 46, No. 17, January 27, 1981, part 50) and the Office for Protection from Research 
Risks Reports:  Protection of Human Subjects (Code of Federal Regulations 45 CFR 46).  They 
must be followed to comply with FDA regulations for the conduct and monitoring of clinical 
investigations. 
 
Institutional Review 
 
This study must be approved by an appropriate institutional review committee as defined by 
Federal Regulatory Guidelines (Ref. Federal Register Vol. 46, No. 17, January 27, 1981, part 56) 
and the Office for Protection from Research Risks Reports:  Protection of Human Subjects (Code 
of Federal Regulations 45 CFR 46). 
 
 
Drug Accountability 
 
For each drug supplied for a study, an accountability ledger  containing current and accurate 
inventory records covering receipt, dispensing, and the return of study drug supplies must be 
maintained.  Drug supplies must be kept in a secure, limited access storage area under the 
recommended storage conditions.  During the course of the study, the following information must 
be noted on the accountability ledger; the identification code of the subject to whom drug is 
dispensed, the date(s) and quantity of drug dispensed to the subject, and the date(s) and quantity 
of drug returned by the subject; subjects should return empty containers to the investigator, with 
the return noted on the ledger.  These Accountability Forms must be readily available for 
inspection and are open to FDA or NCI inspection at any time. 
 
Monitoring 
 
This study will be monitored by the Clinical Data Update System (CDUS) version 1.1.  
Cumulative CDUS data will be submitted quarterly to CTEP by electronic means.  Reports are 
due January 31, April 30, July 31 and October 31. 
 
16.1 
Adverse Event Reporting Requirements  
 
a. 
Purpose 
 
Adverse event data collection and reporting, which are required as part of every 
clinical trial, are done to ensure the safety of patients enrolled in the studies as 
well as those who will enroll in future studies using similar agents. Adverse 
events are reported in a routine manner at scheduled times during a trial. 
(Directions for routine reporting are provided in Section 14.0.) Additionally, 
certain adverse events must be reported in an expedited manner to allow for 
more timely monitoring of patient safety and care. The following guidelines 
prescribe expedited adverse event reporting for this protocol.  See also Appendix 
19.5 for general and background information about expedited reporting. 
 
 


 
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Amended 2/14/06 
 
 
 
 
b. 
Reporting methods 
 
This study requires that expedited adverse event reporting use the NCI’s 
Adverse Event Expedited Reporting System (AdEERS). The NCI’s guidelines for 
AdEERS can be found at http://ctep.cancer.gov. An AdEERS report must be 
submitted to the Southwest Oncology Group Operations Office by one of the 
following methods: 
 
• 
Electronically submit the report via the AdEERS Web-based application 
located at http://ctep.cancer.gov, or 
 
• 
Only if submitting electronically is not possible, fax the completed 
NCI Adverse Event Expedited Report – Single Agent or Multiple Agents 
– paper template, located at http://ctep.cancer.gov, to 210/677-0006. 
Once Internet connectivity is restored, an AE report submitted on a 
paper template must be entered electronically into AdEERS by the 
original submitter at the site. 
 
c. 
When to report an event in an expedited manner 
 
When the adverse event requires expedited reporting, submit the report within 10 
calendar days of learning of the event. 
 
d. 
Other recipients of adverse event reports 
 
The Operations Office will forward reports and documentation to the appropriate 
regulatory agencies and drug companies as required. 
 
Adverse events determined to be reportable must also be reported according to 
local policy and procedures to the Institutional Review Board responsible for 
oversight of the patient. 
 
e. 
Expedited reporting for commercial agents 
 
Commercial reporting requirements are provided in Table 16.2. If there is any 
question about the reportability of an adverse event or if on-line AdEERS cannot 
be used, please telephone or email the SAE Program at the Operations Office, 
210/677-8808 or adr@swog.org, before preparing the report. 
 
Table 16.2. Expedited reporting requirements for adverse events 
experienced by patients who have received commercial drug(s) on this 
study.  
 
 
Grade 4 
 
Grade 5a 
Attribution 
Unexpected 
Expected 
Unexpected 
Expected 
Unrelated or Unlikely 
 
 
AdEERS 
AdEERS 
Possible, Probable,  
Definite 
AdEERS 
 
AdEERS 
AdEERS 
AdEERS:  Indicates an expedited report is to be submitted using the NCI AdEERS Commercial 
Drug pathway within 10 calendar days of learning of the event. 
 
a This includes all deaths within 30 days of the last dose of treatment with a commercial agent(s), 
regardless of attribution. Any death that occurs more than 30 days after the last dose of 
treatment with a commercial agent(s) and is attributed (possibly, probably, or definitely) to the 
agent(s) and is not due to cancer recurrence must be reported according to the instructions 
above. 
 
 


Amended 2/14/06 
S9921 
Revised 2/1/07 
Page 28h 
 
 
 
 
 
f. 
Reporting secondary AML/MDS/ALL 
 
All cases of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), 
and acute lymphocytic leukemia (ALL) that occur in patients on NCI-sponsored 
trials following chemotherapy for cancer must be reported using the NCI/CTEP 
Secondary AML/MDS Report Form in lieu of AdEERS. The following supporting 
documentation must also be submitted within 30 days: 
 
• 
a copy of the pathology report confirming the AML/MDS/ALL diagnosis; 
and 
• 
(if available) a copy of the cytogenetics report. 
 
Submit the Report and documentation to: 
 
 
Investigational Drug Branch 
and 
Southwest Oncology Group 
by fax at 301-230-0159 
ATTN: SAE Program 
 
14980 Omicron Drive 
 
San Antonio, Texas 78245-3217 
 
NOTE: If a patient has been enrolled in more than one NCI-sponsored study, the 
AML/MDS Report must be submitted for the most recent trial.  
 
Adverse Reaction Reporting Requirements for CALGB Institutions: 
 
CALGB participants should employ definitions of adverse events as described above.  Adverse 
reactions, both written and telephone reports, should be made directly to the Southwest 
Oncology Group and the NCI according to the institutions in those sections.  A copy of 
written AERs should also be sent to the CALGB Regulatory Affairs Coordinator: 
 
CALGB Central Office 
Attn:  Regulatory Affairs, Coordinator 
208 South LaSalle Street, Suite 2000 
Chicago, IL  60604-1104 
Fax:  312/345-0117 
 
Institutions are responsible for notifying their IRBs of toxicities reported as adverse events under 
these guidelines. 
 
Adverse Event (AE) Reporting for CTSU Investigators: 
 
1. 
CTSU sites must comply with the expectations of their local Institutional Review Board 
(IRB) regarding documentation and submission of adverse events.  Local IRBs must be 
informed of all reportable serious adverse reactions. 
 
2. 
CTSU sites will assess and report adverse events according to the guidelines and 
timelines specified in the protocol.  You may navigate to the CTEP Adverse Event 
Expedited Report System (AdEERS) from either the Adverse Events tab of the CTSU 
member homepage (https://members.ctsu.org) or by selecting Adverse Event Reporting 
Forms from the document center drop down list on the S9921 Web page. 
 
3. 
Do not send adverse event reports to the CTSU. 
 
4. 
Secondary AML/MDS/ALL reporting: Report occurrence of secondary AML, MDS, or ALL 
via the NCI/CTEP AML-MDS Report Form in lieu of AdEERS.  Submit the completed 
form and supporting documentation as outlined in the protocol. 
 
 


 
S9921 
 
Page 29 
 
 
 
 
17.0 
BIBLIOGRAPHY 
 
  1. 
Bagshaw MA, Cox RS, Hancock SL.  Control of prostate cancer with radiotherapy.  Long term 
results.  J Urol 152:1781-1785, 1994. 
 
  2. 
Zincke H, Utz DC.  Observation on surgical management of carcinoma of the prostate with limited 
nodal metastases.  Urology 24:107, 1984. 
 
  3. 
Hussain M.  Future directions in prostate cancer treatment: An oncologist’s perspective.  Prostate 
Supp 6:26-30, 1996. 
 
  4. 
Stein A, Dekernion JB, Smith RB, et al.  Prostate specific antigen levels after radical 
prostatectomy in patients with organ confined and locally extensive prostate cancer.  J Urol 
147:942-946, 1992.  
 
  5. 
Partin AW, Pound CR, Clemens JQ, et al.  Serum PSA after anatomic radical prostatectomy:  
The Johns Hopkins experience after 10 years.  Urol Clin N Amer 20(4):713-725, 1993. 
 
  6. 
Partin AW, Lee BR, Carmichael M, et al.  Radical prostatectomy for high-grade disease:  A re-
evaluation 1994.  J Urol 151:1583-1586, 1994. 
 
  7. 
Ohori M, Goad JR, Wheeler TM, et al.  Can radical prostatectomy alter the progression of poorly 
differentiated prostate cancer?.  J Urol 152:1843-1849, 1994. 
 
  8. 
Epstein JI, Pizov G, Walch PC.  Correlation of pathologic findings with progression after radical 
retropubic prostatectomy.  Cancer 71(11):3582-3593, 1993. 
 
  9. 
Fisher B, Fisher ER, Redmond C.  Ten-year results from the NSABP clinical trial evaluation the 
use of L-phenylalanine mustard (L-PAM) in the management of primary breast cancer.  JCO 
4:9290941, 1996. 
 
10. 
Moertel CG, Fleming TR, Macdonald JS, et al.  Levamisole and fluorouracil for adjuvant therapy 
of resected colon carcinoma.  NEJM 322:352-358, 1990. 
 
