Clinical trial NCT00981656
Conditions: Bladder Cancer
Keywords: stage I bladder cancer transitional cell carcinoma of the bladder
Sponsor: Radiation Therapy Oncology Group
Start date: 2009-11-01; Completion date: 2023-08-15
Enrollment: 37 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as cisplatin, mitomycin C, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy together with cisplatin may kill more tumor cells.

PURPOSE: This phase II trial is studying how well radiation therapy given together with chemotherapy works in treating patients with stage I bladder cancer.

Detailed description:
After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and annually thereafter until termination of the study.

Arms: arm 1: Concurrent three-dimensional conformal radiation therapy (3DCRT) and radiosensitizing chemotherapy (CT) consisting of either cisplatin alone or the combination of mitomycin and 5-fluorouracil. Protocol treatment must begin with 15 weeks after a transurethral resection of the tumor (TURBT).
Interventions: intervention 1: cisplatin intervention 2: 5-fluorouracil intervention 3: Mitomycin intervention 4: Three-Dimensional Conformal Radiation Therapy
Intervention descriptions: intervention 1: 60-minute intravenous (IV) infusion of 15 mg/m\^2 on days 1, 2, 3, 15, 16, 17, 29, 30, and 31 of radiation treatment. intervention 2: Continuous IV infusion of 500 mg/m\^2/24 hrs for 5 consecutive days during weeks 1 and 4 of radiation treatment. intervention 3: IV bolus dose of 12 mg/m\^2 on day 1 of radiation treatment. intervention 4: Total dose to the gross bladder volume of 61.2 Gy as 34 daily fractions 5 days/week, for approximately 7 weeks.

Protocol documents:
Prot_SAP_000.pdf: 
NRG ONCOLOGY 
Radiation Therapy Oncology Group 
 
RTOG 0926 
 
(ClinicalTrials.gov NCT #: 00981656) 
 
 
A Phase II Protocol for Patients with Stage T1 Bladder Cancer to Evaluate 
Selective Bladder Preserving Treatment by Radiation Therapy Concurrent 
with Radiosensitizing Chemotherapy Following a Thorough Transurethral 
Surgical Re-Staging 
 
 
Amendment 5:  February 1, 2019 


For Protocol Amendment 5 to:  RTOG 0926, A Phase II Protocol For Patients With Stage T1 Bladder Cancer To 
Evaluate Selective Bladder Preserving Treatment By Radiation Therapy Concurrent With Radiosensitizing 
Chemotherapy Following A Thorough Transurethral Surgical Re-Staging 
 
 
NCI/Local Protocol #:  RTOG-0926 / RTOG 0926 
 
 
NCI Protocol Version Date:  February 01, 2019 
 
 
 
Section 
Change 
Document Footer 
The protocol version date was updated 
Document 
History Table 
The amendment was added 
CTSU Contact 
Information table 
5.0 
5.2 
5.3 
5.4 
 
Updated per the NCTN/CTSU standard text  
7.9 
Due to CTEP’s migration from CTCAE v 4.0 to CTCAE v 5.0, this section was 
revised to reflect the following: 
o 
CTCAE v 4.0 will be utilized for AE reporting until March 31, 2018; 
o 
Beginning April 1, 2018, CTCAE version 5.0 will be utilized for CTEP-AERS 
reporting; 
o 
All study case report forms will continue to use CTCAE version 4.0. 
 
10.3 
 
This section has been deleted as the reimbursement information is posted on the 
CTSU website. 
 
10.4 
Section 10.4 has been renumber to 10.3 and the first sentence was deleted, as 
the link is no longer valid. 
12.0 
Updated per the NCTN/CTSU standard text 
Informed 
Consent 
No Changes to the text of the sample consent; the version date of the consent 
was changed to be consistent with the amended protocol 
 
 
 
 
 
 
 
 
 


1  
RTOG 0926; version date February 01, 2019 
 
 
NRG ONCOLOGY 
RTOG 0926 
 
A PHASE II PROTOCOL FOR PATIENTS WITH STAGE T1 BLADDER CANCER TO 
EVALUATE SELECTIVE BLADDER PRESERVING TREATMENT BY RADIATION 
THERAPY CONCURRENT WITH RADIOSENSITIZING CHEMOTHERAPY FOLLOWING A 
THOROUGH TRANSURETHRAL SURGICAL RE-STAGING 
 
Study Chairs (3/6/2015) 
(3/31/14) 
Co-Principal Investigator/Urology 
Douglas M. Dahl, MD 
Massachusetts General Hospital 
55 Fruit Street 
Boston, MA 02114 
Phone: 617-726-0875/Fax: 617-726-6131 
E-mail: ddahl@partners.org 
Co-Principal Investigator/Radiation Oncology 
William U. Shipley, MD, FACR, FASTRO 
Andres Soriano Distinguished Professor of 
Radiation Oncology, 
Harvard Medical School 
Department of Radiation Oncology 
100 Blossom Street - Cox 3 
Massachusetts General Hospital 
Boston, MA 02114 
Phone: 617-724-1614/857-205-2341 
Fax: 617-726-3603 
E-mail: WShipley@partners.org 
Medical Oncology 
M. Dror Michaelson, MD PhD 
Medical Oncology 
Massachusetts General Hospital 
55 Fruit Street, Yawkey 7E 
Boston, MA 02114 
Phone: 617 726-1594/Fax: 617 726-3440 
E-mail: dmichaelson1@partners.org 
 
Pathology 
Chin-Lee Wu, MD, PhD 
Massachusetts General Hospital 
55 Fruit Street, Warren 333A 
Boston, MA 02114 
Phone: 617-726-8485/Fax:617-724-7803 
E-mail: cwu2@partners.org 
 
Medical Physics 
William Parker, MSc, FCCPM 
McGill University Health Centre L5-112 
1650 ave Cedar 
Montreal, Quebec, CANADA  
H3G 1A4 
Phone: 514-934-8052/Fax: 514-934-8229 
E-mail: william.parker@mcgill.ca 
Senior Statistician  
Kathryn Winter, MS 
NRG Oncology 
1818 Market Street, Suite 1720 
Philadelphia, PA 19103 
Phone: 215-574-3198/Fax: 215-928-0153 
E-mail: winterk@nrgoncology.org 
 
 
Protocol Agent 
Agent 
Supply 
NSC # 
IND # 
Cisplatin 
Commercial 
 
N/A 
Exempt 
5FU 
Mitomycin 
 
Participating Sites: 
 U.S. and Canada 
 Approved International Member Sites 
 
 


2  
RTOG 0926; version date February 01, 2019 
 
 
NRG ONCOLOGY 
 
RTOG 0926 
 
A PHASE II PROTOCOL FOR PATIENTS WITH STAGE T1 BLADDER CANCER TO 
EVALUATE SELECTIVE BLADDER PRESERVING TREATMENT BY RADIATION 
THERAPY CONCURRENT WITH RADIOSENSITIZING CHEMOTHERAPY FOLLOWING A 
THOROUGH TRANSURETHRAL SURGICAL RE-STAGING 
 
 
 
 
 
 
 
 
 
Document History 
 
Version/Update Date 
Broadcast Date 
Amendment 5 
February 1, 2019 
N/A 
Amendment 4 
April 20, 2015 
April 27, 2015 
Amendment 3 
March 6, 2015 
TBD 
Amendment 2 
March 31, 2014 
April 28, 2014 
Update 
December 17, 2013 
December 17, 2013 
Update 
May 15, 2012 
May 15, 2012 
Update 
April 26, 2012 
April 26, 2012 
Amendment 1 
April 6, 2012 
April 26, 2012 
Update 
November 11, 2009 
November 11, 2009 
Activation 
October 26, 2009 
November 11, 2009 
 
 
NRG Oncology 
1-800-227-5463, ext. 4189 
 
 
  
 
 
 
 
 
 
This protocol was designed and developed by NRG Oncology.  It is intended to be 
used only in conjunction with institution-specific IRB approval for study entry.  
No other use or reproduction is authorized by NRG Oncology nor does NRG 
Oncology assume any responsibility for unauthorized use of this protocol. 


3  
RTOG 0926; version date February 01, 2019 
 
 
NRG ONCOLOGY 
RTOG 0926   
 
A PHASE II PROTOCOL FOR PATIENTS WITH STAGE T1 BLADDER CANCER TO 
EVALUATE SELECTIVE BLADDER PRESERVING TREATMENT BY RADIATION 
THERAPY CONCURRENT WITH RADIOSENSITIZING CHEMOTHERAPY FOLLOWING A 
THOROUGH TRANSURETHRAL SURGICAL RE-STAGING   
 
 
 
CANCER TRIAls SUPPORT UNIT (CTSU) CONTACT INFORMATION (01-Feb-2019) 
To submit site registration 
documents: 
For patient enrollments:  
Submit study data  directly 
to the Lead Cooperative 
Group unless otherwise 
specified in the protocol:  
Regulatory documentation must 
be submitted to the CTSU via 
the Regulatory Submission 
Portal. 
Regulatory Submission Portal: 
(Sign in at www.ctsu.org,            
and select the Regulatory 
Submission sub-tab under the 
Regulatory tab.)  
 
Institutions with patients waiting 
that are unable to use the 
Portal should alert the CTSU 
Regulatory Office immediately 
at 1-866-651-2878 to receive 
further instruction and support. 
 
Contact the CTSU Regulatory 
Help Desk at 1-866-651-2878 
for regulatory assistance. 
Please refer to the patient 
enrollment section of the protocol 
for instructions on using the 
Oncology Patient Enrollment 
Network (OPEN) which can be 
accessed at 
https://www.ctsu.org/OPEN_SYST
EM/ or https://OPEN.ctsu.org. 
 
Contact the CTSU Help Desk with 
any OPEN-related questions at 
ctsucontact@westat.com. 
 
NRG Oncology 
1818 Market Street 
Suite 1720 
Philadelphia, PA 19103 
 
Submit data electronically via 
the NRG Oncology/RTOG web 
site, www.rtog.org  
 
Do not submit study data or 
forms to CTSU Data 
Operations. Do not copy the 
CTSU on data submissions.   
The most current version of the study protocol and all supporting documents must be downloaded 
from the protocol-specific Web page of the CTSU Member Web site located at https://www.ctsu.org.  
Access to the CTSU members’ web site is managed through the Cancer Therapy and Evaluation 
Program - Identity and Access Management (CTEP-IAM) registration system and requires user log on 
with CTEP-IAM username and password.  : Permission to view and download this protocol and its 
supporting documents is restricted and is based on person and site roster assignment housed in the 
CTSU RSS.   
 
For patient eligibility or treatment-related questions Contact the Study PI of the Lead Protocol 
Organization. 
For non-clinical questions (i.e. unrelated to patient eligibility, treatment, or clinical 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 Web site is located at https://www.ctsu.org 


4  
RTOG 0926; version date February 01, 2019 
 
 
Table of Contents  
 
SCHEMA ....................................................................................................................................................................6 
ELIGIBILITY CHECKLIST (4/20/15) ...........................................................................................................................7 
   1.0       INTRODUCTION ...................................................................................................................................... 11 
   1.1        Background for Evaluating Trimodality Therapy in Patients with Aggressive Forms of Non-Muscle              
Invading Bladder Cancer Who Have Failed Other Conservative Treatments (3/31/14) ......................................... 11 
1.2 
 Rationale for Evaluating Patient Tolerance for Whole Bladder Irradiation to 61.2 Gy with Concurrent       
Chemotherapy (4/6/12) ........................................................................................................................................ 12 
1.3 
Biomarkers in Bladder Cancer ................................................................................................................. 12 
2.0 
OBJECTIVES .......................................................................................................................................... 12 
2.1 
Primary Objectives ................................................................................................................................... 12 
2.2 
Secondary Objectives .............................................................................................................................. 13 
3.0 
PATIENT SELECTION (4/20/15) ............................................................................................................. 13 
3.1 
Conditions for Patient Eligibility (3/31/14) ................................................................................................ 13 
3.2 
Conditions for Patient Ineligibility (3/31/14) ............................................................................................. 14 
4.0 
PRETREATMENT EVALUATIONS/MANAGEMENT .............................................................................. 14 
4.1 
Required Evaluations/Management (3/31/14) ......................................................................................... 14 
4.2 
Highly Recommended Evaluations/Management ................................................................................... 14 
5.0 
REGISTRATION PROCEDURES (01-Feb-2019) ................................................................................... 14 
5.1 
Radiation-Specific Pre-Registration Requirements (3/31/14).................................................................. 15 
5.2 
Digital RT Data Submission to NRG Oncology Using TRIAD  (01-Feb-2019) ........................................ 16 
5.3 
Regulatory Pre-Registration Requirements (01-Feb-2019) ..................................................................... 16 
5.4 
Registration  (01-Feb-2019) .................................................................................................................... 19 
6.0 
RADIATION THERAPY (4/20/15) ............................................................................................................ 19 
6.1 
Dose Specifications (4/20/15) .................................................................................................................. 20 
6.2 
Technical Factors [Equipment, energies] ................................................................................................ 20 
6.3 
Localization, Simulation, and Immobilization ........................................................................................... 20 
6.4 
Treatment Planning/Target Volumes (12/17/13) ..................................................................................... 20 
6.5 
Critical Structures .................................................................................................................................... 21 
6.6 
Documentation Requirements (12/17/13) (3/31/14) ................................................................................ 21 
6.7 
Compliance Criteria (12/17/13) ................................................................................................................ 22 
6.8 
Treatment Interruption ............................................................................................................................. 22 
6.9 
R.T. Quality Assurance Reviews (12/17/13)............................................................................................ 22 
6.10 
Radiation Adverse Events ....................................................................................................................... 22 
    7.0     DRUG THERAPY (4/20/15) ..................................................................................................................... 23 
7.1 
Treatment (4/6/12) ................................................................................................................................... 23 
7.2 
Cisplatin (4/6/12) ...................................................................................................................................... 23 
7.3 
Cisplatin Dose Modifications (4/6/12) ...................................................................................................... 24 
7.4 
Mitomycin (4/6/12) ................................................................................................................................... 24 
7.5 
5FU (4/6/12) ............................................................................................................................................. 24 
7.6 
5FU Dose Modifications (4/6/12) ............................................................................................................. 24 
7.7 
Treatment Interruption (4/6/12) ................................................................................................................ 25 
7.8 
Modality Review (4/6/12) (3/31/14) .......................................................................................................... 25 
7.9 
Adverse Events  (01-Feb-2019) .............................................................................................................. 25 
7.10 
CTEP-AERS Adverse Event Reporting Requirements (3/31/14)(3/6/2015) ........................................... 26 
    8.0     SURGERY (4/20/15) ................................................................................................................................ 28 
8.1 
Pre-Chemoradiation Evaluation ............................................................................................................... 28 
8.2 
Post-Chemoradiation Endoscopic Response Evaluation ........................................................................ 28 
8.3 
Radical Cystectomy ................................................................................................................................. 28 
8.4 
Surveillance Cystoscopies in Complete Responding Patients ................................................................ 29 
8.5  
Surgical Quality Assurance Reviews ....................................................................................................... 29 
    9.0     OTHER THERAPY ................................................................................................................................... 29 
9.1 
Permitted Supportive Therapy (4/6/12) ................................................................................................... 29 
   10.0     TISSUE/SPECIMEN SUBMISSION (4/20/15) ......................................................................................... 29 
10.1 
Tissue/Specimen Submission ................................................................................................................. 29 
10.2 
Specimen Collection: Strongly Recommended (12/17/13) ...................................................................... 30 


5  
RTOG 0926; version date February 01, 2019 
 
 
10.3      Confidentiality/Storage (01-Feb-2019) .................................................................................................... 31 
    11.0      PATIENT ASSESSMENTS ..................................................................................................................... 31 
11.1 
Study Parameters: See Appendix I for a summary of assessments  ...................................................... 31 
11.2 
Evaluation Following Chemoradiotherapy ............................................................................................... 31 
11.3 
Measurement of Response ..................................................................................................................... 32 
11.4 
Criteria for Discontinuation of Protocol Treatment .................................................................................. 32 
   12.0      DATA COLLECTION  (01-Feb-2019) ..................................................................................................... 32 
12.1 
Summary of Data Submission (12/17/13)................................................................................................ 33 
12.2 
Summary of Dosimetry Digital Data Submission (Submit to TRIAD; see Section 5.0 for ....................... 33 
    13.0     STATISTICAL CONSIDERATIONS ......................................................................................................... 34 
13.1  
Study Endpoints ....................................................................................................................................... 34 
13.2 
Sample Size ............................................................................................................................................. 34 
13.3 
Accrual and Duration(3/6/2015) ............................................................................................................... 34 
13.4 
Analysis Plan ........................................................................................................................................... 34 
13.5 
Gender and Minorities ............................................................................................................................. 35 
    REFERENCES .................................................................................................................................................... 37 
    APPENDIX I: STUDY PARAMETER TABLE: Pre-Study Assessments (3/31/14) .............................................. 39 
    APPENDIX II ........................................................................................................................................................ 41 
    APPENDIX III(3/6/2015) ...................................................................................................................................... 42 
    APPENDIX IV ...................................................................................................................................................... 44 
    APPENDIX V(3/6/2015) ....................................................................................................................................... 44 
    APPENDIX VI (4/20/15) ....................................................................................................................................... 46 
 
 
 
 
 
 


6  
RTOG 0926; version date February 01, 2019 
 
 
NRG ONCOLOGY 
 
RTOG 0926 
 
A Phase II Protocol For Patients With Stage T1 Bladder Cancer To Evaluate Selective Bladder Preserving 
Treatment By Radiation Therapy Concurrent With Radiosensitizing Chemotherapy Following A Thorough 
Transurethral Surgical Re-Staging 
SCHEMA 
(3/31/14) 
 
Institutional TURBT 
for re-staging 
→ 
 
Full-dose Radiation* 
and 
Concurrent Chemotherapy**  → 
Cystoscopic Surveillance 
8-10 weeks after treatment; if 
negative, q 3 months for the 
1st year, q 4 months for year 2, 
q 6 months for years 3, 4, and 
5*** and then annually 
Stage T1 (high grade) 
*Total dose of 61.2 Gy in 
34 daily fractions 
 
**Cisplatin 3 days/week  
during Weeks 1, 3, and 5 
OR  
Mitomycin day 1 and 5-fluorouracil 
Weeks 1 and 4 
***For T1 and Tcis tumor 
recurrence after RTOG 0926 
treatment, recommend early 
salvage cystectomy. For Ta 
tumor recurrence, recommend 
either appropriate conservative 
treatment or cystectomy. 
 