11. 
Ginsberg RJ, Vokes EE, Raben A.  Non-small cell lung cancer.  Section 30.2. In Principles and 
Practice of Oncology.  DeVita VT, Hellman S, Rosenberg SA, eds. 5th ed.  Philadelphia:  
Lippencott-Raven, 1997, pp. 858-911. 
 
12. 
Kirkwood JM, Strawderman MH, Ernstoff MS, et al.  Interferon alfa-2b adjuvant therapy of high 
risk resected cutaneous melanoma:  The Eastern Cooperative Oncology Group Trial EST 1684.  
JCO 14:7-17, 1998. 
 
13. 
Pilepich MV, Sause WT, Shipley WU, et al.  Androgen deprivation with radiation therapy 
compared with radiation therapy alone for locally advanced prostatic carcinoma:  a randomized 
comparative trial of the Radiation Therapy Oncology Group.  Urology 45:616-623, 1995. 
 
14. 
Porter AT, Elhilali M, Manji M, et al.  A Phase III randomized trial to evaluate the efficacy of 
neoadjuvant therapy prior to curative radiotherapy in locally advanced prostate cancer patients:  
A Canadian Urologic Oncology Group study.  Proc ASCO 16:315, #1123, 1997. 
 
15. 
Walsh PC, Partin AW, Epstein JI.  Cancer control and quality of life following anatomical radical 
retropubic prostatectomy for prostate cancer – results at 10 years.  J Urol 152:1831-1836, 1994. 
 
16. 
Catalona WJ, Smith DS.  Five-year tumor recurrence rates after anatomical radical retropubic 
prostatectomy for prostate cancer.  J Urol 152:1837-1842, 1994. 
 
17. 
Soloway MS, Sharifi R, Wajsman Z, McLeod D, Wood DP Jr., Puras-Baez A.  Randomized 
prospective study comparing radical prostatectomy alone versus radical prostatectomy preceded 


 
S9921 
 
Page 30 
 
 
 
by androgen blockade in clinical stage B2 (T2bNxM0) prostate cancer.  J Urol 154:424-428, 
1995. 
 
18. 
Witjes WP, Schulman CC, Debruyne FM.  Preliminary results of a prospective randomized study 
comparing radical prostatectomy versus radical prostatectomy associated with neoadjuvant 
hormonal combination therapy in T2-T3N0M0 prostatic carcinoma.  The European Study Group 
on Neoadjuvant Prostate Cancer.  Urology 49(3A Supplement):65-69, 1997. 
 
19. 
Fair WR, Cookson MS, Stroumbakis N, Cohen D, Aprikian AG, Want Y, Russo P, Soloway SM, 
Sogani P, Sheinfeld J, Herr H, Dalgabni G, Begg CB, Heston DW and Reuter VE.  The 
indications, rationale and result of neoadjuvant androgen deprivation in the treatment of prostatic 
cancer:  Memorial Sloan-Kettering Cancer Center results.  Urology 49(3A Supplement):46-55, 
1997. 
 
20. 
Labrie F, Dupont A, Cusan L, Gomez JL, Diamond P, Suburu R, Lemay M, Tetu B, Fradet Y, 
Belanger A, Candas B.  Neoadjuvant hormonal therapy: The Canadian experience.  Urology  
49(3A Supplement):56-64, 1997. 
 
21. 
Goldberg SL, Klotz LH, Sprigley J, Jewett MAS, Mador D, Fradet Y, Barkin J, Chin J, Paquin JM, 
Bullock MJ, Laplante S and Canadian urologic oncology group.  Randomized, prospective 
controlled study comparing radical prostatectomy alone and neoadjuvant androgen withdrawal in 
the treatment of localized prostate cancer.  J Urol 156:873-877, 1996. 
 
22. 
Soloway MS, Sharifi R, Wajsman Z, McLeod D, Wood DP, Jr.  Radical prostatectomy alone vs. 
radical prostatectomy preceded by androgen blockade in cT2b prostate cancer. J Urol 157:160, 
1997 (Abstract). 
 
23. 
Harris J, Morrow M, Norton L.  Malignant tumors of the breast. . In Principles and Practice of 
Oncology.  DeVita VT, Hellman S, Rosenberg SA, eds. 5th ed.  Philadelphia:  Lippencott-Raven, 
1997, pp. 1557-1616. 
 
24. 
Murphy WM, Soloway MS, Barrows GH.  Pathologic changes associated with androgen 
deprivation therapy for prostate cancer. Cancer 68:821-828, 1991. 
 
25. 
Zagars GK, Johnson DE, Von Eschenbach AC, et al.  Adjuvant estrogen following radiation 
therapy for stage C adenocarcinoma of the prostate: long-term results of a prospective 
randomized study.  Int J Rad Onc Biol Phys 14:1085-1091, 1988. 
 
26. 
Schmidt JD, Gibbons RP, Murphy GP, Bartolucci A.  Adjuvant estramustine phosphate treatment 
for localized prostate cancer.  PPO updates 11(10):1-9, 1997. 
 
27. 
Pilepich MV, Caplan R, Byhardt RW et al.  Phase III trial of androgen suppression using goserelin 
in unfavorable prognosis carcinoma of the prostate treated with definitive radiotherapy:  report of 
Radiation Therapy Oncology Group protocol 85-31.  J Clin Oncol 15:1013-1021, 1997. 
 
28. 
Bolla M, Gonzalez D, Warde P, et al.  Improved survival in patients with locally advanced 
prostate cancer treated with radiotherapy and goserelin.  NEJM 337:295-300, 1997. 
 
29. 
Pienta KJ, Redman B, Hussain M, et al.  Phase II evaluation of oral estramustine and oral 
etoposide in hormone refractory adenocarcinoma of the prostate.  J Clin Onc 12:2005-2012, 
1994. 
 
30. 
Hudes GR, Nathan F, Khater C, et al.  Phase II trial of 96-hour paclitaxel plus oral estramustine 
phosphate in metastatic hormone-refractory prostatic cancer.  JCO 15:3156-3163, 1997. 
 
31. 
Tannock IF, Osoba D, Stockler M, et al.  Chemotherapy with mitoxantrone plus prednisone or 
prednisone alone for symptomatic hormone resistant prostate cancer.  A Canadian randomized 
trial with palliative endpoints.  J Clin Onc 14:1756-1764, 1996.  
 
32. 
Kantoff PW, Conoway M, Winer E, et al.  Hydrocortisone with or without mitoxantrone in patients 
with hormone refractory prostate cancer; Preliminary results from a prospective randomized 


 
S9921 
 
Page 31 
 
 
 
Cancer and Leukemia Group B study (9182) comparing chemotherapy to best supportive care.  
Proc Am Soc Clin Onc 15:25 (addendum), abstr #2013, 1996. 
 
33. 
Gibbons RP, Cole BS, Richardson RG, Correea RJ Jr., Brannen GE, Mason JT, Taylor WJ, 
Hafermann MD.  Adjuvant radiotherapy following prostatectomy:  results and complications.  J 
Urol 135(1):65-68, 1986. 
 
34. 
Anscher MS, Prosnitz LR.  Postoperative radiotherapy for patients with carcinoma of the prostate 
undergoing radical prostatectomy with positive surgical margins, seminal vesicle involvement 
and/or penetration through the capsule.  J Urol 138(6):1407-1412, 1987. 
 
35. 
Eusbrycg A, Perez CA, Roessler EH, Lockett MA.  Adjuvant irradiation after prostatectomy for 
caricnoma of the prostate with positive surgical margins.  Cancer 73(2):384-388, 1994. 
 
36. 
Paulson DF, Moul JW, Robertson JE, Walther PJ.  Postoperative radiotherapy of the prostate for 
patients undergoing radical prostatectomy with positive margins, seminal vesicle involvement 
and/or penetration through the capsule.  J Urol 143(6):1178-1182, 1990. 
 
37. 
Walsh PC.  Adjuvant radiotherapy after radical prostatectomy:  is it indicated?  J Urol 
138(6):1427-1428, 1987. 
 
38. 
Ray GR, Bagshaw MA, Freiha F.  External beam radiation salvage for residual or recurrent local 
tumor following radical prostatectomy.  J Urol 132(5):926-930, 1984. 
 
39. 
Morris MM, Dallow KC, Zietman AL, Park J, Althausen A, Heney NM, Shipley WU.  Adjuvant and 
salvage irradiation following radical prostatectomy for prostate cancer.  Int J radiat Oncol Biol 
Phys 38(4):731-736, 1997. 
 
40. 
Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD, Walsh PC.  Natural History of 
Progression After PSA Elevation Following Radical Prostatectomy.  JAMA 281(17):1591-1597, 
1999. 
 


 
S9921 
 
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Revised 7/1/02 
 
Revised 8/1/02 
 
Amended 2/14/06 
 
 
 
 
 
18.0 
MASTER FORMS SET 
 
This section includes copies of all data forms which must be completed for this study.  These 
include: 
 
18.1 
Model Consent Form (to be reviewed and approved by the Institutional Review Board 
prior to patient registration on the study). 
 
18.2 
Southwest Oncology Group Registration Form (Form #26636) (3/15/06) and Guidelines 
 
18.3 
S9921 Local Prostate Carcinoma Prestudy (Form #23968) (3/15/06) 
 
18.4 
S9921 PSA Reporting Form (Form #59255) (3/15/06) 
 
18.5 
S9921 Testosterone Reporting Form (Form #25939) (3/15/06) 
 
18.6 
S9921 Treatment Form (Form #38859) (3/15/06) 
 
18.7 
S9921 Chemotherapy Treatment Form (Form #61544) (3/15/06) 
 
18.8 
S9921 Adverse Event Summary Form (Form #27242) (3/15/06) 
 
18.9 
Follow-Up Form (Form #64587) (9/15/03) 
 
18.10 
Off Treatment Notice (Form #8756) (9/1/03) 
 
18.11 
Notice of Death (Form #49467) (9/1/03) 
 


 
S9921 
 
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Revised 6/1/00 
 
Revised 7/1/01 
 
 
 
 
 
This model informed consent form has been reviewed by the DCT/NCI and is the official consent 
document for this study. Local IRB changes to this document are allowed.  (Institutions should attempt to 
use sections of this document which are in bold type in their entirety.)  Editorial changes to these sections 
may be made as long as they do not change information or intent.  If the institutional IRB insists on 
making deletions or more substantive modifications to the risks or alternatives sections, they may be 
justified in writing by the investigator and approved by the IRB.  Under these circumstances, the revised 
language, justification and a copy of the IRB minutes must be forwarded to the Southwest Oncology 
Group Operations Office for approval before a patient may be registered to this study. 
 
Readability Statistics:   Flesch Reading Ease 
 
61.3 (targeted above 55) 
 
 
 
Flesch-Kincaid Grade Level 
8.2 (targeted below 8.5) 
 
 
S9921, "Adjuvant Androgen Deprivation versus Mitoxantrone Plus 
Prednisone Plus Androgen Deprivation in Selected High Risk Prostate 
Cancer Patients Following Radical Prostatectomy" 
 
PHASE III 
 
This is a clinical trial (a type of research study). Clinical trials include only patients who choose 
to take part. Please take your time to make your decision. Discuss it with your family and 
friends. 
 
You are being asked to take part in this study because you have prostate cancer considered to be 
high risk, and your prostate has been removed by surgery. 
 
It is suggested that CTSU institutions incorporate the following paragraph in their consent form: 
(7/1/01) 
 
You have been asked to participate in a research study because you have [INSERT BRIEF 
DESCRIPTION OF DISEASE BEING STUDIED]. This study is being performed by the 
doctors at [INSERT INSTITUTION NAME] who are members of the National Network of 
participating physicians and sponsored by the National Cancer Institute's Cancer Trial Support 
Unit. (paragraph added 6/1/00) 
 
 
Why Is This Study Being Done? 
 
The purpose of this study is to compare the effects (good and bad) of the 
addition of chemotherapy (mitoxantone and prednisone) to a standard 
hormone therapy with hormone therapy given alone on you and your 
prostate cancer to see which is better.  
 
 


 
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Amended 2/14/06 
 
 
 
(2/14/06) 
 
How Many People Will Take Part in the Study 
 
Nationally, about 1,360 people will take part in this study. 
 
(paragraphs deleted 2/14/06) 
 
 
What Is Involved in the Study? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
You will be "randomized" into one of the study groups described above. 
Randomization means that you are put into a group by chance. It is like flipping a 
coin. Which group you are put in is done by a computer. Neither you nor the 
researcher will choose what group you will be in. You will have an equal chance 
of being placed in any group. 
 
 
Randomization 
 
 
 
 
Casodex + Zoladex 
Casodex + Zoladex 
(Arm 1) 
plus Mitoxantrone 
 
and Prednisone. 
 
(Arm 2) 
 
 
 
 
Follow for Survival or 
 
for a maximum of 15 years 


 
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Amended 2/14/06 
 
 
 
 
If you take part in this study you will be randomized to either Arm 1 or Arm 2 as 
described in the chart above.  Depending on which arm you are placed in you will 
receive treatment as described in the following sections: 
 
ARM 1 (Hormonal Therapy) 
 
Medical Tests: 
 
The following tests may be done to make sure that you are eligible for this study.  
None of these tests are experimental.  They are routine.  You may not need to 
have all of these tests done.  Depending on when you last had them, you may 
need to repeat some of these tests: 
 
• Blood Tests 
 
• Bone Scan 
 
• CAT scan of your abdomen/lower abdomen 
 
• Electrocardiogram 
 
• A special x-ray to study the heart (MUGA scan) 
 
Many of the tests will also be repeated during the study.  If you participate in this 
study, some of these tests may be done more frequently than if you were not 
taking part in this research study. 
 
Procedures (treatment): 
 
If you are eligible and agree to take part in this study you will receive: 
 
• Goserelin Acetate (Zoladex®) as an injection every 3 months for two years.  
(2/14/06) 
 
• Bicalutamide (Casodex®) is taken once a day for two years. 
 
• 
ARM 2 (Hormonal Therapy Plus Mitoxantrone Plus Prednisone) 
 
Medical Tests: 
 
The following tests may be done to make sure that you are eligible for this study.  
None of these tests are experimental.  They are routine.  You may not have to 
have all of these tests done.  Depending on when you last had them, you may 
need to repeat some of these tests: 
 
• 
Blood Tests 
 


 
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Amended 2/14/06 
 
 
 
 
• 
Bone Scan 
 
• 
CAT scan of your abdomen/lower abdomen 
 
• 
Electrocardiogram 
 
• 
A special x-ray to study the heart (MUGA scan) 
 
Many of the tests will also be repeated during the study.  If you participate in this 
study, some of these tests may be done more frequently than if you were not 
taking part in this research study. 
 
Procedures (treatment): 
 
If you are eligible and agree to take part in this study you will receive: 
 
• 
Goserelin Acetate (Zoladex®) as an injection every 3 months for two years.  
(2/14/06)  
 
• 
Bicalutamide (Casodex®) every day for two years.  Bicalutamide is taken once 
a day for two years. 
 
• Mitoxantrone and prednisone 6 times.  Mitoxantrone is given through a needle 
in a vein on the first day of each 21 day cycle.  Prednisone is given twice per 
day by mouth every day until the 6 cycles are finished.  Each dose regimen 
will be 21 days apart. 
 
 
How Long Will I Be in the Study? 
 
Your hormonal therapy will last 2 years.  We would like to keep track of your 
medical condition for fifteen years to look at the long-term effects of the study. 
 
The researcher may decide to take you off this study if your disease gets worse 
despite the treatment; the side effects of the treatment are too dangerous for you; 
new information about the treatment becomes available and this information 
suggests the treatment will be ineffective or unsafe for you.  
 
What Are the Risks of the Study? 
 
While on the study, you are at risk for these side effects. You should discuss 
these with the researcher and/or your regular doctor. There also may be 
other side effects that we cannot predict. Other drugs will be given to make 
side effects less serious and uncomfortable. Many side effects go away shortly 
after the drugs are stopped, but in some cases side effects can be serious or 
long-lasting or permanent.  
 


 
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Amended 2/14/06 
 
 
 
 
Side effects of Hormonal Therapy with Goserelin Acetate (Zoladex®) and 
Bicalutamide (Casodex®): 
 
ARM 1: (text bolded 2/14/06)  
 
Very likely:    
 
• 
Hot flashes 
 
• 
Nausea 
 
• 
Dizziness 
 
• 
Diarrhea 
 
• 
Constipation 
 
• 
Fatigue 
 
• 
Pain (back, abdominal, pelvic or in general) 
 
• 
Swelling of hands or feet 
 
• 
Impotence 
 
• Loss of bone mineral density  (2/14/06) 
 
Less likely: 
 
• 
Breast tenderness and swelling 
 
• 
Mild skin rash 
 
• 
Decreased testicular size 
 
• 
Weakness  (items added 2/14/06) 
 
• 
Anemia   
 
• 
Increased liver enzymes (blood tests)   
 
• 
Weight gain   
 
• 
Osteoarthritis   
 


 
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Amended 2/14/06 
 
 
 
 
Side effects of Hormonal Therapy plus Mitoxantrone plus Prednisone: 
 
ARM 2: (text bolded 2/14/06) 
 
Very likely:   
 
• 
Lowered white blood count may lead to an infection 
 
• 
Lowered platelets may lead to an increase in bruising or bleeding 
 
• 
Nausea, vomiting, or diarrhea 
 
• 
Constipation 
 
• 
Fatigue 
 
• 
Temporary complete hair loss 
 
• 
Loss of appetite 
 
• 
High or low blood pressure 
 
• 
Numbness or tingling in fingers or toes 
 
• 
Pain in muscles and joints 
 
• 
Muscle weakness 
 
• 
Swelling of the feet, abdomen, or face (fluid retention) 
 
• 
Impotence 
 
• 
Urine color changes (blue-green) 
 
• 
Dizziness/lightheadedness 
 
• 
Rash 
 
• 
Hot flashes 
 
• 
Pain (back, abdominal, pelvic or in general) 
 


 
S9921 
 
Page 38a 
 
Amended 2/14/06 
 
 
 
Less likely:   (text bolded 2/14/06) 
 
• 
Breast tenderness and swelling 
 
• 
Allergic reactions (may happen during injection) 
 
• 
Irregular heartbeat 
 
• 
Weakening of heart muscle 
 
• 
Whites of eyes slightly bluish 
 
• 
Lowered red blood cells may lead to anemia, tiredness, or shortness of 
breath 
 
• 
Decreased testicular size 
 
• Mild skin rash 
 
• Infection (items from here on added 2/14/06) 
 
• Weight gain 
 
• Weight loss 
 
• Fever without infection 
 
• Shortness of breath 
 
• Nail bed changes 
 
• Mouth or lip sores 
 
• Sweats 
 
• Mood changes (anxiety, depression, irritability) 
 
• Cough 
 
• Heartburn 
 


 
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Amended 2/14/06 
 
 
 
Rare, but Serious:  (added 2/14/06) 
 
Mitoxantrone has been reported to cause leukemia. 
 