See pre-registration requirements in Section 5.1. See details of radiation therapy and chemotherapy in Sections 
6.0 and 7.0. 
 
Patient Population:  (See Section 3.0 for Eligibility) (3/31/14) 
• 
Operable patients with non-muscle invading tumors and with at least one being a high grade Stage T1 
urothelial carcinoma for whom radical cystectomy is being considered as the next conventional step in 
therapy by standard urologic guidelines 
• 
AJCC Stages T1, NX or N0, M0, only transitional cell histology 
• 
Restaged by a urologist in the participating institution with an aggressive, visibly complete TURBT with 
muscularis propria in the specimen but with no evidence of its invasion by tumor 
• 
Failed standard treatment with, or is medically ineligible for, intravesical biological therapy or 
chemotherapy 
• 
No evidence of prostatic stromal invasion by tumor 
 
 
Required Sample Size: 37 
  


7  
RTOG 0926; version date February 01, 2019 
 
 
 
NRG Oncology Institution #   
 
RTOG 0926 
 
 
 
ELIGIBILITY CHECKLIST (4/20/15) 
Case #  
 
 
 
     (page 1 of 3) 
 
1.______(Y) Does the patient have pathologically proven non-muscle invading urothelial carcinoma of the bladder 
diagnosed within 105 days prior to registration? 
 
2.______(Y) Is the patient's initial non-muscle invading primary tumor or the recurrent non-muscle invading tumor 
a stage T1 high grade (either grade 2 or 3) urothelial carcinoma of the bladder? 
 
____(Y) If yes, is there evidence in the pathologic specimen of the recurrent tumor that there is no muscularis 
propria invasion by the tumor (that is, muscularis propria is in the specimen and not involved with tumor)? 
 
3.______(Y) Does the participating urologist judge that radical cystectomy is the next standard therapy for this 
patient per standard urologic guidelines? 
 
4______(Y/N) Has this patient either been judged unsuited for BCG therapy by the urologist or the patient, or 
failed initial treatment with TURBT + intravesical BCG therapy within 540 days (18 months) after this treatment?  
 
_____(Y) If no, has this patient been deemed medically ineligible for standard treatment for T1 bladder cancer (by 
further intravesical BCG therapy)? 
Please specify this reason:                                                                                                                                
(Either the urologist has judged the patient likely intolerant of BCG therapy due to his/her immuno competence, or 
the patient refuses this therapy.) 
 
5.______(N/Y) Has a radiologic lymph node evaluation been interpreted as positive? 
 
____(Y) If yes, has further evaluation been done by lymphadenectomy or needle biopsy to confirm no histological 
or cytological nodal metastases? 
 
6.______(Y) Has the patient undergone, a visibly complete transurethral resection of the present bladder tumor 
leaving an adequately functioning bladder? 
 
7.______(Y) Are the urologist, radiation oncologist and medical oncologist in joint agreement that the patient is 
able to tolerate systemic chemotherapy combined with radiation therapy and a radical cystectomy (if necessary)? 
 
8.______(Y) Has a history and physical examination been done within 60 days prior to registration? 
 
9.______(Y) Is the Zubrod performance status 0 or 1? 
 
10._____(Y) Is the patient 18 years of age or older? 
 
11._____(Y) Has a CBC with differential been done within 30 days prior to registration meeting the following 
parameters: WBC > 4,000; ANC > 1,800; platelets > 100,000 and hemoglobin > 10.0? 
 
12._____(Y) If the patient will be receiving cisplatin, is the serum creatinine < 1.5? 
 
13._____(Y) Is the serum bilirubin < 2.0? 
 
14._____(Y) Is the GFR > 25 ml/min? 
 
15._____(Y) If the patient will be receiving cisplatin, is the GFR ≥ 60 ml/min? 
 
16._____(N/Y) Is the patient a female of childbearing potential? 
 
17.____(Y) If yes, has a serum pregnancy test been done < 72 hours prior to registration? 


8  
RTOG 0926; version date February 01, 2019 
 
 
 
18._____(N) Is there evidence of tumor-related hydronephrosis? 


9  
RTOG 0926; version date February 01, 2019 
 
 
 
NRG Oncology Institution #   
 
RTOG 0926 
 
 
 
ELIGIBILITY CHECKLIST (3/31/14) 
Case #  
 
 
 
     (page 2 of 3) 
 
19._____(N) Is there evidence of distant metastases? 
 
20._____(N) Has the patient received systemic chemotherapy for bladder cancer? 
 
21._____(N) Does the patient have a prior invasive malignancy (except for non-melanomatous skin cancer; T1a 
prostate cancer or carcinoma of the uterine cervix) that has not been disease free for ≥ 5 year period or a 
urothelial carcinoma of the upper urinary tract stage pTa, pTis or pT1 that has been free of disease after 
treatment for more than a 2 year period? 
 
22._____(N) Is the patient currently receiving any drugs that have potential nephrotoxicity or ototoxicity (such as 
aminoglycoside)? 
 
23._____(N) Has the patient had any previous radiotherapy to the region of the study cancer that would result in 
overlap of radiation therapy fields? 
 
24._____(N) Does the patient have any severe, active co-morbidity such as: 1) unstable angina and /or 
congestive heart failure that required hospitalization within the last 6 months; 2) transmural myocardial infarction 
that occurred within the last 6 months; 3) acute bacterial or fungal infection requiring intravenous antibiotics at the 
time of registration; 4) chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring 
hospitalization or precluding any study therapy at the time of registration; 5) hepatic insufficiency resulting in 
clinical jaundice and/or coagulation defects or 6) acquired immune deficiency syndrome (AIDS) based upon the 
current CDC definition? 
 
25._____(Y;N/A) If the patient is of child-bearing potential (female) or is a sexually active male, are they 
willing/able to use medically acceptable forms of contraception? 
If N/A, please state why:______________________________________ 
 
26._____(N) Has the patient had a prior allergic reaction to the study drug (cisplatin, mitomycin, 5FU) used in this 
protocol? 
 
27.______(N) Does the patient have pathologically positive nodal disease (pN1;pN2; pN3)? 
 
28.______(N) Does the patient have T2, T3 or T4 disease? 
 
The following questions will be asked at Study Registration:  
 
3D CREDENTIALING IS REQUIRED PRIOR TO REGISTRATION 
 
 
         
1. 
Institutional person registering this case 
 
                  (Y) 2. 
Has the Eligibility Checklist been completed? 
 
                  (Y) 3. 
In the opinion of the investigator, is the patient eligible? 
 
 
         
4. 
Date Informed Consent signed 
 
 
         
5. 
Participant Initials 
 
 
         
6. 
Verifying Physician 
 
 
         
7. 
Patient’s ID Number 
 
 
         
8. 
Date of Birth 


10  
RTOG 0926; version date February 01, 2019 
 
 
NRG Oncology Institution #   
 
RTOG 0926 
 
 
 
ELIGIBILITY CHECKLIST (3/31/14) 
Case #  
 
 
 
     (page 3 of 3)  
 
 
 
         
9. 
Race 
 
 
         
10. 
Ethnicity 
 
 
         
11. 
Gender 
 
 
         
12. 
Country of Residence 
 
 
         
13. 
Patients’ Zip Code 
 
 
         
14. 
Method of Payment 
 
 
         
15. 
Any care at VA or military hospital? 
 
 
         
16. 
Calendar Base Date 
 
 
         
17. 
Randomization Date 
 
 
         
18. 
Medical oncologist 
 
              (N/Y) 19. 
Have you obtained the patient's consent for his or her tissue to be kept for use in 
research to learn about, prevent, treat, or cure cancer?  
 
              (N/Y) 20.  
Have you obtained the patient's consent for his or her blood to be kept for use in  
research to learn about, prevent, treat, or cure cancer?  
 
              (N/Y) 21. 
Have you obtained the patient's consent for his or her urine to be kept for use in research  
to learn about, prevent, treat, or cure cancer?  
 
              (N/Y) 22. 
Have you obtained the patient's consent for his or her tissue to be kept for use in  
research about other health problems (for example: causes of diabetes, Alzheimer's 
disease, and heart disease)?   
 
              (N/Y) 23. 
Have you obtained the patient's consent for his or her blood to be kept for use in  
research about other health problems (for example: diabetes, Alzheimer's disease, or 
heart disease).  
 
              (N/Y) 24. 
Have you obtained the patient's consent for his or her urine to be kept for use in  
research about other health problems (for example: causes of diabetes, Alzheimer's 
disease, and heart disease)?   
 
              (N/Y) 25. 
Have you obtained the patient's consent to allow someone from this institution to contact  
him or her in the future to take part in more research?  
 
 
 
 
The Eligibility Checklist must be completed in its entirety prior to web registration. The completed, signed, and 
dated checklist used at study entry must be retained in the patient’s study file and will be evaluated during an 
institutional NCI/NRG Oncology audit. 
 
Completed by  
 
 
 
 
 
Date 
 
 
 
 
 
 
 
 
 
 


11  
RTOG 0926; version date February 01, 2019 
 
 
1.0 INTRODUCTION 
1.1 
Background for Evaluating Trimodality Therapy in Patients with Aggressive Forms of Non-Muscle 
Invading Bladder Cancer Who Have Failed Other Conservative Treatments (3/31/14) 
Treating patients with muscle-invading bladder cancer (clinical stages T2-T4a, in X-N0, M0) with selective 
bladder preservation using trimodality therapy (transurethral resection [TURBT] plus concomitant 
chemotherapy and radiation therapy) with prompt cystectomy for recurrence has been established as a safe 
and effective alternative to immediate radical cystectomy in several RTOG protocols and in single institution 
reports.1 The treatment design that has evolved consists of as thorough a TURBT as is safely possible 
followed by irradiation to 64–65 Gy with concurrent sensitizing chemotherapy. Patients with a complete 
response are followed with surveillance cystoscopy; cystectomy is reserved for patients with recurrent 
disease.  Patients without a complete response undergo prompt cystectomy.    
 
The results over the last 3–4 decades using external beam therapy alone for patients with clinical stage 
T1 bladder cancer have been poor and this approach has been largely abandoned.  The Medical 
Research Council from the United Kingdom reported a multi-institutional randomized trial comparing 
external beam radiation therapy without concurrent chemotherapy to standard conservative approaches 
for the treatment of patients presenting with T1G3 tumors and confirmed no benefit from external beam 
therapy alone.2  The T1G3 subgroup of non-muscle invading bladder cancer is the most aggressive but 
makes up only 15% of the total incidence of patients presenting with non-muscle invading cancer.3  
TURBT alone has long been recognized as inadequate treatment with 48% of patients progressing to 
stage T2 or greater disease in just 3 years.4  The addition of BCG (bacillus Callamette-Guerin) 
immunotherapy after TURBT has been shown in a randomized trial to significantly improve the 10-year 
tumor progression-free rate from 37% to 62% and the 10-year disease-specific survival from 55% to 75%, 
when compared to TURBT alone.5  This combination now constitutes the current standard first-line 
therapy.3  The standard second-line treatment for patients who fail BCG therapy having had a stage T1 
tumor is radical cystectomy.3,6,7  This is because there is no very effective second-line bladder preserving 
treatment using additional intravesical agents in patients who develop a recurrence following BCG 
therapy.  Such therapies include BCG + interferon, mitomycin C, gemcitabine, adriamycin, docetaxel, 
apaziquone, and various combinations of these agents. The results of these intravesical therapies are 
generally poor and have short follow up.9-11 Because effective second-line bladder-sparing therapy using 
these intravesical agents is not well established, the standard treatment in this setting is radical 
cystectomy, as is recommended in the recent National Comprehensive Cancer Network (NCCN) 
Guidelines for Bladder Cancer.12   
  
However, there are recent indications that concurrent chemotherapy with radiation therapy, unlike 
radiation alone, may be very effective in eradicating high grade clinical stage T1 tumors.  This is based on 
results from Erlangen, Germany13 on 84 patients with T1G3 tumors using a trimodality bladder-sparing 
approach with concurrent chemotherapy and radiation.  A 10-year progression-free rate of the bladder 
tumor of 71% and a 10-year disease-specific survival rate of over 70% was reported.  These results in 
patients with T1G3 tumors are similar to the present standard bladder sparing approach using intravesical 
BCG in both preventing the progression of the primary tumor and in disease-specific survival (see 
reference 12, table 4).  This favorable result with trimodality therapy in T1G3 tumors makes sense since 
this approach has been shown to yield good results in patients presenting with muscle invading tumors of 
clinical stage T2.  RTOG protocols and single institution studies1,14 report a 70+% disease-specific 
survival rate at 5 years with less than 1/3 of these patients requiring a salvage radical cystectomy.  Thus, 
although there will always be the need in some patients for salvage cystectomy, treatment by this 
trimodality technique will likely prevent the need for radical cystectomies in many patients with non-
muscle invading bladder cancer who have failed BCG intravascular therapy having had high grade T1 
disease or high grade Ta disease.   
 
To our knowledge there are no reports as yet of the effectiveness of trimodality therapy as second-line 
selective bladder preserving treatment in patients with recurrent T1 bladder tumors following BCG 
treatment.  The Massachusetts General Hospital has reported a selective retrospective series of 18 
patients who had failed BCG therapy given for T1 bladder cancer who recurred with progression to a 
clinical stage T2 muscle-invading cancer. The median follow-up was 7.1 years. Ten of 18 patients have 
had no recurrence of any bladder tumor, muscle-invading or non-muscle invading. The freedom from 
cystectomy at 3 years was 94%. The actuarial 5-year disease-specific survival rate is 77%.15  Thus, the 
present protocol is designed to test the efficacy of chemotherapy-enhanced radiation therapy for the 


12  
RTOG 0926; version date February 01, 2019 
 
 
eradication of bladder cancers with aggressive forms of clinical stage T1 disease in whom radical 
cystectomy is, by standard urologic guidelines, the next step in therapy.    
 
Based on the above two Phase II reports with concurrent cisplatin and radiation in T1G3 or BCG-failures 
in bladder cancer, concurrent cisplatin has been selected as the radiation enhancing drug for this 
protocol. In patients who are not felt to be optimal candidates for cisplatin chemotherapy, mitomycin and 
5FU may be substituted as radiation sensitizing chemotherapy. To be eligible for this trial, all patients 
must be re-staged by a urologist in the participating institution with an aggressive, visibly complete 
TURBT with muscularis propria in the specimen but with no evidence of its invasion by tumor.  Thus, 
although there will always be the need in some patients for a salvage cystectomy, treatment by this 
technique will likely prevent the need for radical cystectomy in many patients—probably as many as 3 out 
of every 4—who have failed BCG therapy having initially had high grade T1 disease or who have failed 
BCG therapy for an initial high grade stage Ta tumor but who failed BCG with a high grade stage T1 
tumor.  If cystectomy could be safely avoided in 50–60% of such patients using a trimodality approach, 
this would be of considerable clinical importance.                                               
  
1.2 
Rationale for Evaluating Patient Tolerance for Whole Bladder Irradiation to 61.2 Gy with 
Concurrent Chemotherapy (4/6/12) 
Efstathiou, Bae, et al recently reported late pelvic toxicity following bladder-sparing therapy in patients 
with invasive bladder cancer in the analysis of RTOG protocols 8903, 9506, 9706, and 9906.16  Of 157 
patients enrolled in these four prospective RTOG protocols who underwent combined modality therapy 
and who are surviving two or more years from the start of their treatment with their bladder intact (median 
follow-up of 5.4 years), 7% experienced late grade 3 pelvic toxicity (5.7% GU and 9.1% GI).  Grade 3 GU 
toxicity persisted in only one of the nine patients with this toxicity.  There were no late grade 4 toxicities 
and no treatment related deaths.  Because the rate of significant late pelvic toxicity for patients 
completing combined modality therapy for invasive bladder cancer is low and likely will be for the 
proposed trial, the protocol differs slightly from methods used in the previous protocols with patients with 
usually unifocal but muscle invading transitional cell carcinoma of the bladder.  In these prior trials, the 
whole bladder dose was recommended to be at the 55 Gy level with the final 10-12 Gy boost being, if 
safely possible, only to the tumor bearing portion of the bladder.  Thus the present proposed regimen for 
the failed T1G3 patients in whom tumors may be multifocal includes radiating the whole bladder to doses 
of 61.2 Gy.  This probably will not result in more acute or late bladder toxicity. The Birmingham Hospital in 
England led a phase III trial evaluating patients with muscle-invading bladder cancer who received 
radiation treatment to the whole bladder compared to patients who received partial bladder radiation but 
with no concurrent chemotherapy.  Those patients assigned to partial bladder radiation were given a 
slightly higher dose.17  They reported no difference in late bladder toxicity (grade 2 or grade 3 toxicity 
using the WHO Toxicity Grading System).  The University of Michigan recently reported on their phase I 
trial of combined modality therapy with gemcitabine and radiation as a bladder preserving strategy (with 
5.6 years of median follow up) at the 2008 Genitourinary Symposium, sponsored by ASCO, ASTRO, and 
the SUO.18 Their treatment approach was similar to this present protocol in that treatment followed a 
maximum TURBT; the radiation doses and fields were very similar as well.  A small pelvic field was 
treated conformally to 40 Gy and the bladder only boost was treated for an additional 20 Gy—all in 2.0 Gy 
fractions for a total whole bladder dose of 60 Gy.  In this gemcitabine dose-seeking study there were no 
instances of late grade 3 GI or GU toxicity and the whole bladder radiation dose was certainly the 
biological equivalent of what we propose in this study (61.2 Gy in thirty-four 1.8 Gy daily fractions).  We 
will monitor late GU toxicity and be able to compare it to the results of our other trials.19    
  
1.3 
Biomarkers in Bladder Cancer(3/6/2015) 
A number of biomarkers have shown promise in predicting the outcome of bladder cancer patients.  In 
particular, her2/neu, EGFR1, p53, p21, pRb, p16 and bcl2.  These markers and others are under 
investigation through the NRG Oncology genitourinary translational research program using patients from 
an ongoing RTOG selective bladder preservation protocol.  These continued efforts are planned for the 
tissue from diagnostic/pretreatment TURBT and from cystectomy specimens, when salvage cystectomy is 
performed.   
 