(paragraph deleted 2/14/06) 
 
 
Are There Benefits to Taking Part in the Study? 
 
We cannot and do not guarantee you will benefit if you take part in this 
study.  The treatment you receive may even be harmful.  Your doctors feel 
that your participation in this study will give you at least as good a chance as 
you might expect from other treatments.  We hope the information learned 
from this study will benefit other patients with prostate cancer in the future. 
 
(paragraph deleted 2/14/06) 
 
 
What Other Options Are There? 
 
Instead of being in this study, you have these options: 
Other types of chemotherapy, radiation or no anti-cancer treatment at this 
time (with care to help you feel more comfortable). 
 
You can get treatment for prostate cancer without being on this study.  All of 
the treatment on this study may be available at this center or at other 
locations. 
 
Please talk to your regular doctor about these and other options. 
 
 
What about Confidentiality? 
 
Efforts will be made to keep your personal information confidential. We cannot 
guarantee absolute confidentiality. Your personal information may be disclosed if 
required by law.  
 


Revised 4/15/00 
Revised 6/1/00 
S9921 
Revised 5/15/00 
Amended 2/14/06 
Page 40 
 
 
 
 
 
Organizations that may inspect and/or copy your research records for quality 
assurance and data analysis include groups such as:  the National Cancer Institute, 
a qualified representative of the drug manufacturers, the Food and Drug 
Administration, CALGB and the Southwest Oncology Group.  (5/15/00) 
 
If we publish the information we learn from this study in a medical journal, you 
will not be identified by name or in any other way. 
 
FOR CTSU INVESTIGATORS ONLY 
 
While you are participating in this study a record of your progress on this study 
will be kept in a confidential form at [INSERT NAME OF INSTITUTION] and 
sent to the sponsor who will add this information to a computer file. The 
confidentiality of any central computer record will be carefully guarded and no 
information by which you can be identified will be released or published.  You 
have been informed that authorized representatives of [INSERT GROUP NAME 
and the CLINICAL TRIALS SUPPORT UNIT], the National Cancer Institute, 
The Food and Drug Administration (FDA), and [INSERT NAME OF 
INSTITUTION AND INSTITUTIONAL REVIEW BOARD HERE] may 
inspect and copy the records. ([Optional, if applicable] An authorized 
representative of the manufacturers of the drugs used in this study may also 
have access to your study records.)  Your identity will remain confidential and 
your records will be used by these authorized representatives only in connection 
with carrying out their obligations relating to the clinical trial and they shall not 
be used for any other purpose or disclosed to any third party except with your 
express permission. (Paragraph added 6/1/00) 
 
What Are the Costs? 
 
Taking part in this study may lead to added costs to you or your insurance 
company. Please ask about any expected added costs or insurance problems. 
 
In the case of injury or illness resulting from this study, emergency medical 
treatment is available but will be provided at the usual charge. No funds have 
been set aside to compensate you in the event of injury.  (local institutions must 
choose the option that best fits the hospital's situation) 
 
You or your insurance company will be charged for continuing medical care 
and/or hospitalization. 
 
You will receive no payment for taking part in this study. 
 
Administration of the drug will be (provided free of charge/charged in the usual 
way).  The goserelin acetate (Zoladex®) and the bicalutamide (Casodex®) will be 
provided free of charge for this study by the manufacturer (Astra Zeneca).  (4/15/00)  
The mitoxantrone will be provided free of charge for this study by OSI 
Pharmaceuticals.  (4/15/00, 2/14/06)  The prednisone is commercially available and 
will be charged in the usual way.  The parts of the research consisting of keeping 
research records will be paid by those organizing and conducting the research.  The 
research requires that you receive certain standard medical tests and examinations.  


 
S9921 
 
Page 40a 
 
Revised 6/1/00 
 
 
 
 
 
(Repagination page 6/01/00) 
 
These standard tests and examinations will be (charged in the usual way/provided 
at a reduced rate).  (local institutions must choose the option that best fits the 
hospital's situation) 
 
 
What Are My Rights as a Participant? 
 
Taking part in this study is voluntary. You may choose not to take part or may 
leave the study at any time. Leaving the study will not result in any penalty or 
loss of benefits to which you are entitled. You can stop participating at any time. 
However, if you decide to stop participating in the study, we encourage you to 
talk to the researcher and your regular doctor first. 
 
A Data Safety and Monitoring Board, an independent group of experts, will be 
reviewing the data from this research throughout the study. We will tell you about 
important new information from this or other studies that may affect your health, 
welfare, or willingness to stay in this study. 
 


 
S9921 
 
Page 41 
 
Amended 2/14/06 
 
 
 
 
Whom Do I Call if I Have Questions or Problems? 
 
For questions about the study or a research-related injury, contact the researcher     
name(s) _______ at _______ telephone number __________. 
 
For questions about your rights as a research participant, contact the     name of 
center     Institutional Review Board (which is a group of people who review the 
research to protect your rights) at _________ telephone number _____. [And, if 
available, list patient representative (or other individual who is not on the research 
team or IRB)]. 
 
(section added 2/14/06) 
 
Please note:  This section of the informed consent form is about additional 
research studies that are being done with people who are taking part in the 
main study.   You may take part in these additional studies if you want to.  
You can still be a part of the main study even if you say 'no' to taking part in 
any of these additional studies. 
 
You can say "yes" or "no" to each of the following studies.  Please mark 
your choice for each study. 
 
[The following example of tissue consent has been taken from the NCI Cancer Diagnosis 
Program’s model tissue consent form found at the following url 
http://www.cancerdiagnosis.nci.nih.gov/specimens/model.pdf] 
 
Consent Form for Use of Specimens for Research (2/14/06) 
 
About Using Specimens for Research  
You have had a prostatectomy (surgery to remove the prostate). Your doctor has removed some 
body tissue to do some tests. The results of these tests will be given to you by your doctor and 
will be used to plan your care.  If you agree, you will have about 2 tablespoons of blood drawn 
before your first treatment, again between Weeks 24 and 28 of treatment, and when you go off 
protocol treatment.  
 
We would like to keep some of the tissue and blood for future research. If you agree, these 
specimens will be kept and may be used in research to learn more about cancer and other diseases. 
Please read the information sheet called "How are Specimens Used for Research" to learn more 
about specimen research.   
 


 
S9921 
 
Page 41a 
 
Amended 2/14/06 
 
 
 
 
Your specimens will be kept at: 
 
Cecilia M. Fenoglio-Preiser, M.D. 
University of Cincinnati 
231 Albert Sabin Way 
PO Box 670529 
Cincinnati, OH 45267-0529 
Phone:  513/558-4500 
FAX:  513/558-2289 
E-mail:  cecilia.fenogliopreiser@uc.edu 
 
The research that may be done with your specimens is not designed specifically to help you. It 
might help people who have cancer and other diseases in the future.  
Reports about research done with your specimens will not be given to you or your doctor. 
These reports will not be put in your health record. The research will not have an effect 
on your care.  
Things to Think About  
The choice to let us keep the left over specimens for future research is up to you. No 
matter what you decide to do, it will not affect your care.  
If you decide now that your specimens can be kept for research, you can change your 
mind at any time. Just contact us and let us know that you do not want us to use your 
specimens. Then any specimens that remain will no longer be used for research.  
In the future, people who do research may need to know more about your health. While 
the Southwest Oncology Group may give them reports about your health, it will not give 
them your name, address, phone number, or any other information that will let the 
researchers know who you are.  
Sometimes specimens are used for genetic research (about diseases that are passed on in 
families). Even if your specimens are used for this kind of research, the results will not 
be put in your health records.  
Your specimens will be used only for research and will not be sold. The research done 
with your specimens may help to develop new products in the future.  
Benefits 
The benefits of research using specimens include learning more about what causes cancer 
and other diseases, how to prevent them, and how to treat them.  
Risks 
The greatest risk to you is the release of information from your health records. We will do our 
best to make sure that your personal information will be kept private.  The chance that this 
information will be given to someone else is very small.  


 
S9921 
 
Page 41b 
 
Amended 2/14/06 
 
 
 
 
Making Your Choice 
Please read each sentence below and think about your choice. After reading each 
sentence, circle "Yes" or "No."  If you have any questions, please talk to your doctor or 
nurse, or call our research review board at IRB's phone number.  
No matter what you decide to do, it will not affect your care. 
1.  
My specimens may be kept for use in research to learn about, prevent, treat 
or cure cancer.    
Yes 
No 
2.  
My specimens may be kept for use in research about other health problems 
(for example: diabetes, Alzheimer's disease, or heart disease).   
Yes 
No 
3.  
Someone may contact me in the future to ask me to allow other uses of my 
specimens.   
Yes 
No 
If you decide to withdraw your specimens from a Southwest Oncology Group 
Specimen Repository in the future, a written withdrawal of consent should be 
submitted through your treating physician to the Southwest Oncology Group 
Operations Office.  Please designate in the written withdrawal whether you would 
prefer to have the specimens destroyed or returned to the treating physician. 
 
 
Where Can I Get More Information? 
 
[To IRB/Investigators:  Attach information materials and checklist of 
attachments. Signature page should be at the end of package.  You may also wish 
to include the following informational resources]. 
 
You may call the NCI’s Cancer Information Service at 
1–800–4–CANCER (1–800–422–6237) or TTY: 1–800–332–8615 
 
Visit the NCI's Web sites… 
Cancer Trials: comprehensive clinical trials information 
http://cancertrials.nci.nih.gov. 
 
CancerNet™: accurate cancer information including PDQ 
http://cancernet.nci.nih.gov. 
 