2.0 OBJECTIVES 
2.1 
Primary Objectives 
To evaluate the rate of freedom from radical cystectomy at 3 years.   


13  
RTOG 0926; version date February 01, 2019 
 
 
  
 
 
2.2 
Secondary Objectives 
2.2.1 
To evaluate the rate of freedom from radical cystectomy at 5 years 
2.2.2 
To evaluate the rate of freedom from the development of distant disease progression at 3 and 5 years 
2.2.3 
Rate of freedom from progression of bladder tumor to stage T2 or greater at 3 and 5 years 
2.2.4 
To evaluate disease-specific survival and overall survival 
2.2.5 
To evaluate the incidence of acute and late pelvic toxicity 
2.2.6 
To evaluate the efficacy of this treatment approach in preventing the recurrence of any local bladder 
tumor 
2.2.7 
To evaluate the potential value of tumor histopathology plus molecular genetic, DNA content, and urine 
proteomics parameters as possible significant prognostic factors for tumor control with this treatment 
approach    
2.2.8 
To collect American Urological Association (AUA) symptom scores at baseline and at 3 years 
 
3.0 PATIENT SELECTION (4/20/15) 
NOTE: PER NCI GUIDELINES, EXCEPTIONS TO ELIGIBILITY ARE NOT PERMITTED  
For questions concerning eligibility, please contact the study data manager. 
3.1 
Conditions for Patient Eligibility (3/31/14) 
3.1.1 
Pathologically proven diagnosis of carcinoma of the bladder within 105 days prior to registration.  
• 
Operable patients whose initial tumor is a primary high grade urothelial carcinoma of the bladder 
exhibiting histologic evidence of invasion into the lamina propria (disease clinical stage T1) or a 
high grade stage Ta urothelial carcinoma without hydronephrosis; patients who have involvement 
of the prostatic urethra with urothelial carcinoma and have no evidence of stromal invasion of the 
prostate remain eligible.  If the patient’s initial tumor was a high grade stage Ta urothelial 
carcinoma then his/her recurrent tumor must be a high grade stage T1 urothelial carcinoma to be 
eligible.   
3.1.2 
Patients must have a high grade urothelial carcinoma stage Ta or T1 that has recurred within 540 days 
after completion of the initial treatment (TURBT and intravesical BCG immunotherapy) or on initial 
presentation  with a T1 high grade tumor, the participating urologist judged BCG therapy is 
contraindicated or unsuitable  because the patient  is found to be intolerant of BCG therapy or because 
this patient may be immuno-compromised in ways other than that mentioned in Section 3.2.8 or because 
the patient refuses BCG therapy. 
3.1.3 
With the presentations as described in Section 3.1.2, the participating urologist judges that the standard 
next therapy, based on present urologic guidelines for this patient, is radical cystectomy. 
3.1.4 
If radiologic evaluation of a lymph node is interpreted as “positive”, this must be evaluated further either 
by lymphadenectomy or by percutaneous needle biopsy. Patients with histologically or cytologically 
confirmed node metastases will not be eligible.   
3.1.5 
Patients must have an adequately functioning bladder as judged by the participating urologist and 
radiation oncologist and have undergone a re-staging TURBT by the participating urologist that showed 
(or was present in the outside pathology specimen) a high grade stage Ta or T1 tumor with uninvolved 
muscularis propria in the specimen and, if on prostatic urethral biopsy mucosal carcinoma is present, 
there is no evidence on biopsy in the prostatic stroma of tumor invasion. 
3.1.6 
Patient must be considered able to tolerate systemic chemotherapy combined with pelvic radiation 
therapy, and a radical cystectomy (if necessary) by the joint agreement of the participating urologist, 
radiation oncologist, and medical oncologist. 
3.1.7 
Appropriate stage for protocol entry, based upon the following minimum diagnostic workup within 60 days 
prior to registration: 
• 
History/physical examination including weight, performance data, body surface area 
3.1.8  
Zubrod Performance Status ≤ 1 
3.1.9 
Age ≥ 18 
3.1.10 CBC/differential obtained no more than 30 days prior to registration on study, with adequate bone marrow 
function defined as follows: 
• 
WBC ≥ 4,000/ml 
• 
Absolute neutrophil count (ANC) ≥ 1,800 cells/mm3  
• 
Platelets ≥ 100,000 cells/mm3  
• 
Hemoglobin ≥ 10.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 10.0 
g/dl is acceptable.) 


14  
RTOG 0926; version date February 01, 2019 
 
 
3.1.11 If the patient is to be treated with cisplatin, the serum creatinine should be ≤ 1.5 mg%; serum bilirubin of ≤ 
2.0 mg% 
3.1.12 GFR > 25 ml/min [For patients receiving cisplatin, GFR ≥ 60 ml/min] 
3.1.13 Serum pregnancy test for female patients of childbearing potential, ≤ 72 hours prior to study entry; women 
of childbearing potential and male participants must practice adequate contraception. 
3.1.14 Patient must be able to provide study-specific informed consent prior to study entry. 
 
3.2 
Conditions for Patient Ineligibility (3/31/14) 
3.2.1 
Evidence of tumor-related hydronephrosis 
3.2.2 
Evidence of distant metastases or histologically or cytologically proven lymph node metastases 
3.2.3 
Prior systemic chemotherapy for bladder cancer; prior chemotherapy for a different cancer is allowable  
3.2.4 
A prior or concurrent malignancy of any other site or histology unless the patient has been disease-free 
for ≥ 5 years except for non-melanoma skin cancer and/or stage T1a prostate cancer or carcinoma in situ 
of the uterine cervix or a urothelial carcinoma of the upper urinary tract stage pTa, pTis or pT1 that has 
not been free of disease after treatment for more than a 2 year period 
3.2.5 
Patients with pN+ or > T1 disease or who have not had a visibly complete TURBT 
3.2.6 
Patients receiving any drugs that have potential nephrotoxicity or ototoxicity (such as an aminoglycoside) 
3.2.7 
Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields 
3.2.8 
Severe, active co-morbidity, defined as follows: 
• 
Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months; 
• 
Transmural myocardial infarction within the last 6 months; 
• 
Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; 
• 
Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring 
hospitalization or precluding study therapy at the time of registration; 
• 
Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that 
laboratory tests for liver function and coagulation parameters are not required for entry into this 
protocol. 
• 
Acquired Immune Deficiency Syndrome (AIDS) based upon the current CDC definition; note, 
however, that HIV testing is not required for entry into this protocol. The need to exclude patients 
with AIDS from this protocol is necessary because the treatments involved in this protocol may be 
significantly immunosuppressive.  Protocol-specific requirements may also exclude immuno-
compromised patients. 
3.2.9 
Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to 
use medically acceptable forms of contraception; this exclusion is necessary because the treatment 
involved in this study may be significantly teratogenic.  
3.2.10 Prior allergic reaction to the study drugs (cisplatin, mitomycin, 5FU) involved in this protocol  
 
4.0 
PRETREATMENT EVALUATIONS/MANAGEMENT 
Note: This section lists baseline evaluations needed before the initiation of protocol treatment that 
do not affect eligibility.    
4.1 
Required Evaluations/Management (3/31/14) 
4.1.1 
Cystoscopic evaluation by a participating urologic surgeon will include a visibly complete transurethral 
resection of the bladder tumor (TURBT), bimanual examination under anesthesia, and prostatic urethra 
biopsies (see Section 8.1.5), as well as a biopsy of the base of the resected tumor site.  Patients referred 
from an outside hospital will be re-resected by the participating urologist.  
4.1.2     Radiologic evaluation, including chest x-ray, bone scan (as applicable), abdominal and pelvic CT scans, 
and an IVP if indicated, no more than 60 days prior to start of treatment 
4.1.3 
Alkaline phosphatase, SGOT, LDH, BUN, magnesium and calcium levels 
 
4.2 
Highly Recommended Evaluations/Management 
4.2.1 
AUA Symptom score at baseline before beginning concurrent chemotherapy and radiation 
 
5.0 
REGISTRATION PROCEDURES (01-Feb-2019) 
Access requirements for OPEN and TRIAD 
Site staff will need to be registered with CTEP and have a valid and active CTEP Identity and Access 
Management (IAM) account. This is the same account (user id and password) used for the CTSU 
members' web site. To obtain an active CTEP-IAM account, go to https://eapps-ctep.nci.nih.gov/iam. 
 


15  
RTOG 0926; version date February 01, 2019 
 
 
Food and Drug Administration (FDA) regulations and National Cancer Institute (NCI) policy require all 
individuals contributing to NCI-sponsored trials to register and to renew their registration annually.  To 
register, all individuals must obtain a Cancer Therapy Evaluation Program (CTEP) Identity and Access 
Management (IAM) account (https://ctepcore.nci.nih.gov/iam).  In addition, persons with a registration 
type of Investigator (IVR), Non-Physician Investigator (NPIVR), or Associate Plus (AP) (i.e., clinical 
site staff requiring write access to OPEN, RAVE, or TRIAD or acting as a primary site contact) must 
complete their annual registration using CTEP’s web-based Registration and Credential Repository 
(RCR) (https://ctepcore.nci.nih.gov/rcr).  Documentation requirements per registration type are 
outlined in the table below. 
 
Documentation Required 
IVR 
NPIVR 
AP 
A 
FDA Form 1572 
 
 
Financial Disclosure Form 
 
 
 
NCI Biosketch (education, training, employment, 
license, and certification) 
 
 
 
HSP/GCP training 
 
 
 
Agent Shipment Form (if applicable) 
 
CV (optional) 
 
 
 
 
An active CTEP-IAM user account and appropriate RCR registration is required to access all CTEP 
and CTSU (Cancer Trials Support Unit) websites and applications.  In addition, IVRs and NPIVRs 
must list all clinical practice sites and IRBs covering their practice sites on the FDA Form 1572 in 
RCR to allow the following: 
• 
Added to a site roster 
• 
Assigned the treating, credit, consenting, or drug shipment (IVR only) tasks in OPEN 
• 
Act as the site-protocol PI on the IRB approval 
 
Additional information can be found on the CTEP website.  For questions, please contact the RCR Help 
Desk by email at < RCRHelpDesk@nih.gov 
 
5.1 
Radiation-Specific Pre-Registration Requirements (3/31/14) 
Knowledge Assessment 
There is a required knowledge assessment for this protocol that is in addition to the Facility 
Questionnaire and the credentialing requirements. This knowledge assessment must be 
successfully completed prior to the enrollment of the first patient.  Details for the knowledge 
assessment can be found on the Imaging and Radiation Oncology Core (IROC) Houston QA 
Center [formerly the Radiological Physics Center (RPC)] website at 
http://irochouston.mdanderson.org . 
 


16  
RTOG 0926; version date February 01, 2019 
 
 
The RT treatment modality is 3DCRT (see Section 6.0). All sites must be 3DCRT credentialed.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
5.2 
Digital RT Data Submission to NRG Oncology Using TRIAD  (01-Feb-2019) 
TRIAD, the American College of Radiology’s (ACR) image exchange application, will be used for 
dosimetry digital treatment data on RTOG 0926. TRIAD provides sites participating in NRG 
Oncology clinical trials a secure method to transmit DICOM RT and other objects. TRIAD 
anonymizes and validates the images as they are transferred. 
 
TRIAD Access Requirements: 
• 
Site physics staff who will submit images through TRIAD will need to be registered with the 
Cancer Therapy Evaluation Program (CTEP) and have a valid and active CTEP Identity and 
Access Management (IAM) account, and be registered as an AP, NPIVR or IVR.  Please refer to 
the CTEP Registration Procedures section for instructions on how to request a CTEP-IAM 
account and complete registration in RCR. 
• 
To submit images, the site physics user must be on the site’s affiliated rosters and be assigned 
the 'TRIAD site user' role on the CTSU roster.  Users should contact the site’s CTSU 
Administrator or Data Administrator to request assignment of the TRIAD site user role.  RAs are 
able to submit standard of care imaging through the same method. 
 
TRIAD Installations: 
When a user applies for a CTEP-IAM account with proper user role, he/she will need to 
have the TRIAD application installed on his/her workstation to be able to submit images. 
TRIAD installation documentation can be found on the NRG Oncology/RTOG website Core 
Lab tab.    
 
This process can be done in parallel to obtaining your CTEP-IAM account username and 
password. 
 
If you have any questions regarding this information, please send an e-mail to the TRIAD Support 
mailbox at TRIAD-Support@acr.org. 
 
5.3 
Regulatory Pre-Registration Requirements (01-Feb-2019) 
5.3.1 
This study is not on the NCI Cancer Trials Support Unit (CTSU) Menu 
 
 IRB Approval:   
RT  
Credentialing 
Requirements 
 
Web Link for Procedures and Instructions: http://irochouston.mdanderson.org 
 
Treatment 
Modality: 3DCRT 
 
Key Information 
 
Facility 
Questionnaire 
X 
Update your online electronic Facility Questionnaire via the 
web address above. 
 
Credentialing 
Status Inquiry 
Form 
X 
Complete this form on the IROC Houston website above to 
determine if your site has met all of the requirements. This will 
be completed in place of updating the previous Facility 
Questionnaire. When the requirements are met the site and 
NRG Oncology (NRG) will be notified. NRG will then update 
the RSS database. 
 
Knowledge 
Assessment 
X 
The Knowledge Assessment Form will be available on the 
IROC website at  http://irochouston.mdanderson.org 
 


17  
RTOG 0926; version date February 01, 2019 
 
 
 
Each 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 be 
approved to enroll patients.  Assignment of site registration status in the CTSU Regulatory Support 
System (RSS) uses extensive data to make a determination of whether a site has fulfilled all regulatory 
criteria including but not limited to the following: 
• 
An active Federal Wide Assurance (FWA) number 
• 
An active roster affiliation with the Lead Network or a participating organization 
• 
A valid IRB approval 
• 
Compliance with all protocol specific requirements. 
 
In addition, the site-protocol Principal Investigator (PI) must meet the following criteria: 
• 
Active registration status 
• 
The IRB number of the site IRB of record listed on their Form FDA 1572 
• 
An active status on a participating roster at the registering site. 
 
Sites participating on the NCI CIRB initiative that are approved by the CIRB for this study are not required 
to submit IRB approval documentation to the CTSU Regulatory Office. For sites using the CIRB, IRB 
approval information is received from the CIRB and applied to the RSS in an automated process. 
Signatory Institutions must submit a Study Specific Worksheet for Local Context (SSW) to the CIRB via 
IRB Manager to indicate their intent to open the study locally.  The CIRB’s approval of the SSW is then 
communicated to the CTSU Regulatory Office.  In order for the SSW approval to be processed, the 
Signatory Institution must inform the CTSU which CIRB-approved institutions aligned with the Signatory 
Institution are participating in the study. 
 
Downloading Site Registration Documents:   
 
Site registration forms may be downloaded from the [NCI RTOG-0926] protocol page located on the 
CTSU members’ website.  Add if a restricted access protocol: Permission to view and download this 
protocol and its supporting documents is restricted and is based on person and site roster assignment 
housed in the CTSU RSS. 
 
Go to https://www.ctsu.org and log in to the members’ area using your CTEP-IAM username and 
password 
 
Click on the Protocols tab in the upper left of your screen 
 
Either enter the protocol # in the search field at the top of the protocol tree, or 
 
Click on the By Lead Organization folder to expand 
 
Click on the (state organization type e.g. P2C, CITN, NCTN Group name) link to expand, then 
select trial protocol #[RTOG-0926] 
 
Click on LPO Documents, select the Site Registration documents link, and download and 
complete the forms provided.   
   
 
Requirements For RTOG-0926 Site Registration: 
 
 
     IRB approval (For sites not participating via the NCI CIRB; local IRB documentation, an IRB-signed CTSU 
IRB Certification Form, Protocol of Human Subjects Assurance Identification/IRB Certification/Declaration 
of Exemption Form, or combination is accepted ) 
 
. 
 