You will get a copy of this form. You may also request a copy of the protocol 
(full study plan). 
 


 
S9921 
 
Page 42 
 
Revised 7/1/01 
 
Amended 2/14/06 
 
 
 
 
SIGNATURE 
You are deciding whether or not to take part in this study.  If you sign, it means 
that you have decided to volunteer to take part in this study, and that you have 
read and understood all the information on this form. 
 
 
Participant  
 
Date ___________________ 
 
(section deleted 2/14/06) 


 
S9921 
 
Page 43 
 
Amended 2/14/06 
 
 
 
 
Specimen Consent Supplemental Sheets (added 2/14/06) 
 
How are Specimens Used for Research? 
 
Where do specimens come from? 
 
A specimen may be from a blood sample or from bone marrow, skin, toenails or other body materials.  
People who are trained to handle specimens and protect donors' rights make sure that the highest 
standards of quality control are followed by the Southwest Oncology Group.  Your doctor does not work 
for the Southwest Oncology Group, but has agreed to help collect specimens from many patients.  Many 
doctors across the country are helping in the same way.   
 
Why do people do research with specimens? 
 
Research with specimens can help to find out more about what causes cancer, how to prevent it, how to 
treat it, and how to cure it.  Research using specimens can also answer other health questions.  Some of 
these include finding the causes of diabetes and heart disease, or finding genetic links to Alzheimer's. 
 
What type of research will be done with my specimen? 
 
Many different kinds of studies use specimens.  Some researchers may develop new tests to find 
diseases.  Others may develop new ways to treat or even cure diseases.  In the future, some of the 
research may help to develop new products, such as tests and drugs.  Some research looks at diseases 
that are passed on in families (called genetic research).  Research done with your specimen may look for 
genetic causes and signs of disease. 
 
How do researchers get the specimen? 
 
Researchers from universities, hospitals, and other health organizations conduct research using 
specimens.  They contact the Southwest Oncology Group and request samples for their studies.  The 
Southwest Oncology Group reviews the way that these studies will be done, and decides if any of the 
samples can be used. The Southwest Oncology Group gets the specimen and information about you 
from your hospital, and sends the specimen samples and some information about you to the researcher.  
The Southwest Oncology Group will not send your name, address, phone number, social security number 
or any other identifying information to the researcher. 
 
Will I find out the results of the research using my specimen? 
 
You will not receive the results of research done with your specimen.  This is because research can take 
a long time and must use specimen samples from many people before results are known.  Results from 
research using your specimen may not be ready for many years and will not affect your care right now, 
but they may be helpful to people like you in the future. 
 
Why do you need information from my health records? 
 
In order to do research with your specimen, researchers may need to know some things about you.  (For 
example:  Are you male or female?  What is your race or ethnic group? How old are you?  Have you ever 
smoked?)  This helps researchers answer questions about diseases.  The information that will be given 
to the researcher may include your age, sex, race, diagnosis, treatments and family history.  This 
information is collected by your hospital from your health record and sent to the Southwest Oncology 
Group.  If more information is needed, the Southwest Oncology Group will send it to the researcher. 
 
Will my name be attached to the records that are given to the researcher? 
 
No.  Your name, address, phone number and anything else that could identify you will be removed before 
they go the researcher.  The researcher will not know who you are. 
 


 
S9921 
 
Page 44 
 
Amended 2/14/06 
 
 
 
 
How could the records be used in ways that might be harmful to me? 
 
Sometimes, health records have been used against patients and their families.  For example, insurance 
companies may deny a patient insurance or employers may not hire someone with a certain illness (such 
as AIDS or cancer).  The results of genetic research may not apply only to you, but to your family 
members too.  For disease caused by gene changes, the information in one person's health record could 
be used against family members. 
 
How am I protected? 
 
The Southwest Oncology Group is in charge of making sure that information about you is kept private.  
The Southwest Oncology Group will take careful steps to prevent misuse of records.  Your name, 
address, phone number and any other identifying information will be taken off anything associated with 
your specimen before it is given to the researcher.  This would make it very difficult for any research 
results to be linked to you or your family.  Also, people outside the research process will not have access 
to results about any one person which will help to protect your privacy. 
 
What if I have more questions? 
 
If you have any questions, please talk to your doctor or nurse, or call our research review board at (Insert 
IRB's Phone Number). 
 
 
 


Southwest Oncology Group Operations Office
14980 Omicron Drive
San Antonio, TX  78245-3217
Phone: (210) 677-8808
Fax: (210) 677-0006
Southwest  Oncology  Group  Registration Form
3/15/2006
Adjuvant Androgen Deprivation Versus Mitoxantrone
Plus Prednisone Plus Androgen Deprivation in
Selected High Risk Prostate Cancer Patients
Following Radical Prostatectomy, Phase III
Pathologic stage of disease:
Organ confined
Not organ confined, but N0
N1
Stratification Factors:
Performance Status:
cm
Height:
Weight:
.
kg
BSA:
.
m2
Gleason's Sum:
<7
7
>7
RT intended:
Yes
No
SWOG Study No.
S 9 9 2 1
Registration Step
1
Assigned Treatment Arm
Activation Date: October 15, 1999
Last Amended Date: March 15, 2006
Patient's Name
SWOG Patient ID
Other Group Patient ID
Other Group Name/
Protocol Number
INSTRUCTIONS: All of the information on this Registration Form and the Protocol Eligibility Section must be answered appropriately for
a patient to be considered eligible for registration.  This Registration Form must be entirely filled out and referred to during the
registration.  Do NOT submit this form as part of the patient data.
Caller's SWOG Roster ID
SWOG Investigator Number
SWOG Treating Institution Number
OR
OR
IRB Approval Date
/
/
Other Group Investigator Name and Number
Other Group Treating Institution Name and Number
Date Informed Consent Signed
/
/
/
/
If a resident of Canada:
Postal Code:
-
Social Insurance Number:
-
-
Country of Residence, if not USA:
Patient's Social Security Number:
-
-
If a U.S. resident:
Black or African American
White or Caucasian
Native Hawaiian or Other Pacific Islander
Asian
American Indian or Alaska Native
Unknown
Patient's Race (select all that apply):
Patient's Sex:
Female
Male
Patient's Date of Birth:
/
/
Method of Payment:
Patient's Ethnicity:
Please indicate how the patient answered the following questions on the consent form:
1. My specimens may be kept for
use in research to learn about,
prevent, treat or cure cancer.
Yes
No
2. My specimens may be kept for use in
research about other health problems
(for example: diabetes, Alzheimer's
disease, or heart disease).
Yes
No
3.  Someone may contact me in the
future to ask me to allow other uses
of my specimens.
Yes
No
Southwest Oncology Group Data Operations Center
C/o Cancer Research And Biostatistics
1730 Minor Ave, Suite 1900
Seattle, WA 98101-1468
Patient Registration:
via WebReg at: http://swog.org
    (24 hours a day, 7 days a week, excluding downtimes for maintenance)
or call 206-652-2267 (Mon-Fri, 6:30am-4:00pm Pacific Time, excluding holidays)
26636


 
 
 
 
Southwest Oncology Group Registration Form Code Sheet  
12/8/2004  
 
 
Race code definitions: 
 
White or Caucasian:  a person having origins in any of the original peoples of Europe, Middle 
East, or North Africa 
 
Black or African American:  a person having origins in any of the black racial groups of 
Africa. 
 
Native Hawaiian or Other Pacific Islander:  a person having origins in any of the original 
peoples of Hawaii, Guam, Samoa and other Pacific islands. 
 
Asian:   a person having origins in any of the original peoples of the Far East, Southeast Asia, 
or the Indian subcontinent.  Including, for example, Cambodia, China, India, Japan, Korea, 
Malaysia, Pakistan, the Philippine Islands, Thailand and Vietnam. 
 
American Indian or Alaska Native:  a person having origins in any of the original peoples of 
North, Central or South America, and who maintains tribal affiliations or community 
attachment. 
 
 
Ethnicity (Spanish/Hispanic Origin) codes: 
0 - Unknown  
1 - No (not Spanish)  
2 - Yes, Mexican  
3 - Yes, Puerto Rican 
4 - Yes, Cuban  
5 - Yes, Central American  
6 - Yes, South American 
7 - Yes, Other  
8 - Yes, NOS 
 
 
Method of Payment codes: 
01 - Private  
02 - Medicare  
03 - Medicare and Private  
04 - Medicaid 
05 - Medicaid and Medicare  
07 - No insurance (self-pay) 
08 - No insurance (no means)  
09 - Other, specify at registration 
10 - Unknown  
11 - Veterans Admin  
12 - Military 
 
 
Other Group codes for use in the Web Registration program:
9977 - ACOSOG 
9982 - CALGB  
9976 - CTSU 
9995 - ECOG 
9979 - EPP  
9984 - GOG  
9996 - NCCTG  
9981 - NCIC  
9983 - NSABP 
9997 - RTOG
 


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SOUTHWEST ONCOLOGY GROUP
S9921 LOCAL PROSTATE CARCINOMA PRESTUDY
3/15/2006
(L, F M)
Page 2 of 3
Histologic Grade:
Grade cannot be assessed, GX
Well differentiated (slight anaplasia), G1
Moderately differentiated (moderate anaplasia), G2
Poorly differentiated, G3
Undifferentiated (marked anaplasia), G4
DISEASE DESCRIPTION, continued
SWOG Study No. S 9 9 2 1
Registration Step 1
continued on next page
Gleason's Score:
Based on surgical specimen
Primary:
Secondary:
(1-5)
(1-5)
Gleason sum:
(2-10)
These are the two components that are combined to obtain the Gleason sum.
98 = unsatisfactory
99 = no grade possible
Based on biopsy (including TURP)
Primary:
Secondary:
(1-5)
(1-5)
Gleason sum:
(2-10)
These are the two components that are combined to obtain the Gleason sum.
98 = unsatisfactory
99 = no grade possible
Number positive:
Number of cores:
SWOG Patient ID
Patient Initials
23968


SOUTHWEST ONCOLOGY GROUP
S9921 LOCAL PROSTATE CARCINOMA PRESTUDY
3/15/2006
(L, F M)
Page 3 of 3
Comments:
SWOG Study No. S 9 9 2 1
Registration Step 1
Description:
Did the patient receive hormonal therapy prior to radical prostatectomy?
No
Yes
PRIOR TREATMENT RELATED TO THIS CANCER
Did the patient have a radical prostatectomy (MUST be Yes for patient to be eligible)?
No
Yes
Date of radical prostatectomy:
/
/
Were margins positive?
No
Yes
Did the patient receive hormonal therapy after radical prostatectomy but prior to S9921 registration?
No
Yes, description:
Date of first treatment with LHRH analog:
/
/
Date of most recent LHRH analog injection:
/
/
Specified dose duration of most recent LHRH analog injection:
1 month
3 month
4 month
Other, specify
Did the prior hormonal therapy include an LHRH analog?
No
Yes, description:
Was LHRH analog treatment continuous from first administration to S9921 registration?
Yes
No, explain
No
Yes
Did the patient receive any prior radiation therapy in the treatment of this cancer (MUST be No for patient to be
eligible)?
LABORATORY VALUES
PSA value prior to radical prostatectomy:
.
ng/ml
Date of PSA prior to radical prostatectomy:
/
/
.
ng/ml
PSA value after radical prostatectomy (prior to the start of post-surgical hormone therapy if already started OR within
28 days prior to registration if post-surgical hormone therapy not already started):
Date of PSA after radical prostatectomy:
/
/
Testosterone:
Date of testosterone:
/
/
ng/dl
(within 28 days prior to registration)
If patient had prior hormonal therapy, testosterone value prior to therapy:
Date of testosterone:
/
/
Testosterone ILLN:
ng/dl
ng/dl
SWOG Patient ID
Patient Initials
23968


SOUTHWEST ONCOLOGY GROUP
S9921 PSA REPORTING FORM
3/15/2006
Comments:
SWOG Study No. S 9 9 2 1
SWOG Patient ID
Registration Step 1
Patient Initials
(L, F M)
Physician
Institution / Affiliate
Instructions:  Include all measurements of PSA  taken since the last reported form.  See the Study Calendar (Section 9.0) for
collection schedules of PSA.  Note PSA measurements taken prior to S9921 registration on the S9921 Prestudy form.  All dates are
MONTH, DAY, YEAR.  Explain any blank fields or dates in the Comments section.  Please mark AMENDED data in red and write
AMENDED at the top of the form.
Page 1 of 1
Participating Group:  Group Name/Study No./Patient ID
/
/
PSA
4.
/
/
5.
/
/
6.
/
/
.
PSA value(s) (ng/ml)
.
.
.
.
.
(PSA)
Date of assessment(s)
1.
/
/
2.
/
/
3.
/
/
59255


SOUTHWEST ONCOLOGY GROUP
S9921 TESTOSTERONE REPORTING FORM
3/15/2006
Comments:
SWOG Study No. S 9 9 2 1
SWOG Patient ID
Registration Step 1
Patient Initials
(L, F M)
Physician
Institution / Affiliate
Instructions:  Include all measurements of Testosterone taken since the last reported form.  See the Study Calendar (Section 9.0) for
collection schedules of Testosterone.  Note Testosterone measurements taken prior to S9921 registration on the S9921 Prestudy
form.  All dates are MONTH, DAY, YEAR.  Explain any blank fields or dates in the Comments section.  Please mark AMENDED data
in red and write AMENDED at the top of the form.
Page 1 of 1
Participating Group:  Group Name/Study No./Patient ID
/
/
(TESTOS)
Testosterone
Testosterone value(s) (ng/dl)
Date of assessment(s)
1.
/
/
2.
/
/
3.
/
/
25939


 SOUTHWEST ONCOLOGY GROUP
S9921 TREATMENT FORM
SWOG Patient ID
3/15/2006
Institution/Affiliate
Physician
(L, F M)
Patient Initials
Page 1 of 1
Participating Group:  Group Name/Study No./Patient ID
/
/
Comments:
LHRH Analogue (Zoladex): (Report injections received in this reporting period.  Patient may have received 1-3
injections depending on dose used.)
1.
Injection
2.
Injection
3.
Injection
Date:
/
/
Date:
/
/
Date:
/
/
Dose:
.
mg
mg
Dose:
.
Dose:
.
mg
Radiotherapy:
Has patient received any radiotherapy to date while on study?
Yes
No
If RT initiated in this reporting interval, start date:
/
/
If RT completed in this reporting interval, date of completion:
/
/
Total dose received in this reporting period:
cGy
TREATMENT
(TX9921)
SWOG Study No. S 9 9 2 1
Registration Step 1
STATUS
Vital Status:
Alive
Dead
Date of Last Contact or Death:
/
/
(submit Notice of Death)
Has the patient progressed per the definition in Section 10.0 of the protocol?
No
Yes
(submit Follow-Up Form)
Reporting interval stop date:
/
/
Reporting interval start date:
/
/
(specify in comments)
(specify in comments)
No
Yes, planned (per protocol guidelines)
Yes, unplanned (not per protocol guidelines)
Were there any dose modifications or additions/ omissions to protocol treatment?
Anti-Androgen (Casodex):
Has the patient been receiving daily anti-androgen during the specified interval?
Yes
No, explain:
Instructions:  This form is for both Arm 1 and Arm 2.  Please complete this form and submit after every 3 months of protocol
hormonal therapy.  Note hormonal therapy given prior to S9921 registration on the S9921 Prestudy form.  Note the S9921
Chemotherapy Treatment Form must also be submitted for Arm 2 patients while on chemotherapy.  All dates are MONTH, DAY,
YEAR.  Explain any blank dates or fields in the Comments section.  Place an   X   in appropriate boxes.  Circle AMENDED items in red
and write AMENDED across top of form.
38859


 SOUTHWEST ONCOLOGY GROUP
S9921 CHEMOTHERAPY TREATMENT FORM
SWOG Patient ID
3/15/2006
Institution/Affiliate
Physician
(L, F M)
Patient Initials
Page 1 of 1
Participating Group:  Group Name/Study No./Patient ID
/
/
Comments:
Instructions: This form is for Arm 2 patients during the chemotherapy phase of protocol treatment.  Please complete this form and
submit following the 3rd and 6th cycles of chemotherapy (1 cycle = 21 days).  Note that the S9921 Treatment Form must also be
completed every 3 months while on protocol hormonal therapy.  All dates are MONTH, DAY, YEAR.  Explain any blank dates or fields
in the Comments section.  Place an   X   in appropriate boxes.  Circle AMENDED items in red and write AMENDED across top of form.
Date Form Completed:
/
/
CHEMOTHERAPY
(Report cycles 1-3 or 4-6)
Cycle Number:
Did the patient receive mitoxantrone this cycle?
Yes
No
Did the patient receive prednisone this cycle?
Yes
No
Cycle Number:
Did the patient receive mitoxantrone this cycle?
Yes
No
Did the patient receive prednisone this cycle?
Yes
No
Cycle Number:
Did the patient receive mitoxantrone this cycle?
Yes
No
Did the patient receive prednisone this cycle?
Yes
No
(TX9921C)
SWOG Study No. S 9 9 2 1
Registration Step 1
Vital Status:
Alive
Dead
STATUS
Has the patient progressed per the definition in Section 10.0 of the protocol?
No
Yes
Date of Last Contact or Death:
/
/
(submit Notice of Death)
(submit Follow-Up Form)
(specify in comments)
(specify in comments)
No
Yes, planned (per protocol guidelines)
Yes, unplanned (not per protocol guidelines)
Were there any dose modifications or additions/ omissions to protocol treatment?
Total dose:
If Yes, Date of injection:
/
/
mg
BSA:
.
m2
Total dose:
If Yes, Date of injection:
/
/
mg
Total dose:
If Yes, Date of injection:
/
/
mg
BSA:
.
m2
BSA:
.
m2
61544