18  
RTOG 0926; version date February 01, 2019 
 
 
Submitting Regulatory Documents:  
 
Submit required forms and documents to the CTSU Regulatory Office via the Regulatory Submission 
Portal, where they will be entered and tracked in the CTSU RSS.  
 
Regulatory Submission Portal: www.ctsu.org  (members’ area)  Regulatory Tab Regulatory 
Submission  
When applicable, original documents should be mailed to: 
CTSU Regulatory Office 
      1818 Market Street, Suite 3000 
      Philadelphia, PA 19103 
 
Institutions with patients waiting that are unable to use the Portal should alert the CTSU Regulatory Office 
immediately at 1-866-651-2878 in order to receive further instruction and support. 
) 
 
Checking Your Site’s Registration Status: 
 
You can verify your site registration status on the members’ section of the CTSU website.   
 
 Go to https://www.ctsu.org and log in to the members’ area using your CTEP-IAM username and 
password 
 Click on the Regulatory tab  
 Click on the Site Registration tab 
 Enter your 5-character CTEP Institution Code and click on Go 
 
Note: The status given only reflects compliance with IRB documentation and institutional compliance with 
protocol-specific requirements outlined by the Lead Network. It does not reflect compliance with protocol 
requirements for individuals participating on the protocol or the enrolling investigator’s status with the NCI 
or their affiliated networks. 
 
5.3.2 
In addition to the requirements noted above, ALL institutions must fax copies of the documentation 
below to the CTSU Regulatory Office (215-569-0206); study-related regulatory documentation also may 
be e-mailed to the CTSU at CTSURegulatory@ctsu.coccg.org. This must be done prior to registration of 
the institution’s first case: 
• 
IRB/REB approval letter; 
• 
IRB/REB approved consent (English and native language versions*) 
*Note: Institutions must provide certification/verification of consent translation to NRG Oncology (See 
“Non-English Speaking Canadian and Non-North American Institutions” below) 
• 
IRB/REB assurance number renewal information as appropriate 
 
Non-English Speaking Canadian and Non-North American Institutions 
Translation of documents is critical. The institution is responsible for all translation costs. All regulatory 
documents, including the IRB/REB approved consent, must be provided in English and in the native 
language. Certification of the translation is optimal but due to the prohibitive costs involved NRG 
Oncology will accept, at a minimum, a verified translation. A verified translation consists of the actual REB 
approved consent document in English and in the native language, along with a cover letter on 
organizational/letterhead stationery that includes the professional title, credentials, and signature of the 
translator as well as signed documentation of the review and verification of the translation by a neutral 
third party. The professional title and credentials of the neutral third party translator must be specified as 
well. 
5.3.3 
Pre-Registration Requirements FOR CANADIAN INSTITUTIONS 
 
Prior to clinical trial commencement, Canadian institutions must complete and fax (215-569-0206) or e-
mail (CTSURegulatory@ctsu.coccg.org) the following forms to the CTSU Regulatory Office: 
• 
Health Canada’s Therapeutic Products Directorates’ Clinical Trial Site Information Form,  
• 
Qualified Investigator Undertaking Form, and  
• 
Research Ethics Board Attestation Form.  
5.3.4 
Pre-Registration Requirements FOR NON-CANADIAN INTERNATIONAL INSTITUTIONS 


19  
RTOG 0926; version date February 01, 2019 
 
 
 
For institutions that do not have an approved LOI for this protocol: 
International sites must submit an LOI to NRG Oncology to receive approval to participate in this trial. For 
more details see link below: http://www.rtog.org/Researchers/InternationalMembers/LetterofIntent.aspx .  
For institutions that have an approved LOI for this protocol: 
 
All requirements indicated in your LOI Approval Notification must be fulfilled prior to enrolling patients to 
this study. 
 
5.4 
Registration  (01-Feb-2019) 
5.4.1  
OPEN Registration Instructions 
Patient registration can occur only after evaluation for eligibility is complete, eligibility criteria have been 
met, and the study site is listed as ‘approved’ in the CTSU RSS.  Patients must have signed and dated all 
applicable consents and authorization forms.   
 
Patient enrollment will be facilitated using the Oncology Patient Enrollment Network (OPEN).  OPEN is a 
web-based registration system available on a 24/7 basis.  To access OPEN, the site user must have an 
active CTEP-IAM account (check at < https://ctepcore.nci.nih.gov/iam >) and a 'Registrar' role on either 
the LPO or participating organization roster.  Registrars must hold a minimum of an AP registration type.  
. 
 
All site staff will use OPEN to enroll patients to this study.  It is integrated with the CTSU Enterprise 
System for regulatory and roster data.  OPEN can be accessed at https://open.ctsu.org or from the OPEN 
tab on the CTSU members’ side of the website at https://www.ctsu.org.  To assign an IVR or NPIVR as 
the treating, crediting, consenting, drug shipment (IVR only), or investigator receiving a transfer in OPEN, 
the IVR or NPIVR must list on their Form FDA 1572 in RCR the IRB number used on the site’s IRB 
approval. 
 
 
Prior to accessing OPEN site staff should verify the following: 
• 
All eligibility criteria have been met within the protocol stated timeframes. Site staff should use 
the registration forms provided on the group or CTSU web site as a tool to verify eligibility. 
• 
All patients have signed an appropriate consent form and HIPPA authorization form (if 
applicable).  
 
Access requirements for OPEN: 
• 
See Section 5.0 for obtaining a CTEP-IAM account.  
• 
To perform registrations, the site user must have been assigned the 'Registrar' role on the 
relevant Group or CTSU roster. Site and/or Data Administrators can manage CTSU roster 
roles via the new Site Roles maintenance feature under RSS on the CTSU members' web 
site. This will allow them to assign staff the "Registrar" role. 
 
The OPEN system will provide the site with a printable confirmation of registration and treatment 
information.  Please print this confirmation for your records.  
 
Further instructional information is provided on the CTSU members' web site OPEN tab or within the 
OPEN URL. For any additional questions contact the CTSU Help Desk at 1-888-823-5923 or 
ctsucontact@westat.com.  
 
In the event that the OPEN system is not accessible, participating sites can contact NRG Oncology web 
support for assistance with web registration: websupport@acr.org or call the Registration Desk at (215) 
574-3191, Monday through Friday, 8:30 a.m. to 5:00 p.m. ET. The registrar will ask the site to fax in the 
eligibility checklist and will need the registering individual’s e-mail address and/or return fax number. This 
information is required to assure that mechanisms usually triggered by the OPEN web registration system 
(e.g. drug shipment and confirmation of registration) will occur.   
  
 
6.0 
RADIATION THERAPY (4/20/15) 
This trial will not utilize the services of the ITC for dosimetry digital treatment data submission. 
PRIOR TO ENROLLING PATIENTS, please see Section 5.2 for information on installing TRIAD for 
submission of digital RT data. 


20  
RTOG 0926; version date February 01, 2019 
 
 
 
Note: Intensity Modulated RT (IMRT) Is Not Allowed 
 
Protocol treatment must begin within 15 weeks following transurethral resection.  Ideally, 
treatment should begin on a Monday, the chemotherapy to precede the daily radiation therapy during the  
first three treatments of weeks 1, 3, and 5.  Radiation treatment times must be recorded on the daily  
treatment record.   
 
Note:  Because the fields may be complicated for this study, it is recommended that the treating physician 
contact the Study Co-Principal Investigator, Dr. William Shipley (617-726-8146), to discuss fields prior to 
designing the CT simulated treatment plan. 
 
6.1 
Dose Specifications (4/20/15) 
All patients will receive 34 daily fractions (about 7 weeks) of radiation therapy 5 days a week.  Radiation 
therapy will be started within 15 weeks following the TURBT and begin on a Monday, Tuesday, or 
Wednesday.  Radiation therapy will be continuous, without a plan break for tumor assessment during 
treatment, as has been done in most of the prior RTOG bladder preservation protocols. The overall 
schema is for small field pelvic irradiation given by 3D conformal irradiation to the entire bladder and 
prostatic urethra (in men) and the lymph nodal pelvic regions of the internal iliac, the external iliac, and 
the obturator lymph nodes.  All these structures constitute the CTVCTV_4140 (see field borders in Appendix 
IV). The treatment will be given in 23 fractions at 1.8 Gy per daily fraction (5 days per week) to a dose of 
41.4 Gy, followed by reduction in field size to include the whole bladder and any possible or suggested 
areas of tumor extension (CTV_6120) using 1.8 daily fractions for 11 fractions for a total bladder boost dose 
(PTV_6120) of 19.8 Gy.  This will give a total dose to the gross bladder volume of 61.2 Gy over 
approximately 7 weeks. Heterogeneity corrections must be used. 
  
6.2 
Technical Factors [Equipment, energies] 
The radiation treatment should be with a high energy linear accelerator with photon energies ≥6 MV, 
typically using a four field box for the initial small pelvic fields and for the boost for the whole bladder 
volume, but there may be alternative field arrangements depending on specific characteristics of the 
individual patient (e.g., a patient with a metal total hip replacement). 
 
6.3 
Localization, Simulation, and Immobilization 
3D conformal radiotherapy will be used.  The patient will be positioned supine.  A leg immobilizer or 
cradle is recommended.  A planning CT scan of the pelvis will be obtained.  The patient must void to 
empty the bladder immediately prior to simulation.  The bladder is then catheterized to check on the size 
of a possible post void residual.  Twenty to 30 ml of dilute contrast and air may be introduced in the 
bladder but the bladder should not contain more liquid than that because it is desirable to treat the patient 
with their bladder empty such that the day-to-day mobility of the bladder will be minimized.  Contrast in 
the rectum usually is not necessary but a rectal tube without contrast may be helpful.  The rectum should 
be as empty as possible for simulation; an enema should be given prior to simulation to accomplish this.  
  
6.4 
Treatment Planning/Target Volumes (12/17/13) 
6.4.1 
Small Pelvic Fields 
These fields should encompass the entire bladder, prostate and prostatic urethra (in men), and the 
regional pelvic lymph nodes (See Appendix IV). All of these structures constitute the CTV_4140.  A 
conformal four field box arrangement should be used (the pelvic lymph nodes do not need to be 
contoured on the submitted 3D plan). The field margins in the inferior and superior dimensions should 
extend 1 cm below the lower pole of the obturator foramen to the mid-sacrum (the anterior aspect of the 
S1-S2 junction). Laterally, the anterior and posterior opposed fields will extend at least 1.5 cm beyond the 
widest point of the bony margin of the pelvis. For the parallel opposed lateral fields, the field edges will 
extend 3.0 cm posterior to the CTV_6120  and will extend 1 cm anterior to the most anterior point of the 
symphysis pubis or 1.5 cm anterior to the anterior tip of the bladder, whichever is the most anterior.  
Blocking should also be used on the anterio-posterior opposed fields to shield the medial border of the 
femoral heads. Blocking will also be employed on the lateral opposed fields inferiorly to shield the soft 
tissue anterior to the pubic symphysis and to block the anal canal posteriorly.  Superiorly, the lateral fields 
may include blocks anteriorly to exclude the small bowel and the anterior rectus fascia which lay anterior 
to the external iliac lymph node chain.   


21  
RTOG 0926; version date February 01, 2019 
 
 
 
The field weighting and use of beam modifiers should be chosen to assure that the maximum dose to the 
femoral heads is no more than 45 Gy.   
 
Anatomic variations in the bladder may necessitate modifications of the CTV_6120 and therefore the 
CTV_4140, such as a bladder cystocele protruding inferiorly or a bladder diverticulum or, rarely, a very 
significant post-void residual. Also, variations in the regional pelvic lymph nodes may necessitate 
modifications of the field borders for the small pelvic fields.  For any of these anatomic variations, the 
variation should be encompassed within the defined CTV_6120 and/or CTV_4140, as required. For such 
cases, the field edges should be adjusted to extend at least 2 cm beyond the modified CTV_4140.   
 
6.4.2 
Whole Bladder Field(2/25/2014) 
The CTV_6120 includes any gross tumor volume (GTV), the entire bladder volume, and the entire bladder 
wall thickness. The PTV_6120 consists of a margin 0.5 cm around the CTV_6120 edges except superiorly 
where the extension is 1.5 cm. The PTV_6120 may be treated by a four field box approach or by only 
parallel opposed lateral fields. Field corner shaping is employed using MLCs. 
 
The following table summarizes the naming of targets and critical structures for submission of data to 
RTOG. Note: Structures must be labeled as listed in the table below, and digital RT data submission of all 
of these structures is required. Resubmission of data may be required if labeling of structures does not 
conform to the standard DICOM name listed. 
 
 
RTOG 0926 
Standard Name 
Description 
CTV_4140 
Pelvic Target 
CTV_6120 
Whole Bladder Target 
PTV_6120 
0.5 cm expansion 
GTV 
Gross Tumor Volume 
External 
External patient contour 
Femur_L 
Left Femur 
Femur_R 
Right Femur 
Femurs 
Both femurs 
Rectum 
Rectum 
 
6.5 
Critical Structures 
Femoral and rectal structure doses must be assessed from DVHs calculated for composite (summed) 
treatment plans (Pelvis + whole bladder plans). The maximum dose to the femoral heads should be less 
than 45 Gy. Fifty percent of the rectum volume should receive less than 55 Gy (V55Gy <  50%). The rectum 
volume is defined on CT from the anus (at the level of the ischial tuberosities) for a length of 15 cm or to 
the rectosigmoid flexure.  
 
6.6 
Documentation Requirements (12/17/13) (3/31/14) 
6.6.1 
Within 7 working days of the initiation of treatment, the CT treatment plan must be submitted digitally to 
TRIAD (see Section 12.2). 


22  
RTOG 0926; version date February 01, 2019 
 
 
6.6.2 
Within 7 working days of the initiation of treatment, digitally reconstructed radiographs and initial 
approved small pelvis portal images of each treatment field in JPEG format must be submitted digitally to 
TRIAD (see Section 12.2).  
 
6.7 
Compliance Criteria (12/17/13) 
6.7.1 
Field Borders/Volumes 
Per Protocol:  Refer to Section 6.4. 
Variation Acceptable:  Actual field borders and/or PTVs vary within 1-2 cm from those stated in Section 
6.4 and include the target structures described above. 
Deviation Unacceptable:  Actual field borders and/or PTVs transect a target structure or deviate more 
than 2 cm beyond the borders stated in Section 6.4. 
6.7.2 
Specified Radiation Dose (Critical structures) 
Per Protocol: Refer to Section 6.5. 
Variation Acceptable: Maximum dose to the critical structure is between 0 and 10% higher than the 
specified protocol dose (See Section 6.5).    
Deviation Unacceptable: Maximum dose to the critical structure is greater than 10% higher than the 
specified protocol dose (See Section 6.5).   
6.7.3 
Minimum Isodose Coverage (Applies to CTV_4140  and PTV_6120 independently) 
Generally, the minimum dose to any target should be 95% of the prescription dose to that target.  To 
address the single pixel calculation anomalies, the D99% is used as the dose specifier.   
Per Protocol:  D99% > 95%.  Dose covering 99% of the volume of any target volume is no less than 95% 
of the prescribed dose.   
Variation Acceptable:  D99% < 95% but D99% > 90%.  Dose covering 99% of the volume of any target 
volume is no less than 90% of the prescribed dose. 
Deviation Unacceptable:  D99% < 90%.  Target structures coverage falls below 90% of the prescribed 
dose.  
6.7.4 
Maximum Dose (Applies to each target independently) 
Generally, the maximum dose to any target should be less than 107% of that target’s prescribed dose. 
Per Protocol:  V107% < 0.12 cc.  Less than 0.12 cc of the target receives a dose exceeding 107% of the 
prescribed dose.  
Variation Acceptable:  V107% > 0.12 cc but this dose does not exceed 110% of this dose.  
Deviation Unacceptable:  The maximum dose to the 0.12 cc volume does exceed 110% of the 
prescribed dose.   
6.7.5 
Elapsed Days 
Per Protocol:  No more than 7 break days 
Variation Acceptable:  8-14 break days 
Deviation Unacceptable:  15 or more break days 
 
6.8 
Treatment Interruption  
For a grade 3 acute colitis, cystitis, or any other grade 3 infield (radiation-related) toxicity during any 
treatment week, treatment (both radiation and chemotherapy) should be delayed until the toxicity 
subsides to the grade 2 level.  If the delay is greater than 3 weeks, then the patient should be considered 
intolerant of protocol therapy and appropriate off-protocol therapy given. 
 
6.9 
R.T. Quality Assurance Reviews (12/17/13) 
The Radiation Oncology Co-Chair, William Shipley, MD, will perform RT Quality Assurance Reviews after 
complete data for the first 20 cases enrolled has been received at IROC Philadelphia.  Dr. Shipley will 
perform the next review after complete data for the next 10 cases enrolled has been received at IROC 
Philadelphia. The final cases will be reviewed within 3 months after this study has reached the target 
accrual or as soon as complete data for all cases enrolled has been received at IROC Philadelphia, 
whichever occurs first. These reviews will be ongoing. 
   
6.10 
Radiation Adverse Events  
See Section 7.9 for additional Adverse Events information and Section 7.10 for Adverse Event Reporting 
Guidelines. 
●  Genitourinary: Frequency of urination, nocturia, acute or chronic bleeding from the bladder 
mucosal surface and ureteral obstruction 


23  
RTOG 0926; version date February 01, 2019 
 
 
●   Gastrointestinal: Rectal irritation, bowel obstruction or bleeding, rectal ulcers, hematochezia, 
fistula formation, nausea and/or vomiting 
●   Dermatologic: Erythema, loss of pubic hair which could be permanent 
●   Gynecological: Vaginal bleeding, fistula formation 
●   Other: Fatigue 
 
7.0  
DRUG THERAPY (4/20/15) 
 
Protocol treatment must begin within 15 weeks after transurethral resection. 
 
7.1 
Treatment (4/6/12) 
7.1.1 
Agents 
Two radiosensitizing chemotherapy regimens will be permitted for this study:  either cisplatin 
alone OR combination of mitomycin and 5FU. The choice may be made by treating physicians 
based on their medical discretion for platinum suitability. However, patients with GFR < 60 ml/min 
MAY NOT be treated with cisplatin. 
7.1.2 
Dose Definition 
Body surface area calculations will be based on actual or ideal body weight as per institutional policy.    
7.1.3 
Duration of Treatment  
Radiation and chemotherapy should both be held together. If any doses of chemotherapy are held or 
missed, they should not be made up.  
 
7.2 
Cisplatin (4/6/12) 
Refer to package insert for additional information. 
 
7.2.1 
Technique of Administration 
Cisplatin (15 mg/m2) will be administered as a 60-minute infusion on days 1, 2, 3, 15, 16, 17, 29, 30, and 
31 over 6 to 8 weeks. Pre-cisplatin hydration: On the days of cisplatin administration patients are 
instructed to increase their fluid intake to at least six 8-ounce glasses of water (or other fluids) over the 12 
hours prior to i.v. hydration preceding chemotherapy. Pre-cisplatin hydration should consist of 500 cc/hr 
of NS and should continue at that rate until a urinary output of ≥ 100 cc/hr is achieved. Post-cisplatin 
hydration: The post-cisplatin hydration i.v. hydration should consist of NS 500 cc in one hour. 
• 
Anti-emetic regimens, which may include ondansetron, granisetron, metroclopramide, lorazepam, 
dexamethasone, diphenhyramine hydrochloride and/or prochlorperazine, are recommended 
before and after cisplatin administration. 
7.2.2 
Dose Formulation 
Cisplatin is available as 10 mg and 50 mg vials of dry powder which are reconstituted with 10 ml and 50 
ml of sterile water for Injection USP, respectively. Cisplatin is also available as a 1 mg/ml solution in 50 
and 100 mg vials. 
7.2.3 
Pharmacology 
The dominant mode of action of cisplatin appears to involve the formation of a bifunctional adduct 
resulting in DNA crosslinks. How this kills the cell remains unclear. There are data to indicate that its 
mode and sites of action are different from those of nitrogen mustard and the standard alkylating agents.  
Plasma levels of cisplatin decay in a biphasic mode with an initial half-life of 18 to 37 minutes and a 
secondary phase ranging from 44 to 190 hours. This prolonged phase is due to protein binding which 
exceeds 90%.  Urinary excretion is incomplete with only 27 to 45% excreted in the first five days. The 
initial fractions are largely unchanged drugs. 
7.2.4 
Administration 
Cisplatin should be given immediately after preparation as a slow intravenous infusion. 
7.2.5 
Storage 
The intact vials should be stored at room temperature. Once reconstituted, the solution should be kept at 
room temperature to avoid precipitation. Due to a lack of preservatives, the solution should be used within 
8 hours of reconstitution. 
7.2.6 
Supply 
Commercially available. 
7.2.7 
Adverse Events  
• Hematologic:  Myelosuppression 
• Gastrointestinal: Nausea and vomiting; anorexia 
• Renal: Elevation of BUN and creatinine, hyperuricemia, renal tubular damage  
• Cardiac: Rare cardiac abnormalities 


24  
RTOG 0926; version date February 01, 2019 
 
 
• Neurological: Sensory (taste), peripheral neuropathy, seizures 
• Allergy: Anaphylactoid and urticarial reactions (acute); rash 
• Other: Fatigue, otoxicity including hearing loss or tinnitus, loss of muscle function 
 
7.3 
Cisplatin Dose Modifications (4/6/12) 
7.3.1 
A complete blood count and serum creatinine will be drawn at the start of weeks 1, 3, and 5 or at the end 
of the week prior.  Dose modifications for the drugs given that week will be based upon these results.  
Dose reductions based upon clinical problems such as neurotoxicity may involve discontinuation of the 
drug altogether and are specified in the text below. 
7.3.2 
Modifications for nephrotoxicity during chemoradiotherapy are as listed in the table below.  (If serum 
creatinine is out of range, but CrCl is in range, 100% can be given): 
 
Day 1 Level  
Dose 
 
Serum creatinine ≤ 1.5 mg% 
 
100% 
 
Serum creatinine > 1.33 x baseline 
 
75% 
 
Serum creatinine > 1.5 x baseline 
 
Hold cisplatin 
 
 
7.3.3 
Modifications for myelosuppression during chemoradiotherapy are as listed in the table below: 
 
% Calculated Dose 
 
 
Platelet Count 
 
 ≥ 150K  
100-149K  
75-99K  
< 75K  
 
ANC 
 (x 1000) 
≥ 1.4  
 
100 
100  
100 
75  
1.0 - <1.4  
 
100  
75  
75  
75  
< 1.0  
 
0  
0  
0  
0 
 
7.3.4 
Modification for peripheral neurotoxicity grade 3: Omit cisplatin. 
 
7.4 
Mitomycin (4/6/12) 
7.4.1 
For patients treated with mitomycin and 5FU, mitomycin will be given as an intravenous bolus dose of 12 
mg/m2 on day 1 of radiotherapy.  No additional mitomycin will be administered. 
 
7.5 
5FU (4/6/12) 
Refer to package insert for additional information. 
 
7.5.1 
Technique of Administration 
5FU will be administered as a continuous infusion at 500 mg/m2/24 hrs for 5 consecutive days during 
weeks 1 and 4 of radiation treatment (corresponding to fractions 1-5 and 16-20).  A suitable infusion 
pump will be used for this purpose.   
7.5.2 
Any desired antiemetics may be used.  Typically, simple antiemetics such as oral prochlorperazine are 
sufficient for nausea control.  
7.5.3 
Supply 
Commercially available 
 
7.6 
5FU Dose Modifications (4/6/12) 
7.6.1 
The principal toxicities of 5FU are diarrhea and mucositis.  Mild diarrhea may be controlled when 
necessary with loperamide.  If palmar desquamation occurs, this may be managed with pyridoxine 50 mg 
every other day.  Grade 4 toxicities are rare at the proposed doses, but any such occurrences should be 
immediately reported and treatment halted.  Dose modifications for diarrhea or mucositis are described in 
the table below: 


25  
RTOG 0926; version date February 01, 2019 
 
 
 
Dose Modifications for 5FU-Related Diarrhea or Mucositis 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
No change 
1.  Reduce infusion dose by 
125 mg/m2/day 
2.  Continue radiation on 
schedule 
1.  Discontinue infusion 
permanently 
2.  Consider interruption 
of radiation until 
resolution to < grade 1 
1.  Discontinue all 
therapy 
2.  Reassess weekly 
and consider 
resumption of radiation 
after resolution to < 
grade 1 
 
7.7 
Treatment Interruption (4/6/12) 
For grade 3 or greater hematologic toxicity (ANC, platelets), both radiation and chemotherapy (i.e., all 
treatment) should be held until toxicities resolve to grade 1. For radiation on hold (Section 6.8), 
chemotherapy should be held also. For a grade 3 acute colitis, cystitis, or any other grade 3 infield 
(radiation-related) toxicity during any treatment week, treatment (both radiation and chemotherapy) 
should be delayed until the toxicity subsides to the grade 2 level.  If the delay is greater than 3 weeks, 
then the patient should be considered intolerant of protocol therapy and appropriate off-protocol therapy 
given. 
 
For any grade 4 toxicity, all treatment should be held, and chemotherapy should not be resumed.  
Patients should be reassessed weekly, and radiation therapy may be restarted after resolution of toxicity 
to the grade 2 level.  If the delay is greater than 3 weeks, the patient should be considered intolerant of 
protocol therapy and appropriate off-protocol therapy given. 
 
7.8 
Modality Review (4/6/12) (3/31/14) 
The Medical Oncology Co-Chair, M. Dror Michaelson, MD PhD, will perform a Chemotherapy Assurance 
Review of all patients who receive or are to receive chemotherapy in this trial. The goal of the review is to 
evaluate protocol compliance. The review process is contingent on timely submission of chemotherapy 
treatment data as specified in Section 12.1. The scoring mechanism is: Per Protocol:Acceptable 
Variation; Unacceptable Deviation; and Not Evaluable.  A report is sent to each institution once per 
year to notify the institution about compliance for each case reviewed in that year. 
   
Dr. Michaelson will perform a review after complete data for the first 20 cases enrolled has been received 
at NRG Oncology. Dr. Michaelson will perform the next review after complete data for the next 10 cases 
enrolled has been received at NRG Oncology. The final cases will be reviewed within 3 months after this 
study has reached the target accrual or as soon as complete data for all cases enrolled has been 
received at NRG Oncology, whichever occurs first. 
 
 
 
7.9 
Adverse Events  (01-Feb-2019) 
The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse 
Events (CTCAE) version 5.0 will be utilized for AE reporting. All appropriate treatment areas should have 
access to a copy of the CTCAE version 5.0. A copy of the CTCAE version 5.0 can be downloaded from 
the CTEP web site (https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm.)  
  
 
Adverse events (AEs) that meet expedited reporting criteria defined in the table(s) below will be reported 
via the CTEP Adverse Event Reporting System (CTEP-AERS) application accessed via the CTEP web 
site (https://eapps-ctep.nci.nih.gov/ctepaers/pages/task?rand=1389817585865). 
7.9.1 
Adverse Events (AEs)  
Definition of an AE: Any untoward medical occurrence associated with the use of a drug in humans, 
whether or not considered drug related.  Therefore, an AE can be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal (investigational) product, whether or not considered related to the medicinal (investigational) 
product (attribution of unrelated, unlikely, possible, probable, or definite). (International Conference on 


26  
RTOG 0926; version date February 01, 2019 
 
 
Harmonisation [ICH], E2A, E6). [CTEP, NCI Guidelines: Adverse Event Reporting Requirements. 
February 29, 2012; 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/adverse_events.htm] 
7.9.2 
Serious Adverse Events (SAEs) — Serious adverse events (SAEs) that meet expedited reporting 
criteria defined in the table in Section 7.10 will be reported via CTEP-AERS. SAEs that require 24 hour 
CTEP-AERS notification are defined in the expedited reporting table in Section 7.10.  Contact the CTEP-
AERS Help Desk if assistance is required. 
 
Definition of an SAE: Any adverse drug event (experience) occurring at any dose that results in any of 
the following outcomes: 
• 
Death; 
• 
A life-threatening adverse drug experience; 
• 
Inpatient hospitalization or prolongation of existing hospitalization; 
• 
A persistent or significant disability/incapacity; 
• 
A congenital anomaly/birth defect; 
• 
Important medical events (IME) that may not result in death, be life threatening, or require 
hospitalization may be considered an SAE, when, based upon medical judgment, they may 
jeopardize the patient and may require medical or surgical intervention to prevent one of the 
outcomes listed in the definition.  
Due to the risk of intrauterine exposure of a fetus to potentially teratogenic agents, the pregnancy of a 
study participant must be reported via CTEP-AERS in an expedited manner.  
7.9.3 
Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) 
AML or MDS that is diagnosed as a secondary malignancy during or subsequent to treatment in patients 
on NCI/CTEP-sponsored clinical trials must be reported via the CTEP-AERS system within 30 days of 
AML/MDS diagnosis. 
 
 
Secondary Malignancy 
A secondary malignancy is a cancer caused by treatment for a previous malignancy (e.g., treatment with 
investigational agent/intervention, radiation or chemotherapy). A secondary malignancy is not considered 
a metastasis of the initial neoplasm.  
 
CTEP requires all secondary malignancies that occur following treatment with an agent under an NCI 
IND/IDE be reported via CTEP-AERS. Three options are available to describe the event: 
 
• Leukemia secondary to oncology chemotherapy (e.g., acute myelocytic leukemia [AML])  
• Myelodysplastic syndrome (MDS) 
• Treatment-related secondary malignancy 
 
Any malignancy possibly related to cancer treatment (including AML/MDS) should also be reported via 
the routine reporting mechanisms outlined in each protocol.  
 
 
Second Malignancy  
A second malignancy is one unrelated to the treatment of a prior malignancy (and is NOT a metastasis 
from the initial malignancy).  Second malignancies require ONLY routine reporting via CDUS unless 
otherwise specified. 
 
7.10 
CTEP-AERS Adverse Event Reporting Requirements (3/31/14)(3/6/2015) 
All serious adverse events that meet expedited reporting criteria defined in the reporting table below will 
be reported via CTEP-AERS, the CTEP Adverse Event Reporting System, accessed via the CTEP web 
site, 
https://eapps-ctep.nci.nih.gov/ctepaers/pages/task?rand=1389817585865. 
 
Submitting a report via CTEP-AERS serves as notification to NRG Oncology and satisfies NRG 
requirements for expedited adverse event reporting. 
 
CTEP-AERS provides a radiation therapy-only pathway for events experienced that involve radiation 
therapy only. These events must be reported via the CTEP-AERS radiation therapy-only pathway. 
 


27  
RTOG 0926; version date February 01, 2019 
 
 
In the rare event when Internet connectivity is disrupted, a 24-hour notification must be made to the NRG 
Oncology Operations Office at 1-800-227-5463, ext. 4189, for instances when Internet fails. Once internet 
connectivity is restored, an AE report submitted by phone must be entered electronically into CTEP-
AERS. 
 
• 
CTEP-AERS-24 Hour Notification requires that a CTEP-AERS 24-hour notification is 
electronically submitted within 24 hours of learning of the adverse event. Each CTEP-AERS 
24-hour notification must be followed by a CTEP-AERS 5 Calendar Day Report. Serious 
adverse events that require 24 hour CTEP-AERS notification are defined in the expedited 
reporting table below. 
• 
Supporting source document is not mandatory.  However, if the CTEP-AERS report indicates 
in the Additional Information section that source documentation will be provided, then it is 
expected.  If supporting source documentation accompanies a CTEP-AERS report, include 
the protocol number, patient ID number, and CTEP-AERS ticket number on each page, and 
fax supporting documentation to the NRG Oncology dedicated SAE FAX, 215-717-0990. 
• 
A serious adverse event that meets expedited reporting criteria outlined in the following table 
but is assessed by the CTEP-AERS System as “expedited reporting NOT required” must still 
be reported to fulfill NRG Oncology safety reporting obligations. Sites must bypass the “NOT 
Required” assessment; the CTEP-AERS System allows submission of all reports regardless 
of the results of the assessment.  
 
CTEP defines routine AE reporting requirements for phase 2 and 3 trials as described in the table below. 
Important: All AEs reported via CTEP-AERS also must be reported on the AE section of the appropriate 
case report form (see Section 12.1). 
 
Late Phase 2 and Phase 3 Studies: Expedited Reporting Requirements for Adverse Events that 
Occur on Studies Utilizing a Commercially Available Agent within 30 Days of the Last 
Administration of the Commercially Available Agents (Cisplatin, Mitomycin, 5FU)/Intervention1, 2 
 
FDA REPORTING REQUIREMENTS FOR SERIOUS ADVERSE EVENTS (21 CFR Part 312) 
NOTE:  Investigators MUST immediately report to the sponsor (NCI) ANY Serious Adverse Events, whether or not 
they are considered related to the investigational agent(s)/intervention (21 CFR 312.64) 
 An adverse event is considered serious if it results in ANY of the following outcomes:   
1) 
Death 
2) 
A life-threatening adverse event  
3) 
An adverse event that results in inpatient hospitalization or prolongation of existing hospitalization for ≥ 24 
hours  
4) 
A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions  
5) 
A congenital anomaly/birth defect.  
6) 
Important Medical Events (IME) that may not result in death, be life threatening, or require hospitalization 
may be considered serious when, based upon medical judgment, they may jeopardize the patient or 
subject and may require medical or surgical intervention to prevent one of the outcomes listed in this 
definition. (FDA, 21 CFR 312.32; ICH E2A and ICH E6). 
 