 SOUTHWEST ONCOLOGY GROUP
S9921 ADVERSE EVENT SUMMARY FORM
SWOG Patient ID
SWOG Study No. S 9 9 2 1
Registration Step 1
Patient Initials
Institution/Affiliate
Physician
(L, F M)
3/15/2006
Participating Group:  Group Name/Study No./Patient ID
/
/
Page 1 of 1
TOXICITY
No
Yes
Date of most recent toxicity assessment:
/
/
Were toxicities assessed during this time period?
Mark box if toxicities were assessed but none were seen.  Otherwise indicate grades below.
CTC 2.0
Code
Toxicity
CA50
Hypertension
CA51
Hypotension
EN20
Gynecomastia
EN30
Hot flashes
FL30
Sweating
FL40
Fatigue/malaise/lethargy
GI00
Nausea
GI10
Vomiting
GI20
Diarrhea without colostomy
GI30
Constipation/bowel obstruction
GI60
Stomatitis/pharyngitis
GU00
Incontinence
GU03
Urinary frequency/urgency
HE00
Leukopenia
HE30
Neutropenia/granulocytopenia
ME31
Hyperglycemia
MS00
Muscle weakness (not neuro)
Grade
(1 - 5)
Treatment
Relation*
CTC 2.0
Code
Toxicity
Grade
(1 - 5)
Treatment
Relation*
MS31
Arthritis
NR12
Anxiety/agitation
NR13
Depression
NR60
Sensory neuropathy
NR92
Insomnia
PA00
Headache
PA30
Abdominal pain/cramping
PA40
Chest pain, not cardio or pleur
PA99
Pain - other
SK11
Rash/desquamation
SK90
Alopecia
SX00
Libido loss
SX60
Erectile impotence
* Treatment Relation codes:  1-unrelated
2-unlikely
3-possible
4-probable
5-definite
Comments: (Please explain any "other" adverse events reported above, e.g., PA99 Pain-other)
Other Toxicities (specify):
Instructions:
Arm 1 - Please complete this form and submit after every 3 months of protocol hormonal therapy.
Arm 2 - Please complete and submit this form after the 3rd and 6th cycles of chemotherapy (1 cycle = 21 days)
summarizing all cycles in the reporting period.  Continue to complete and submit this form every 3 
months while on protocol hormonal therapy.
Report all adverse events observed.  Document the worst Grade seen during the reporting period.  Do not code a condition existing
prior to registration as an adverse event unless it worsens.  Category lists may not include all adverse events from that category.
Record any observed adverse events not listed on the blank lines at the end.  All dates are MONTH, DAY, YEAR.  Explain any blank
dates or fields in the Comments section.  Place an   X   in appropriate boxes.  Circle AMENDED items in red and write AMENDED
across top of form.
27242


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9/1/2003
Comments:
SOUTHWEST ONCOLOGY GROUP
OFF TREATMENT NOTICE
SWOG Patient ID
SWOG Study No. S
Registration Step
Physician
Institution / Affiliate
Off Treatment Reason
Treatment completed per protocol criteria
Medically required, due to toxicity, specify:
Patient refused, due to toxicity, specify:
Patient refused, other than toxicity, specify:
Progression or relapse.  Sites:
Death (submit Notice of Death form)
Other, specify:
Treatment Start Date
(If more room is needed, please continue on a separate page)
Off Treatment Date
Date of completion, progression, death or decision to discontinue therapy:
/
/
Will patient receive further treatment?
No
Yes, specify:
Unknown
Date of Last Contact (or death):
/
/
(select one):
Vital Status:
Alive
Dead (submit Notice of Death form)
All dates are MONTH, DAY, YEAR.  Explain any blank fields or blank dates in the Comments section.
Place an   X   in appropriate boxes.  Circle AMENDED items in red.
Treatment End Date
Regimen or Procedure or Site(s)
Systemic Therapy:
List regimens, start and end dates.  For multidrug regimens, do not list individual drugs separately;
end date would be the date all drugs in the regimen were discontinued.
Surgery:
List type of surgery, and in the "end date" column, the date of surgery.
Radiation:
List sites, start and end dates (inclusive of boosts and implants).
(L, F M)
Patient Initials
Instructions:
For each registration step, submit this form within 2 weeks after completion (or discontinuation) of
treatment.
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
Page 1 of 1
Participating Group:  Group Name/Study No./Patient ID
/
/
8756


9/1/2003
Comments:
SOUTHWEST ONCOLOGY GROUP
NOTICE OF DEATH
Autopsy?
No
Yes
Unknown
If cancer was the primary cause or if cancer possibly or definitely contributed to death, and the patient
had had multiple tumor types, specify those which were causes of death:
No
Primary Cause
Contributory
Possible
Unknown
Any cancer (select one):
CAUSES OF DEATH
(month / day / year)
Date of Death:
/
/
SWOG Patient ID
Most Recent SWOG Study No. S
Physician
Institution / Affiliate
(L, F M)
Patient Initials
Cancer of most recent SWOG study, specify cancer:
Cancer of other SWOG study, specify cancer:
Other cancer, specify:
If Primary Cause, Contributory or Possible, specify treatment and toxicity:
No
Primary Cause
Contributory
Possible
Unknown
Toxicity from disease related treatment (select one):
If Primary Cause, Contributory or Possible, specify:
No
Primary Cause
Contributory
Possible
Unknown
Non-cancer and non-treatment related causes (select one):
Source(s) of death information:
Autopsy report
Medical record / Death certificate
Physician
Relative or friend
Other, specify:
Instructions:  Answer all questions and explain any blank fields or blank dates in the Comments section.
Place an   X   in appropriate boxes.  Circle AMENDED items in red.
Participating Group:  Group Name/Study No./Patient ID
/
/
Page 1 of 1
49467


 
S9921 
 
Page 57 
 
Revised 4/15/00 
 
Amended 2/14/06 
 
Revised 2/1/07 
 
 
 
 
 
19.0 
APPENDIX 
 
19.1 
This study will utilize the CTC (NCI Common Toxicity Criteria) version 2.X for toxicity 
and Adverse Event reporting.  A copy of the CTC version 2.X can be downloaded from 
the CTEP home page (http://ctep.info.nih.gov).  All appropriate treatment areas 
should have access to a copy of the CTC version 2.X. 
 
19.2 
Expanded Participation Project (EPP) Instructions 
 
19.3 
Returned Medication Packing Slip  
 
19.4 
S9921 Novantrone® Drug Request Form  
 
19.5 
Determination of Expedited Adverse Event Reporting Requirements 
 
19.6 
CTSU Regulatory and Monitoring Guidelines 
 
 


 
S9921 
 
Page 58 
 
Amended 2/14/06 
 
 
 
 
 
     
 
 
 
19.2 
Expanded Participation Project (EPP) Instructions. 
 
ADJUVANT ANDROGEN DEPRIVATION VERSUS MITOXANTRONE PLUS PREDNISONE  
PLUS ANDROGEN DEPRIVATION IN SELECTED HIGH RISK PROSTATE CANCER PATIENTS  
FOLLOWING RADICAL PROSTATECTOMY  
 
PHASE III  
 
1.0 
EPP Randomization and Registration Procedures 
  
I.   
EPP institutions will enroll a patient on-line through the Clinical Trials Management Unit 
(CTMU).  Questions pertaining to eligibility criteria should be directed to the CTMU, 
medical questions should be directed to the Study Chair. 
 
II.  
A signed HHS 310 form documenting the Institutional Review Board (IRB) approval for 
this study must be on file at the CTMU before the EPP institution can enter a patient. IRB 
approval date must be less than one year prior to the date of registration.   
 
III.  
Once eligibility is confirmed, the CTMU will contact SWOG to randomize the patient.  The 
CTMU will notify the institution by an email upon successful registration with SWOG.  In 
addition SWOG will forward confirmation of randomization and treatment assignment to 
the CTMU for routing to the participating institutions.  Please check for errors, and submit 
any corrections in writing to the CTMU. Treatment should start within one working day 
after registration. 
 
 
2.0 
EPP Data Submission 
 
Data must be submitted electronically directly to the CTMU according to the following schedule: 
 
FORM  
 
TIME OF SUBMISSION 
1.   SWOG Registration Form   
At enrollment 
 
2.  Prostate Cancer Prestudy Form** 
          (Pathology Report*)  
 
Within 14 days of enrollment 
 
3.  EPP Toxicity Form 
 
 Months 1, 2, 3, and every three months while on 
protocol therapy  
 
4.  EPP Follow-up Form** 
 
Every 3 months while on protocol treatment and every 
6 months after completion of protocol treatment until 
death 
 
5. EPP Recurrence Form  
 
At the time of recurrence 


 
S9921 
 
Page 59 
 
Amended 2/14/06 
 
 
 
 
 
     
 
 
 
FORM  
 
TIME OF SUBMISSION 
 
6.  EPP 
Chemotherapy/Immunotherapy/Hormonal          
Therapy Form 
 
 
At the completion of protocol therapy 
 
7.  EPP Off-Treatment Form** 
 
 
At the completion of all protocol therapy 
 
8.  EPP Notice of Secondary Malignancy 
Form  
 
Within 10 days of diagnosis 
 
9.  EPP Death Form 
 
Within 7 days of knowledge of event 
* Fax a copy of the Pathology Report to the CTMU Attn: EPP Protocol Monitor 301-299-3991  
** These forms are to be submitted according to the above schedule for all patients who never started 
treatment. 
 
 
3.0 
EPP Adverse Drug Reaction 
 
For EPP Institutions, all ADR’s are to be faxed to the CTMU (Attn: EPP Protocol Monitor 301-
299-3991) using the Adverse Reaction (ADR) Form for Investigational Drugs.  These reports will 
be reviewed and directed to the Southwest Oncology Group and appropriate regulatory offices.  
ADR reporting is based on the revised NCI Common Toxicity Criteria (version 2.X).   
+ 
ADRs will be faxed to the CTMU based on the following adverse event reporting  
requirements table: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AGENTS 
 
1 
 
2 
 
3 
 
4 
 
5 
 
Commercial Agents 
        Expected AE  
 
 
----- 
 
 
----- 
 
 
----- 
 
 
----- 
 
 
----- 
 
Commercial Agents 
        Unexpected AE 
 
 
----- 
 
 
----- 
 
 
----- 
 
 
ADR 
 
 
ADR 
ADR = Adverse Drug Reaction Report (within 7 days) 
 
 
ADR reports should be submitted via fax within 7 days of the event.  These will be forwarded to 
the NCI and the Coordinating Group within 3 working days.  All ADRs should be reported to the 
local IRB. 
 