ALL SERIOUS adverse events that meet the above criteria MUST be immediately reported to the NCI via CTEP-
AERS within the timeframes detailed in the table below. 
Hospitalization 
Grade 1 
Timeframes 
Grade 2 
Timeframes 
Grade 3 Timeframes 
Grade 4 & 5 
Timeframes 
Resulting in 
Hospitalization  
≥ 24 hrs 
10 Calendar Days 
24-Hour 5 
Calendar Days 
Not resulting in 
Hospitalization  
≥ 24 hrs 
Not required 
10 Calendar Days 


28  
RTOG 0926; version date February 01, 2019 
 
 
NOTE:  Protocol specific exceptions to expedited reporting of serious adverse events are found in the Specific 
Protocol Exceptions to Expedited Reporting (SPEER) portion of the CAEPR 
Expedited AE reporting timelines are defined as: 
o “24-Hour; 5 Calendar Days” - The AE must initially be reported via CTEP-AERS within 24 hours of 
learning of the AE, followed by a complete expedited report within 5 calendar days of the initial 24-
hour report. 
o “10 Calendar Days” - A complete expedited report on the AE must be submitted within 10 calendar 
days of learning of the AE. 
1Serious adverse events that occur more than 30 days after the last administration of investigational agent/ 
intervention and have an attribution of possible, probable, or definite require reporting as follows:  
Expedited 24-hour notification followed by complete report within 5 calendar days for: 
• All Grade 4, and Grade 5 AEs 
Expedited 10 calendar day reports for: 
• Grade 2 adverse events resulting in hospitalization or prolongation of hospitalization  
• Grade 3 adverse events 
2 For studies using PET or SPECT IND agents, the AE reporting period is limited to 10 radioactive half-lives, 
rounded UP to the nearest whole day, after the agent/intervention was last administered.  Footnote “1” above 
applies after this reporting period. 
Effective Date:  May 5, 2011 
 
 
8.0 SURGERY (4/20/15) 
8.1 
Pre-Chemoradiation Evaluation 
We recommend that the endoscopic evaluation include the following: 
8.1.1 
Cystoscopy with tumor mapping on the initial Cystoscopic Report (Appendix V) 
8.1.2 
A visibly complete transurethral resection of the tumor (TURBT). Tumor specimens should be sent to the 
NRG Oncology Biospecimen Bank – San Francisco as described in Section 10.0. 
8.1.3 
After the TURBT, if possible, take one biopsy of the tumor base and two biopsies of the periphery of the 
tumor by cold cup for additional analysis of the completeness of the TURBT. 
8.1.4 
Bimanual examination before and after TURBT to evaluate possible residual tumor bulk using the 
following criteria: exam not performed, no pelvic mass, mobile pelvic mass, fixed pelvic mass. Bimanual 
examination may not be possible in some patients, such as those that are very obese.  
8.1.5 
One biopsy each from the bladder neck and from the prostatic urethra sampling the mucosa and, if the 
prostatic mucosa has a visible tumor, the stroma beneath the prostatic mucosa should also be biopsied. 
 
8.2 
Post-Chemoradiation Endoscopic Response Evaluation 
This evaluation will take place 8-10 weeks following completion of the chemoradiation.  The 
evaluation will include: cytology, cystoscopy, tumor site transurethral biopsy, and bimanual examination 
after biopsy (this latter requirement need not be met in an obese patient).  Operative reports and 
pathology reports from TURBT specimens should be submitted (see Section 12.1).  Operative reports 
should describe the surgeon’s assessment of the tumor burden in the bladder and prostatic urethra as 
well as the overall clinical stage at the conclusion of the resection.  Moreover, it should document the 
findings of the bimanual examination. The pathology report should include the gross and microscopic 
description of tumor location, tumor grade, and tumor stage using the T-classification of the TNM staging 
system.  Specifically, pathology reports should include a description of the depth of tumor invasion. 
 
8.3 
Radical Cystectomy 
For most patients who have a persistent tumor on re-evaluation following completion of the protocol, a 
radical cystectomy is recommended. In the male, radical cystectomy will include a complete en bloc 
resection of the bladder, prostate, seminal vesicles, and intramural ureters, as well as associated 
peritoneum and perivesical fat.  In the female, radical cystectomy will include resection of the bladder 
along with the intramural ureters, perivesical fat and peritoneum associated with the bladder.  Depending 
on the local extent of the tumor and urinary diversion choice of the patient, a resection of the urethra 
anterior and lateral walls of the vagina, uterus, fallopian tubes, and ovaries may also be required.   
  


29  
RTOG 0926; version date February 01, 2019 
 
 
Orthotopic diversion, continent cutaneous diversion, and incontinent cutaneous diversions are all 
permissible as jointly determined by the surgeon and patient. 
 
When feasible, total lymphadenectomy should be performed. The dissection should include resection of 
nodal tissue from the bifurcation of the common iliac vessels to the inguinal ligament and from the 
genitofemoral nerve to the hypogastric artery. Operative reports and pathology reports from cystectomy 
specimens should be submitted (see Section 12.1).  The pathology report should include the gross and 
microscopic description of tumor location, tumor grade and tumor stage using the TNM staging system.  
Specifically, pathology reports should include a description of the depth of tumor invasion, involvement of 
other organs or pelvic structure, summary of the margin status and the location and total number of lymph 
nodes resected and involved with carcinoma. 
 
8.4 
Surveillance Cystoscopies in Complete Responding Patients 
Subsequent cystoscopic evaluations will be every 3 months for the first year, every 4 months for the 
second year and every 6 months for years 3, 4, and 5, and then annually, provided there has been no 
recurrence of the tumor. These periodic evaluations will be done in accordance with the schedule in 
Section 11.0 and Appendix I and will include cytology, biopsy of the original tumor site, and biopsy of any 
suspicious areas as well as a bimanual examination. If after two re-evaluations in which the tumor site re-
biopsies have been negative and the urologist observes nothing suspicious, a cytology without biopsy is 
permitted. Regular cystoscopic follow-up will allow additional therapy to be initiated at the earliest prompt 
opportunity if relapse occurs.   
 
8.5  
Surgical Quality Assurance Reviews   
The Urology Co-Chair, Douglas Dahl, MD, will perform a Quality Assurance Review after complete data 
for the first 20 cases enrolled has been received at NRG Oncology. Dr. Dahl will perform the next review 
after complete data for the next 10 cases enrolled has been received at NRG Oncology. The final cases 
will be reviewed within 3 months after this study has reached the target accrual or as soon as complete 
data for all cases enrolled has been received at NRG Oncology, whichever occurs first. Surgical reviews 
will require detailed operative and pathology notes. 
 
9.0 OTHER THERAPY 
9.1 
Permitted Supportive Therapy (4/6/12) 
All supportive therapy for optimal medical care will be given during the study period at the discretion of 
the attending physician(s) within the parameters of the protocol and documented within each site’s source 
documents as concomitant medication. 
9.1.1 
For patients who are treated with attempted bladder preservation, either radical cystectomy or possibly, 
further intravesical drug therapy will be promptly considered for a local persistence or local re-occurrence. 
This subsequent therapy will be given at the discretion of the urologist. The rates of local recurrence 
and/or distant metastases will be reported. 
9.1.2 
For patients who develop distant metastases, additional therapies will be treated at the discretion of the 
primary physicians.   
9.1.3 
Anti-emetic regimens, which may include ondansetron, granisetron, metoclopramide, lorazepam, 
dexamethasone, diphenhydramine, hydrochloride and/or prochlorperazine, are recommended before and 
after chemotherapy administration. 
9.1.4 
The use of growth factors is permitted. 
 
10.0 
TISSUE/SPECIMEN SUBMISSION (4/20/15) 
NOTE: Patients must be offered the opportunity to participate in the correlative components of the  
study, such as tissue/specimen submission or quality of life assessment. If the patient consents to  
participate in the tissue/specimen component of the study, the site is required to submit the patient’s  
specimens as specified in Section 10.0 of the protocol. Sites are not permitted to delete the  
tissue/specimen component from the protocol or from the sample consent. 
10.1 
Tissue/Specimen Submission  
The NRG Oncology Biospecimen Bank at the University of California San Francisco acquires and 
maintains high quality specimens from NRG Oncology trials. Tissue from each block is preserved through 
careful block storage and processing. NRG Oncology encourages participants in protocol studies to 
consent to the banking of their tissue. The NRG Oncology Biospecimen Bank provides tissue specimens 


30  
RTOG 0926; version date February 01, 2019 
 
 
to investigators for translational research studies. Translational research studies integrate the newest 
research findings into current protocols to investigate important biologic questions.  
 
In this study, primary tumor tissue from the pretreatment TURBT as well as two biopsies obtained from 
the tumor periphery will be submitted to the NRG Oncology Biospecimen Bank for the purpose of tissue 
banking for biomarker studies (strongly recommended but not required). Blood and urine specimens will 
be collected for banking for future research (strongly recommended but not required). 
 
10.2 
Specimen Collection: Strongly Recommended (12/17/13)   
For patients who have consented to participate in the tissue/blood/urine component of the study 
(See sample consent). 
The following must be provided in order for the case to be evaluable by the NRG Oncology Biospecimen 
Bank:  
10.2.1 One H&E stained slide (slide can be a duplicate cut stained H&E of the diagnostic slide [block]; it does 
not have to be the diagnostic slide itself) 
10.2.2 A corresponding paraffin-embedded tissue block of the tumor or a 2 mm diameter core of tissue, punched 
from the tissue block containing the tumor with a skin punch and submitted in a plastic tube labeled with 
the surgical pathology number. NOTE: A kit with the punch, tube, and instructions can be obtained free of 
charge from the NRG Oncology Biospecimen Bank. Block or core must be clearly labeled with the 
pathology identification number and block number that corresponds to the Pathology Report. 
• 
The submitted material must be from malignant tumor, not necrotic or fibrotic tissue. If the 
submitted material is reviewed and is not tumor, the site may be assessed a protocol violation. 
10.2.3 A Pathology Report documenting that the submitted block or core contains tumor. The report must 
include the RTOG (NRG) protocol number and patient’s case number. The patient’s name and/or other 
identifying information should be removed from the report. The surgical pathology numbers and 
information must NOT be removed from the report. 
10.2.4 A Specimen Transmittal Form clearly stating that tissue is being submitted for the NRG Oncology 
Biospecimen Bank; if for translational research, this should be stated on the form. The form must include 
the RTOG (NRG) protocol number and patient’s case number.  
10.2.5 Serum, plasma, whole blood, and urine  
See Appendix VI for the blood and urine collection kits and instructions. 
The following materials must be provided to the NRG Oncology Biospecimen Bank: A Specimen 
Transmittal Form documenting the date of collection of the serum, plasma, whole blood, and urine; the 
RTOG (NRG) protocol number, the patient’s case number, and method of storage, for example, stored at 
-20° C, must be included. 
10.2.6 Storage Conditions 
 
Store at -80°C (-70°C to -90°C) until ready to ship. If a -80°C Freezer is not available:  
• 
Samples can be stored short term in a -20° C freezer (non-frost free preferred) for up to one week (please 
ship out Monday-Wednesday only). 
OR: 
• 
Samples can be stored in plenty of dry ice for up to one week, replenishing daily (ship out Monday-
Wednesday only). 
OR: 
• 
Samples can be stored in liquid nitrogen vapor phase (ship out Monday-Wednesday only). 
 
Please indicate on Specimen Transmittal Form the storage conditions used and time stored. 
 
10.2.7 Specimen Collection Summary 
 
Specimen Collection 
Specimens taken from 
patient: 
Collected when: 
Submitted as: 
 
Shipped: 
Representative H&E stained 
slides of the primary tumor 
Pre-treatment 
H&E stained slide 
Slide shipped ambient 
A paraffin-embedded tissue 
block of the primary tumor 
taken before initiation of 
treatment or a 2 mm 
Pre-treatment 
Paraffin-embedded tissue 
block or punch biopsy 
(must match the H&E slide 
being submitted) 
Block or punch shipped 
ambient 
 


31  
RTOG 0926; version date February 01, 2019 
 
 
diameter core of tissue, 
punched from the tissue 
block with a skin punch  
SERUM: 5-10 mL of whole 
blood in each of 2 red-top 
tubes and centrifuge 
Pre-treatment 
Frozen serum samples 
containing 0.5 mL per 
aliquot in 1 mL cryovials 
(five to ten)  
Serum sent frozen on dry 
ice via overnight carrier 
PLASMA: 5-10 mL of 
anticoagulated whole blood 
in EDTA tubes 
(purple/lavender top) and 
centrifuge 
Pre-treatment 
Frozen plasma samples 
containing 0.5 mL per 
aliquot in 1 mL cryovials 
(five to ten)  
Plasma sent frozen on dry 
ice via overnight carrier 
DNA: 5-10 mL of 
anticoagulated whole blood 
in EDTA tubes 
(purple/lavender top) and mix 
Pre-treatment 
Frozen whole blood 
samples containing   
1 mL per aliquot in 1ml 
cryovials  
(three to five) 
Whole blood sent frozen 
on dry ice via overnight 
carrier 
10-20 mL clean-catch urine  
 
Pre-treatment 
Two 5-10 mL urine aliquots 
in 2 sterile 15 ml 
polypropylene centrifuge 
tubes.  Store frozen at  
-20° or 80° C  
Urine sent frozen on dry 
ice via overnight carrier 
 
10.2.8 Submit materials as follows: 
U. S. Postal Service Mailing Address: For Non-Frozen Specimens Only 
NRG Oncology Biospecimen Bank 
University of California San Francisco 
Campus Box 1800 
2340 Sutter Street, Room S341 
San Francisco, CA 94143-1800 
 
Courier Address (FedEx, UPS, etc.): For Trackable FFPE and ALL Frozen Specimens 
NRG Oncology Biospecimen Bank 
University of California San Francisco 
2340 Sutter Street, Room S341 
San Francisco, CA 94115 
 
Questions: 415-476-7864/FAX 415-476-5271;  NRGBB@ucsf.edu 
 
 
 
10.3Confidentiality/Storage (01-Feb-2019) 
( 
10.3.1 
Upon receipt, the specimen is labeled with the RTOG (NRG) protocol number and the patient’s 
case number only. The NRG Oncology Biospecimen Bank database only includes the following 
information: the number of specimens received, the date the specimens were received, 
documentation of material sent to a qualified investigator, type of material sent, and the date 
the specimens were sent to the investigator. No clinical information is kept in the database. 
10.3.2 
Specimens for banking will be stored for an indefinite period of time. Specimens for the 
biomarker component of this protocol will be retained until the study is terminated, unless the 
patient has consented to storage for future studies. If at any time the patient withdraws consent 
to store and use specimens, the material will be returned to the institution that submitted it. 
 
11.0 
PATIENT ASSESSMENTS 
11.1 
Study Parameters: See Appendix I for a summary of assessments and time frames. See Section 11.2 
below for details and/or exceptions to Appendix I. 
 
11.2 
Evaluation Following Chemoradiotherapy 
11.2.1 After the first year of post-treatment follow-up, the bimanual exam under anesthesia with bladder biopsy 
may be omitted if the office cystoscopy and urine cytology are not positive. 
11.2.2 During the 3rd post-treatment year, the AUA symptom score will be obtained for patients who still have a 
native bladder. 


32  
RTOG 0926; version date February 01, 2019 
 
 
 
11.3 
Measurement of Response 
 
 
11.3.1 The objective response of the local bladder tumor will be described as follows: 
• 
Complete Response (a CR or a pT0 response) requires the absence of any tumor in the 
tumor site re-biopsy specimen or elsewhere in the bladder and a urine cytology specimen 
that is not positive. 
• 
Partial Response (PR) requires that all response criteria of a CR except the urine 
cytology remain positive.   
• 
No Response (NR) requires the continued presence of a tumor in the tumor site biopsy 
specimen or elsewhere. The depth of invasion of the persistent or recurrent tumor will be 
noted (i.e., Ta, Tis, T, or ≥ T2). 
• 
Progression requires an increase of 50% or more in the largest diameter of the 
endoscopically appreciable tumor or the progression from stage T1 to stage T2 or 
beyond. 
  11.3.2 Distant disease progression: The first appearance of disease in a non-regional lymph node, solid organ or 
bone.  This may be identified on a routine follow-up CT scan or bone scan or a study performed to work 
up a specific patient complaint.  Additional radiographic studies or biopsies may be performed at the 
discretion of the treating physician in equivocal cases but are not required.  Radiographic evidence of 
metastasis is sufficient for evaluation of this endpoint. Time to development of distant metastasis will be 
defined as the time to the first appearance of distant metastasis. 
 
11.4 
Criteria for Discontinuation of Protocol Treatment 
 
 
Progression of disease; 
 
A delay in protocol treatment, as specified in Sections 6.0 and/or 7.0 
 
If protocol treatment is discontinued, follow up and data collection will continue as specified in the 
protocol. 
 
12.0 
DATA COLLECTION  (01-Feb-2019)  
             Data collection for this study will be done exclusively through the Medidata Rave clinical data 
management system.  Access to the trial in Rave is granted through the iMedidata application to all 
persons with the appropriate roles assigned in Regulatory Support System (RSS).  To access Rave via 
iMedidata, the site user must have an active CTEP-IAM account (check at 
https://ctepcore.nci.nih.gov/iam) and the appropriate Rave role (Rave CRA, Read-Only, CRA (Lab Admin, 
SLA or Site Investigator) on either the LPO or participating organization roster at the enrolling site. 
 
Upon initial site registration approval for the study in RSS, all persons with Rave roles assigned on the 
appropriate roster will be sent a study invitation e-mail from iMedidata.  To accept the invitation, site users 
must log into the Select Login (https://login.imedidata.com/selectlogin) using their CTEP-IAM user name 
and password, and click on the “accept” link in the upper right-corner of the iMedidata page.  Please note, 
site users will not be able to access the study in Rave until all required Medidata and study specific 
trainings are completed.  Trainings will be in the form of electronic learnings (eLearnings), and can be 
accessed by clicking on the link in the upper right pane of the iMedidata screen. 
 
 
Users that have not previously activated their iMedidata/Rave account at the time of initial site registration 
approval for the study in RSS will also receive a separate invitation from iMedidata to activate their 
account.  Account activation instructions are located on the CTSU website, Rave tab under the Rave 
resource materials (Medidata Account Activation and Study Invitation Acceptance).  Additional 
information on iMedidata/Rave is available on the CTSU members’ website under the Rave tab at 
www.ctsu.org/RAVE/ or by contacting the CTSU Help Desk at 1-888-823-5923 or by e-mail at 
ctsucontact@westat.com.  
 
 
 
 
 
. 
 
Patients will be identified by initials only (first middle last); if there is no middle initial, a hyphen will be 
used (first-last). Last names with apostrophes will be identified by the first letter of the last name. 