     GRADE 


 
S9921 
 
Page 60 
 
Amended 2/14/06 
 
 
 
 
 
     
 
For commercially available drugs, written reporting of any increased incidence of a known ADR is 
also required in addition to grade 4 and 5 toxicities. 
 
All toxicities, including those with separate reporting requirements described above, must be 
reported on the Toxicity Form.  Deaths are required to be reported via the Death Form within 7 
days of knowledge of the event. 
 
4.0 
EPP Secondary Malignancy Reporting 
 
Investigators are required to report secondary malignancies occurring on or following treatment 
on NCI-sponsored protocols using commercial drugs.  Reporting of cases of secondary 
AML/MDS is to be performed using the NCI/CTEP Secondary AML/MDS Report Form.  This form 
should be used in place of DCT Adverse Reaction (ADR) Form for reporting this toxicity.  All 
other secondary malignancies should be reported using the form DCT Adverse Reaction Form. 
The EPP Notice of Secondary Malignancy must also be completed for all cases of secondary 
malignancy. 
 


S9921
Page 61
Amended 2/14/06
19.3
UVI, Inc.
Revised 4/3/06


Appended 4/15/00 
Revised 11/1/02 
S9921 
Revised 5/15/00 
Revised 5/15/03 
Page 62 
Amended 7/1/00 
Revised 9/1/03 
Amended 2/14/06 
Revised 7/15/01 
 
 
 
 
S9921 APPENDIX 19.4 
 
 
Novantrone Drug Request Form 
 
 
 
 
 
 
Requested By: 
 
Dr.    
   Dr.’s State License #*     
 
Institution    
   Current IRB Approval Date    
 
 
Principal Investigator    
 
 
 
 
 
 
Institution Contact    
 
 
 
 
 
 
Telephone    
   Fax     
 
 
 
 
 
*Note:  Actual copy of license is required from physicians from Delaware, the District of Columbia, South Dakota, 
Mississippi and Puerto Rico.  For other states, please indicate # only. 
 
 
Novantrone will be shipped Monday through Wednesday. 
A minimum of two days notice is required. 
 
Date Drug Needed By: 
 
 
            
 
 
 
  
 
  Ship to:    
 
Name    
 
 
 
Address*    
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Please do not use PO Box numbers 
 
 
Novantrone (25mg) 
 
SWOG Patient Sequence Number(s) 
REQUIRED FOR ALL DRUG SHIPMENTS 
 
# of Vials Required 
 
 
 
Signature 
 
 
 
 
 
 
 
Date 
 
 
 
Fax completed, signed and dated form to:  Priority Healthcare Corporation 
866-203-4684 
Questions?  Please call Charlie Drayton at 407/804-6743  
or Greg Friedman at 407/833-4500 (Priority Healthcare) 


 
S9921 
 
Page 63 
 
Amended 2/14/06 
 
 
 
 
 
     
 
19.5 
Determination of Expedited Adverse Event Reporting Requirements 
 
Adverse event data collection and reporting, which are required as part of every clinical 
trial, are done to ensure the safety of patients enrolled in the studies as well as those 
who will enroll in future studies using similar agents. Adverse events are reported in a 
routine manner at scheduled times during a trial. (Directions for routine reporting are 
provided in Section 14.0.) Additionally, certain adverse events must be reported in an 
expedited manner to allow for more timely monitoring of patient safety and care. 
Expedited adverse event reporting principles and general guidelines follow; specific 
guidelines for expedited adverse event reporting on this protocol are found in Section 
16.0. 
 
Reporting requirements may include the following considerations: 1) whether the patient 
has received an investigational or commercial agent; 2) the characteristics of the adverse 
event including the grade (severity), the relationship to the study therapy (attribution), 
and the prior experience (expectedness) of the adverse event; 3) the Phase (I, II, or III) of 
the trial; and 4) whether or not hospitalization or prolongation of hospitalization was 
associated with the event.  
 
An investigational agent is a protocol drug administered under an Investigational New 
Drug Submission (IND). In some instances, the investigational agent may be available 
commercially, but is actually being tested for indications not included in the approved 
package label.  
 
Commercial agents are those agents not provided under an IND but obtained instead 
from a commercial source. The NCI, rather than a commercial distributor, may on some 
occasions distribute commercial agents for a trial. 
 
When a study includes both investigational and commercial agents, the following rules 
apply. 
 
• 
Concurrent administration: When an investigational agent(s) is used in combination 
with a commercial agent(s), the combination is considered to be investigational and 
expedited reporting of adverse events would follow the guidelines for investigational 
agents. 
• 
Sequential administration: When a study includes an investigational agent(s) and a 
commercial agent(s) on the same study arm, but the commercial agent(s) is given for 
a period of time prior to starting the investigational agent(s), expedited reporting of 
adverse events that occur prior to starting the investigational agent(s) would follow 
the guidelines for commercial agents. Once therapy with the investigational agent(s) 
is initiated, all expedited reporting of adverse events should follow the investigational 
guidelines. 
 
Steps to determine if an adverse event is to be reported in an expedited manner 
 
Step 1: Identify the type of event using the NCI Common Terminology Criteria for 
Adverse Events (CTCAE). The CTCAE provides descriptive terminology and a grading 
scale for each adverse event listed. A copy of the CTCAE can be downloaded from the 
CTEP home page (http://ctep.cancer.gov). Additionally, if assistance is needed, the NCI 
has an Index to the CTCAE that provides help for classifying and locating terms. All 
appropriate treatment locations should have access to a copy of the CTCAE. 


 
S9921 
 
Page 64 
 
Amended 2/14/06 
 
 
 
 
 
     
 
Step 2: Grade the event using the NCI CTCAE version specified. 
 
Step 3: Determine whether the adverse event is related to the protocol therapy 
(investigational or commercial). Attribution categories are as follows: Unrelated, Unlikely, 
Possible, Probable, and Definite. 
 
Step 4: Determine the prior experience of the adverse event. Expected events are those 
that have been previously identified as resulting from administration of the agent. An 
adverse event is considered unexpected, for expedited reporting purposes only, when 
either the type of event or the severity of the event is not listed in  
 
• 
the current NCI Agent-Specific Adverse Event List (for treatments using agents 
provided under an NCI-held IND); 
• 
the drug package insert (for treatments with commercial agents only); 
• 
Section 3.0 of this protocol. 
 
Step 5: Review Table 16.1 in the protocol to determine if there are any protocol-specific 
requirements for expedited reporting of specific adverse events that require special 
monitoring.  
 
Step 6: Determine if the protocol treatment given prior to the adverse event included an 
investigational agent(s), a commercial agent(s), or a combination of investigational and 
commercial agents. 
 
NOTE: If the patient received at least one dose of investigational agent, follow the 
guidelines in Table 16.1. If no investigational agent was administered, follow the 
guidelines in Table 16.2. 
 
NOTE: This includes all events that occur within 30 days of the last dose of protocol 
treatment. Any event that occurs more than 30 days after the last dose of treatment and 
is attributed possibly, probably, or definitely to the agent(s) must be reported according to 
the instructions above.  


 
S9921 
 
Page 65 
 
Appended 2/1/07 
 
 
 
 
 
     
 
19.6 
CTSU Regulatory and Monitoring Guidelines 
 
Study Audit 
 
To assure compliance with Federal regulatory requirements [CFR 21 parts 50, 54, 56, 
312, 314 and HHS 45 CFR 46] and National Cancer Institute (NCI)/ Cancer Therapy 
Evaluation Program (CTEP) Clinical Trials Monitoring Branch (CTMB) guidelines for the 
conduct of clinical trials and study data validity, all protocols approved by NCI/CTEP that 
have patient enrollment through the CTSU are subject to audit. 
 
Responsibility for assignment of the audit will be determined by the site’s primary 
affiliation with a Cooperative Group or CTSU. For Group-aligned sites, the audit of a 
patient registered through CTSU will become the responsibility of the Group receiving 
credit for the enrollment. For CTSU Independent Clinical Research Sites (CICRS), the 
CTSU will coordinate the entire audit process. 
 
For patients enrolled through the CTSU, you may request the accrual be credited to any 
Group for which you have an affiliation provided that Group has an active clinical trials 
program for the primary disease type being addressed by the protocol. (e.g., NSABP 
members may only request credit for protocols pertaining to breast or colorectal 
cancers).  Registrations to protocols for other disease sites may still take place through 
CTSU without receiving credit for your NSABP activities.  Per capita reimbursement will 
be issued directly from CTSU. 
 
Details on audit evaluation components, site selection, patient case selection, materials 
to be reviewed, site preparation, on-site procedures for review and assessment, and 
results reporting and follow-up are available for download from the CTSU Operations 
Manual located on the CTSU Member Web site. 
 
Health Insurance Portability and Accountability Act of 1996 (HIPAA) 
 
The HIPAA Privacy Rule establishes the conditions under which protected health 
information may be used or disclosed by covered entities for research purposes. 
Research is defined in the Privacy Rule referenced in HHS 45 CFR 164.501. Templated 
language addressing NCI-U.S. HIPAA guidelines are provided in the HIPAA 
Authorization Form located on the CTSU website.  
 
The HIPAA Privacy Rule does not affect participants from outside the United States. 
Authorization to release Protected Health Information is NOT required from patients 
enrolled in clinical trials at non-US sites. 
 
Clinical Data Update System (CDUS) Monitoring 
 
This study will be monitored by the Clinical Data Update System (CDUS) Version 3.0.  
Cumulative CDUS data will be submitted quarterly to CTEP by electronic means. The 
sponsoring Group fulfills this reporting obligation by electronically transmitting to CTEP 
the CDUS data collected from the study-specific case report forms.