33  
RTOG 0926; version date February 01, 2019 
 
 
 
12.1 
Summary of Data Submission (12/17/13) 
 
 
 
Item 
Due 
Demographic Form (A5) 
Within 2 weeks of study entry. 
Initial Evaluation Form (I1) 
 
Pathology Report [from TURBT] (P1) 
 
Operative Report [from TURBT] (S2) 
 
American Urological Association (AUA) Symptom 
scores (PQ) 
Within 2 weeks of study entry and then in year 
3 post treatment for patients with a native 
bladder 
 
 
 
 
Treatment Form (TF) 
Within 2 weeks after chemoradiation therapy 
is completed 
Post-treatment Evaluation Form (F0) 
Within 8-10 weeks following completion of 
chemoradiation 
Follow-up Form (F1) 
Post chemoradiation: every 3 months for (1) 
year; every 4 months for (1) year; every 6 
months for (3) years; then annually 
Surgical Form (for cystectomy) (S1) 
Within 2 weeks after surgery (if cystectomy 
done) 
Surgical Operative Note (from cystectomy) (S2) 
 
Surgical Pathology Report (from cystectomy) (S5) 
 
  
Item 
Due 
Digitally reconstructed radiographs and initial 
approved small pelvis portal images of each 
treatment field (TP) 
Within 1 week of RT start 
Must be digitally submitted in Dicom or JPEG 
format to TRIAD. See Section 12.2. 
 
 
Final Dosimetry Information: 
 
Radiotherapy Form (T1) web entry 
Within 1 week of RT end 
Complete Daily Treatment Record (T5) [Copy to 
HQs] 
Within 1 week of RT end 
NOTE: ADDITIONAL SIMULATION AND PORTAL FILMS AND/OR DIGITAL FILM IMAGES WILL BE 
KEPT BY THE INSTITUTION AND ONLY SUBMITTED IF REQUESTED. 
 
12.2 
Summary of Dosimetry Digital Data Submission (Submit to TRIAD; see Section 5.0 for  
account access and installation instructions) (12/17/13) 
 
Preliminary Dosimetry Information  
 
Digital data submission includes the following: 
 
●    CT dataset with contours for all critical normal structures, CTV, and PTVs 
●    Digital beam geometry for initial and boost beam sets 
●    Doses for initial, boost and composite sets of concurrently treated beams 
• 
Digital DVH data for all required critical normal structures, CTV, and PTVs for 
total dose plan 
• 
All required structures MUST be labeled per the table in Section 6.4. 
• 
Digitally reconstructed radiographs and initial approved small pelvis portal 
 
 
 
 
Within 1 
week of 
start of RT 


34  
RTOG 0926; version date February 01, 2019 
 
 
images of each treatment field in JPEG format (TP) 
• 
Digital Data Submission Information (DDSI) Form 
Upon submission of the digital data via TRIAD, complete an online Digital Data 
Submission Information (DDSI) Form  
http://www.rtog.org/CoreLab/RTQASubmissionInformation.aspx 
 
 
13.0 
STATISTICAL CONSIDERATIONS 
13.1  
Study Endpoints 
13.1.1 Primary Endpoint 
The rate of freedom from radical cystectomy at 3 years 
13.1.2   Secondary Endpoints 
• 
To assess the following clinical outcomes: 
o Rate of freedom from radical cystectomy at 5 years 
o Rate of freedom from the development of distant disease progression at 3 and 5 years 
o Rate of freedom from progression of bladder tumor to stage T2 or greater at 3 and 5 years 
o Disease-specific survival at 5 years 
o Overall survival  
• 
Incidence of adverse events (based on the CTEP Active Version of the CTCAE) 
• 
Recurrence rate of any local bladder tumor  
• 
Collection of pretreatment and post-treatment tissue, blood, and urine specimens for translational 
studies and for correlation with response and clinical outcome 
• 
Descriptive analysis for AUA symptom score at baseline and 3 years 
 
13.2 
Sample Size 
It is hypothesized that this treatment will result in a 3-year freedom from radical cystectomy rate 
of 75%. A lower bound of 60% on the confidence interval for the 3-year freedom from radical 
cystectomy rate will be promising enough to pursue this regimen further. A sample size of 33 
analyzable patients will provide a one-sided 97.5% confidence interval around the hypothesized 
75% three-year freedom from radical cystectomy rate with a lower-bound of 60%. In terms of type 
I error, this design provides a 2.5% chance of observing a 3-year freedom from radical 
cystectomy rate of less than 60% if the true rate is 75%. Adjusting the sample size for ineligible or 
dropout cases by 10%, a total of 37 patients are needed for this study. 
 
13.3 
Accrual and Duration(3/6/2015) 
At the time of trial design the legacy cooperative group of RTOG (now NRG Oncology) had no prior 
experience with accrual of patients with non-muscle invading bladder cancer.  Thus it seems wise to state 
that the accrual rate will be likely at the level of one patient per month. However, a questionnaire returned 
by the principal investigators of our full membership institutions and our affiliate membership institutions 
who have accrued previously to bladder studies indicate accrual will be twice this estimate. Assuming the 
accrual to this study will be 37 patients, this trial should complete accrual within 3 years.  
 
13.4 
Analysis Plan 
13.4.1  Primary Analysis 
The primary analysis will be performed when all eligible patients have at least 3 years of follow-up. The 
rate of freedom from radical cystectomy at 3 years is defined as the proportion of patients who have not 
had a radical cystectomy by 3 years among all eligible patients.  
 
This rate will be evaluated based on a 1-sided 97.5% confidence interval. If the bottom of the confidence 
interval is at least 0.60, then the regimen will be considered promising enough to warrant further 
investigation. If the bottom of the confidence interval is less than 0.25, then the regimen will not be 
considered any further. If the bottom of the confidence interval is anywhere between 0.25 and 0.59, the 
investigators will consider the possibility of further investigations of this regimen. 
13.4.2  Secondary Analysis 
• 
Analysis Plan for Clinical Outcomes 


35  
RTOG 0926; version date February 01, 2019 
 
 
All eligible patients who received protocol treatment will be included in the outcome analyses. The 
rates of freedom from radical cystectomy at 5 years will be estimated by a proportion; logistic 
regression will be used to model the distribution of freedom from radical cystectomy at both 3 and 
5 years; both unadjusted and adjusted odds ratios and respective 95% confidence interval will be 
computed.  All other secondary clinical outcome endpoints will be estimated as time-to-event 
endpoints. The time to failure will be measured from the date of registration to the date of the 
event of interest. Z-statistics will be used for the rate of freedom from radical cystectomy at 5 
years. The rates of freedom from distant metastasis and disease-specific survival will be 
estimated by using cumulative incidence20 of the event of interest, taking into account the 
informative nature of censoring due to competing risks. Overall survival will be estimated using 
the Kaplan-Meier method.21 All time-to-event endpoints will be modeled by Cox proportional 
hazard regression22 with appropriate clinical and demographic variables. 
• 
Evaluation of Grade 3+ Adverse Events 
Tabulation of adverse events will be reported by type, grade, and attribution of adverse event 
based on the CTEP Active Version of the CTCAE. The grade 3+ adverse event rate is defined as 
the proportion of patients who have adverse events among all eligible patients. 
 
Logistic regression will be used to model the distribution of grade 3+ adverse events. Both 
unadjusted and adjusted odd ratios and the respective 95% confidence interval will be computed. 
The time to grade 3+ adverse events will be estimated using the cumulative incidence method.20 
Death without a grade 3+ adverse event will be considered as a competing risk. Alive patients 
without acute grade 3+ adverse events will be censored at the time of analysis. 
• 
Evaluation of Recurrence Rate of Any Local Bladder Tumor 
The recurrence rate of any local bladder tumor is defined as the proportion of patients who have 
local bladder tumor recurrence. This proportion will be estimated. Logistic regression will be used 
to model the distribution. Both unadjusted and adjusted odds ratios and respective 95% 
confidence interval will be computed. 
• 
Analysis Plan for AUA Symptom Score 
AUA symptom score will be collected at baseline and 3 years for information regarding bladder 
capacity, compliance, detrusor instability and leak pressures, and a partial assessment of “bother 
factor” from the symptom score. The change from baseline to 3 years for each patient will be 
calculated and descriptive statistics (mean, median, and standard deviation) will be calculated. 
• 
Early Stopping Due to Adverse Events  
The study will be monitored by the CDUS version 3.0. If at any time a grade 5 adverse event 
definitely, probably, or possibly related to treatment is reported, it will be reviewed by the study 
chairs, the study statistician, the NRG Oncology GU cancer committee chair, or other appropriate 
NRG Oncology Leadership as needed. Case report forms, source documentation, and a 
statistical report summarizing the study will be reviewed as soon as possible. During this review, 
accrual will be suspended if necessary. Following this review, the study chairs, the study 
statistician, the NRG GU cancer committee chair, and the NRG executive committee will discuss 
the findings and make a decision about amending the protocol and/or continuing the study. 
• 
Interim Reports 
Interim reports will be prepared every six months until the final analysis. In general, the interim 
reports will include information about: 
• 
Patient accrual rate with projected completion rate; 
• 
Pretreatment characteristics of patients accrued; 
• 
Compliance rate of treatment per protocol; and  
• 
Frequency and severity of adverse events due to radiation therapy and 
chemotherapy. 
• 
CDUS Reporting 
This study will be monitored by the Clinical Data Update System (CDUS) version 3.0. Cumulative 
CDUS data will be submitted quarterly by electronic means. Reports are due January 31, April 
30, July 30, and October 31.   
 
13.5 
Gender and Minorities 
In conformance with the National Institutes of Health Revitalization Act of 1993 with regard to the 
inclusion of women and minorities in clinical research, the possible difference in any of the above 


36  
RTOG 0926; version date February 01, 2019 
 
 
endpoints between men and women, or whites and non-whites, will be investigated. The prior RTOG 
bladder cancer trial, 0233, accrued about 1% Hispanic, 7% non-white patients and 16% women. With the 
proposed 37 evaluable patients, there will not be enough statistical power to detect the difference in the 
primary endpoint between race groups and/or gender groups. Nonetheless, the descriptive statistics for 
each of these groups will be reported. 
 
 
 
Projected Distribution of Gender and Minorities 
 
 
Gender 
Ethnic Category 
Females 
Males 
Total 
Hispanic or Latino 
0 
1 
1 
Not Hispanic or Latino 
7 
29 
36 
Ethnic Category: Total of all subjects 
7 
30 
37 
 
Gender 
Racial Category 
Females 
Males 
Total 
American Indian or Alaskan Native 
0 
1 
1 
Asian 
0 
0 
0 
Black or African American 
1 
2 
3 
Native Hawaiian or other Pacific Islander 
0 
0 
0 
White 
6 
27 
33 
Racial Category: Total of all subjects 
7 
30 
37 
 


37  
RTOG 0926; version date February 01, 2019 
 
 
 
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Trimodality therapy for patients with muscularis propria-invasive bladder cancer and who are cystectomy 
candidates—the Massachusetts General Hospital and Radiation Therapy Oncology Group experiences. 
Semin Radiat Oncol. 15: 36-41, 2005. 
2. Harland SJ, Kynaston, H., Grigor K., et al., A randomized trial of radical radiotherapy for the Management 
of pT1G3 NxM0 Transitional Cell Carcinoma of the Bladder. J Urol 2007; 178: 807-813. 
3. Pansadoro, V and Emilliozzi, P T1G3 Bladder Carcinoma, Text Book of Bladder Cancer,  Eds Lerner SP, 
et al. p. 387-396. London: Taylor & Francis, 2006. 
4. Heney, NM, Ahmed, S, Flanagan, MJ et al. Superficial bladder cancer: progression and recurrence. J 
Urol, 130: 1083-1086, 1983. 
5. Herr, HW., Schwalb, DM., Zhang ZE., et al.  Intravesical Bacillus Calmenttle-Guerin Therapy Prevents 
Tumor Progression and Death from Superficial Bladder Cancer. Ten year follow up of a prospective 
randomized trial. J. Clinic. Oncol., 113: 1404-1408; 1995. 
6. Bianco, FJ., Justa D., Grignon, DJ., et al.  Management of Clinical T1 Bladder Transitional Cell 
Carcinoma by Radical Cystectomy.  Urol. Concol., 22:290-294, 2004. 
7. Stein, JP., Skinner, DG.,  Radical Cystectomy.  In:  Textbook of Genitourinary Oncology, 3rd Edition (Eds. 
Vogelzang NJ, Scardino PT, Shipley, WU., DeBruyne FMJ., Linehan  WM), Lippincott, Williams & Wilkins, pp. 
486-499, 2005. 
8. Sylvester, RJ, van der Mejiden, AP, Oosterlinck, W, et al.  Predicting recurrence and progression in 
individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 
patients from seven EORTC trials. Eur Urol, 49: 466- 465; discussion 475-467, 2006. 
9. Luciani LG, Neulander e, Murphy WM, Wajsman Z. Risk of continued intravesical therapy and delayed 
cystectomy in BCG-refractory superficial bladder cancer; an investigational approach. Urology 2001; 58: 376 
9. 
10. O’Donnell MA, Lilli K, Leopold C, National Bacillus Calmette-Guerin/Interferon Phase 2 Investigator 
Group. Interim results from national multicenter Phase II trial of combination bacillus Calmett-Guerin plus 
interferon alfa-2b for superficial bladder cancer.  J of Urol 2004; 172: 8988, 93. 
11. Lambert EH, Pierozarzio PM, Olsson CA, Benson MC, McKiernan JM, Poon S.  The Increasing Use of 
Intravesical Therapies for stage T1 Bladder cancer coincides with decreasing survival after cystectomy.  FJU 
Int 2007; 100: 33 36. 
12. Monte JE., Kuzel, TM., and Shipley WU (writing committee).  The NCCN Bladder Cancer Clinical Practice 
Guidelines in Oncology.  J. National Comprehensive Cancer Network, Volume 7; 8-37, 2009. 
13. Weiss, C., Wolze, C., Engehausen, D.G., et al.  Radiochemotherapy after transurethral resection for high-
risk T1 bladder cancer: an alternative to intravesical therapy or early cystectomy?   J Clin Oncol. 24:  2318-
2324, 2006. 
14. Shipley, WU., Kaufman, DS., Zehr, E., et al.  Selective bladder preservation by combined modality 
protocol treatment:  long-term outcomes of 190 patients with invasive bladder cancer. Urology, 60; 62-677:  
2002. 
15. Wo, JY., Shipley, WU., Dahl, DM., Coen, JJ., Heney, NM., Kaufman, DS., Zietman, AL. Trimodality 
Therapy with transurethral surgery and concurrent chemotherapy and radiation for BCG failed T1 bladder 
cancer: Is cystectomy always necessary? British Journal of Urology International, Volume 104: 179-183, 
2009. 
16. Efstathiou, JA., Bae, K., Shipley, WU., Kaufman, DS., Hagan, MP., Heney, NM., and Sandler, HM., Late 
Pelvic Toxicity after bladder-sparing therapy in patients with invasive bladder cancer: RTOG 89-93, 95-06, 97-
06, 99-06.  J Clin Oncol. 27: 4055-4061, 2009. 


38  
RTOG 0926; version date February 01, 2019 
 
 
17. Cowen, RA., McBain, CA., Ryder, WD., et al. Radiotherapy for muscle-invasive  carcinoma of the 
bladder:  results of a randomized trial comparing conventional whole  bladder with dose-escalated partial 
bladder radiotherapy.  Int. J. Radiat. Oncol. Biol. Phys.  59: 197-207, 2004. 
18.  Oh, KS., Soto, DE., Smith, DC., Montie, JE., Lee, CT., Sandler, HM.,  Combined- modality therapy with 
Gemcitabine and radiotherapy has a bladder preserving strategy: final results of a Phase I trial presented at 
the 2008 Genitourinary Cancer Symposium, February 14-16, 2008, San Francisco, California, Abstract 
number 290; 
19. Hagan, MP., Winter, KA., Kaufman, DS., et al.:  RTOG 97-06: initial report of a phase I-II  trial of selective 
bladder conservation using TURBT, twice-daily accelerated irradiation sensitized with cisplatin, and adjuvant 
MCV combination chemotherapy. Int J Radiat Oncol Biol Phys., 57:665, 2003. 
20. Kalbfleisch, JD., Prentice, RL. The statistical analysis of failure time data. New York, John Wiley & Sons, 
p.167-169, 1980. 
21. Kaplan, EL., Meier, P. Nonparametric estimation from incomplete observations. J Am Stat Assoc., 53:447-
457, 1958. 
22. Cox, DR. Regression models and life tables. J Royal Statistics Soc., 34:187-220, 1972. 


39  
RTOG 0926; version date February 01, 2019 
 
 
APPENDIX I: STUDY PARAMETER TABLE: Pre-Study Assessments (3/31/14) 
 
Pre-Study Assessments 
(may be required for eligibility) 
“Outside” pathology/cytology evaluation 
See Section 4.1.1 
Body Surface Area 
x 
History/Physical 
x 
Weight 
x 
Zubrod Status 
x 
TURBT 
x 
Cystoscopy 
x 
Bimanual exam under anesthesia 
x 
Bladder Biopsy 
x 
CBC w/diff, Platelets 
x 
Serum Creatinine  
x 
Bilirubin, Alk Phos. 
x 
GFR 
x 
SGOT, LDH, BUN 
x 
Magnesium, Calcium 
x 
Pregnancy Test 
x 
CT Scan 
x 
IVP  
Optional 
Bone Scan  
Optional 
Chest X-ray 
x 
AUA SI 
x 
-Continued on next page- 
 


40  
RTOG 0926; version date February 01, 2019 
 
 
 
APPENDIX I, STUDY PARAMETER TABLE:  Assessments During ChemoRT 
 
 
Before each 
chemotherapy cycle 
Weekly 
Final treatment day 
Weight 
 
x 
 
Zubrod Status 
 
 
x 
CBC w/diff, 
Platelets 
 
x 
 
Serum 
Creatinine 
x 
 
 
Adverse event 
evaluation  
x 
-Continued on next page- 
 
APPENDIX I, STUDY PARAMETER TABLE:  Assessments in Follow Up 
*See Section 11.2 for details. 
 
 
8-10 weeks 
Post-ChemoRT 
 
Post-treatment 
Follow-Up 
 q 3 mos in 1st yr; q 4 mos in 2nd yr; q 6 mos 
for yrs 3, 4, and 5; then annually 
History/Physical 
 
x 
Weight 
 
x 
Zubrod Status 
 
x 
Cystoscopy 
x 
x 
Urine Cytology 
x 
x 
Bimanual exam 
under 
anesthesia 
x 
x* 
Bladder Biopsy 
x 
x* 
CBC w/diff, 
Platelets 
 
x 
Serum 
Creatinine  
 
x 
CT Scan 
 
Yearly for the first 3 years 
Chest X-ray 
 
Yearly for the first 3 years 
AUA SI 
 
3rd post-treatment yr* 
Adverse event 
evaluation 
x 
x 
 


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RTOG 0926; version date February 01, 2019 
 
 
APPENDIX II 
 
ZUBROD PERFORMANCE 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 
work of a light or sedentary nature.  For example, 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 50% or more of 
waking hours 
 
4 
Completely disabled. Cannot carry on self-care. Totally confined to bed 
 
5 
Death 
 
 
 
 


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RTOG 0926; version date February 01, 2019 
 
 
APPENDIX III(3/6/2015) 
AJCC Staging System, 6th Edition 
Bladder 
 
DEFINITION OF TNM 
 
Primary Tumor (T) 
 
TX 
Primary tumor cannot be assessed 
T0 
No evidence of primary tumor 
Ta 
Noninvasive papillary carcinoma 
Tis 
Carcinoma in situ:  "flat tumor" 
T1 
Tumor invades subepithelial connective tissue 
T2 
Tumor invades muscle 
 
T2a Tumor invades superficial muscle (inner half)* 
 
T2b Tumor invades deep muscle (outer half)* 
T3 
Tumor invades perivesical tissue 
 
T3a  microscopically 
 
T3b macroscopically (extravesical mass) 
T4 
Tumor invades any of the following: prostate, uterus, vagina, pelvic wall, abdominal wall 
 
T4a Tumor invades the prostate, uterus, vagina 
 
T4b Tumor invades the pelvic wall, abdominal wall 
 
*For clinical staging based on the TURBT tissue it is commonly not possible for the pathologist to distinguish 
between cT2a and cT2b, so the protocol plan will be to group cT2a and cT2b together as all cT2 
 
Regional Lymph Nodes (N) 
 
Regional lymph nodes are those within the true pelvis; all others are distant nodes. 
 
NX 
Regional lymph nodes cannot be assessed 
N0 
No regional lymph node metastasis 
N1 
Metastasis in a single lymph node, 2 cm or less in greatest dimension 
N2 
Metastasis in a single lymph node, more than 2 cm but not more than 5 cm in greatest dimension; or 
multiple lymph nodes, none more than 5 cm in greatest dimension 
N3 
Metastasis in a lymph node more than 5 cm in greatest dimension 
 
Distant Metastasis (M) 
 
MX 
Distant metastasis cannot be assessed 
M0 
No distant metastasis 
M1 
Distant metastasis 
 
STAGE GROUPING 
Stage 0a 
Ta 
N0 
M0 
Stage 0is 
Tis 
N0 
M0 
Stage I 
T1 
N0 
M0 
Stage II 
T2a 
N0 
M0 
 
T2b 
N0 
M0 
Stage III 
T3a 
N0 
M0 
 
T3b 
N0 
M0 
 
T4a 
N0 
M0 


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RTOG 0926; version date February 01, 2019 
 
 
APPENDIX III (continued) 
 
AJCC Staging System, 6th Edition 
Bladder  
 
Stage IV 
T4b 
N0 
M0 
 
Any T 
N1 
M0 
 
Any T 
N2 
M0 
 
Any T 
N3 
M0 
 
Any T 
Any N 
M1 
 
HISTOPATHOLOGIC TYPE 
 
The histologic types are: 
 
Transitional cell carcinoma (urothelial) 
 
In situ 
 
 
Papillary 
 
 
Flat 
 
With squamous metaplasia 
 
With glandular metaplasia 
 
With squamous and glandular metaplasia 
Squamous cell carcinoma 
Adenocarcinoma 
Undifferentiated carcinoma 
 
 
HISTOPATHOLOGIC GRADE (G) 
 
GX 
Grade cannot be assessed 
G1 
Well differentiated 
G2 
Moderately differentiated 
G3-4 
Poorly differentiated or undifferentiated 
 
 
 
 
 
 
 


44  
RTOG 0926; version date February 01, 2019 
 
 
APPENDIX IV 
SMALL PELVIC FIELDS 


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RTOG 0926; version date February 01, 2019 
 
 
APPENDIX V(3/6/2015) 
CYSTOSCOPY REPORT FORM 
 
PDF form (attached) to be incorporated into PDF version of protocol that will be posted on RTOG legacy website. 
 
 
 


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RTOG 0926; version date February 01, 2019 
 
 
APPENDIX VI (4/20/15) 
Appendices for NRG Oncology Biospecimen Collection 
FFPE Specimen Plug Kit Collection 
Blood Collection Kit Instructions 
Urine Collection Kit Instructions 
 
Shipping Instructions: 
U.S. Postal Service Mailing Address: For FFPE or Non-frozen Specimens Only 
NRG Oncology Biospecimen Bank 
University of California San Francisco 
Campus Box 1800 
2340 Sutter Street, Room S341 
San Francisco, CA 94143-1800 
Courier Address (FedEx, UPS, etc.): For Frozen or Trackable Specimens 
NRG Oncology Biospecimen Bank 
University of California San Francisco 
2340 Sutter Street, Room S341 
San Francisco, CA 94115 
 
 
Include all NRG Oncology paperwork in pocket of biohazard bag.  
 
Check that the Specimen Transmittal Form (STF) has the consent boxes checked off.  
 
Check that all samples are labeled with the RTOG (NRG) study and case number, and include date of 
collection as well as collection time point (e.g., pretreatment, post-treatment). 
 
 
FFPE Specimens: 
o Slides should be shipped in a plastic slide holder/slide box. Place a small wad of padding in top of the 
container. If you can hear the slides shaking it is likely that they will break during shipping.  
o FFPE Blocks can be wrapped with paper towel, or placed in a cardboard box with padding. Do not wrap 
blocks with bubble wrap. Place padding in top of container so that if you shake the container the blocks 
are not shaking. If you can hear the slides shaking it is likely that they will break during shipping.   
o Slides, Blocks, or Plugs can be shipped ambient or with a cold pack either by United States Postal 
Service (USPS) to the USPS address (94143) or by Courier to the Street Address (94115). Do NOT 
ship on Dry Ice. 
 
 
Frozen Specimens: 
o Multiple cases may be shipped in the same cooler, but make sure each one is in a separate bag and 
clearly identified. 
o Place specimens and absorbent shipping material in Styrofoam cooler filled with dry ice (at least 7 lbs). 
There should be plenty of dry ice under and above the specimens. If the volume of specimens is 
greater than the volume of dry ice then ship in a larger Styrofoam box, or two separate boxes. Any 
Styrofoam box can be used, as long as it is big enough. 
o Specimens received thawed due to insufficient dry ice or shipping delays will be discarded and the site 
will be notified.  
o Send frozen specimens via overnight courier to the address above. Specimens should only be shipped 
Monday through Wednesday (Monday-Tuesday for Canada) to prevent thawing due to delivery delays. 
Saturday or holiday deliveries cannot be accepted. Samples can be stored frozen at -80° C until ready 
to ship. 
 
 
For Questions regarding collection/shipping please contact the NRG Oncology Biospecimen Bank 
– San Francisco by e-mail: NRGBB@ucsf.edu or phone: 415-476-7864 or Fax: 415-476-5271.


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RTOG 0926; version date February 01, 2019 
 
 
Appendix VI (continued) 
NRG ONCOLOGY FFPE SPECIMEN PLUG KIT INSTRUCTIONS 
 
This Kit allows sub-sampling of an FFPE block for submission to the NRG Oncology Biospecimen Bank – 
San Francisco. The plug kit contains a shipping tube and a punch tool.    
 
Step 1 
If the block is stored cold, allow it to equilibrate for 30 minutes at room 
temperature. Place the punch tool on the paraffin block over the selected 
tumor area. (Ask a pathologist to select area with tumor.) Push the punch 
into the paraffin block. Twist the punch tool once around to separate the 
plug from the block. Then pull the punch tool out of the block. The punch 
should be filled with tissue sample. 
 
 
 
Step 2 
Label the punch tool with the proper specimen ID.  DON’T remove specimen 
from the punch. 
 
 
Use a separate punch tool for every specimen. Call or e-mail us if you have 
any questions or need additional specimen plug kits. 
 
 
 
 
 
Step 3 
Once punch tool is labeled, place in shipping tube and mail to address 
below. Please do not mix specimens in the same tube.    
 
 
 
   
 
We will remove core specimen from the punch, embed in a paraffin block, and label with specimen ID. 
 
*NOTE: If your facility is uncomfortable obtaining the plug but wants to retain the tissue block, please send the 
entire block to the NRG Oncology Biospecimen Bank – San Francisco and we will sample a plug from the block 
and return the remaining block to your facility.  Please indicate on the submission form the request to perform the 
plug procedure and return of the block. 
 
Ship specimen plug kit, specimen in punch tool, and all paperwork to the address below. For Questions 
regarding collection/shipping or to order an FFPE Specimen Plug Kit, please contact the NRG Oncology 
Biospecimen Bank – San Francisco by e-mail: NRGBB@ucsf.edu or call 415-476-7864/Fax 415-476-5271. 
 
U.S. Postal Service Mailing Address: For Non-frozen Specimens Only 
NRG Oncology Biospecimen Bank 
University of California San Francisco 
Campus Box 1800 
2340 Sutter Street, Room S341 
San Francisco, CA 94143-1800 
 
 
 
 


48  
RTOG 0926; version date February 01, 2019 
 
 
Courier Address (FedEx, UPS, etc.): For Frozen Specimens or Trackable shipments 
NRG Oncology Biospecimen Bank 
University of California San Francisco 
2340 Sutter Street, Room S341 
San Francisco, CA 94115 


49  
RTOG 0926; version date February 01, 2019 
 
 
APPENDIX VI (continued) 
NRG ONCOLOGY BLOOD COLLECTION KIT INSTRUCTIONS 
This Kit is for collection, processing, storage, and shipping of serum, plasma, or whole blood (as 
specified by the protocol): 
 
Kit contents: 
• 
One Red Top tube for serum (A) 
• 
One Purple Top EDTA tube for plasma (B) 
• 
One Purple Top EDTA tube for Whole Blood (C) 
• 
Twenty-five (25) 1 ml cryovials 
• 
Biohazard bags (3) and Absorbent shipping material (3) 
• 
Styrofoam container (inner) and Cardboard shipping (outer) box 
• 
UN1845 DRY Ice Sticker and UN3373 Biological Substance Category B Stickers 
• 
Specimen Transmittal Form (STF) and Kit Instructions 
 
PREPARATION AND PROCESSING OF SERUM, PLASMA AND WHOLE BLOOD: 
(A) Serum (if requested): Red Top Tube 
 
Label as many 1ml cryovials (5 to 10) as necessary for the serum collected. Label them with the 
RTOG (NRG) study and case number, collection date, time, and time point, and clearly mark 
cryovials “serum”. 
Process: 
1. Allow one red top tube to clot for 30 minutes at room temperature. 
2. Spin in a standard clinical centrifuge at ~2500 RPM for 10 minutes at 4°C (preferred). If sites are 
unable to process samples at 4°C then spinning at room temperature is acceptable if done within 2 
hours of draw but must be noted on the STF. 
3. Aliquot 0.5 ml serum into as many cryovials as are necessary for the serum collected (5 to 10) 
labeled with RTOG (NRG) study and case numbers, collection date/time, protocol time-point collected 
(e.g. pretreatment, post-treatment), and clearly mark specimen as “serum”. 
4. Place cryovials into biohazard bag and immediately freeze at -70 to -90° C, and store frozen until 
ready to ship. See below for storage conditions. 
5. Store serum at -70 to -90° C until ready to ship on dry ice. See below for storage conditions. 
 
PLEASE MAKE SURE THAT EVERY SPECIMEN IS LABELED and include collection time point on the STF. 
 
(B) Plasma (If requested): Purple Top EDTA tube #1 
 
Label as many 1ml cryovials (5 to 10) as necessary for the plasma collected. Label them with the 
RTOG (NRG) study and case number, collection date, time, and time point, and clearly mark 
cryovials “plasma”. 
Process: 
1. After collection, invert tube(s) multiple times to ensure adequate mixing of EDTA. 
2. Centrifuge specimen(s) within one hour of collection in a standard clinical centrifuge at ~2500 RPM 
for 10 minutes at 4°C (preferred). If sites are unable to process samples at 4°C then spinning at room 
temperature is acceptable if done within 2 hours of draw but must be noted on the STF..  
3. If the interval between specimen collection and processing is anticipated to be more than one hour, 
keep specimen on ice until centrifuging is performed. 
4. Carefully pipette and aliquot 0.5 ml plasma into as many cryovials as are necessary for the plasma 
collected (5 to 10)  labeled with RTOG (NRG) study and case numbers, collection date/time, time point 
collected and clearly mark specimen as “plasma”.  Avoid pipetting up the buffy coat layer. 
5. Place cryovials into biohazard bag and immediately freeze at -70 to -90°C. 
6. Store frozen plasma until ready to ship on dry ice.  
7. See below for storage conditions. 
 
PLEASE MAKE SURE THAT EVERY SPECIMEN IS LABELED and include collection time point on the STF. 
 
(continued on next page) 


50  
RTOG 0926; version date February 01, 2019 
 
 
APPENDIX VI (continued) 
NRG ONCOLOGY BLOOD COLLECTION KIT INSTRUCTIONS 
 
 
 
 
 
 
 
 
 
 
 
 
 
(C) Whole Blood for DNA (if requested): Purple Top EDTA tube #2 
 
Label as many 1ml cryovials (3 to 5) as necessary for the whole blood collected..Label them with the 
RTOG (NRG) study and case number, collection date/time, and time point, and clearly mark cryovials 
“blood”. 
 
Process: 
1. After collection, invert tube(s) multiple times to ensure adequate mixing of EDTA. Blood can also be 
mixed for 5 minutes on a mixer at room temperature. 
2. Carefully pipette and aliquot 1.0 ml blood into as many cryovials as are necessary for the blood 
collected (3 to 5) labeled with RTOG (NRG) study and case numbers, collection date/time, time point 
collected and clearly mark specimen as “blood”. 
3. Place cryovials into biohazard bag and freeze immediately at -70 to -80° Celsius. 
4. Store blood samples frozen until ready to ship on dry ice.  
5. See below for storage conditions. 
 
PLEASE MAKE SURE THAT EVERY SPECIMEN IS LABELED and include collection time point on STF. 
 
Freezing and Storage: 
 Freeze Blood samples in a -80°C Freezer or on Dry Ice or snap freeze in liquid nitrogen. 
 
Store at –80°C (-70°C to -90°C) until ready to ship.  
If a -80°C Freezer is not available,  
 
Samples can be stored short term in a -20°C freezer (non-frost free preferred) for up to 
one week (please ship out Monday-Wednesday only; Canada: Monday-Tuesday only). 
OR: 
 
Samples can be stored in plenty of dry ice for up to one week, replenishing daily (please 
ship out on Monday-Wednesday only; Canada: Monday-Tuesday only). 
OR: 
 
Samples can be stored in liquid nitrogen vapor phase (ship out Monday-Wednesday only; 
Canada: Monday-Tuesday only). 
 
Please indicate on Specimen Transmittal Form the storage conditions used and time stored. 
 
Shipping/Mailing: 
 
Ship specimens on Dry Ice overnight Monday-Wednesday (Monday-Tuesday from Canada) to prevent 
thawing due to delivery delays. Saturday and holiday deliveries cannot be accepted.  
 
Include all NRG Oncology paperwork in a sealed plastic bag and tape to the outside top of the Styrofoam 
box. 
 
Wrap frozen specimens of same type (i.e., all serum together, plasma together and whole bloods 
together) in absorbent shipping material and place each specimen type in a separate biohazard bag.  
Place specimen bags into the Styrofoam cooler and fill with plenty of dry ice (7-10 lbs/3.5kg minimum).  
Add padding to avoid the dry ice from breaking the tubes.  
(continued on next page) 


51  
RTOG 0926; version date February 01, 2019 
 
 
 
Place Styrofoam coolers into outer cardboard box, and attach shipping label and UN3373 and UN1895 
stickers to outer cardboard box.    
 
 
 
 
 
Multiple cases may be shipped in the same cooler, but make sure each one is in a separate bag and that 
there is enough room for plenty of dry ice. Add padding to avoid the dry ice from breaking the tubes. 
 
For questions regarding collection, shipping or to order a Blood Collection Kit, please e-mail 
NRGBB@ucsf.edu or call (415)476-7864. 
 
Shipping Address: 
Courier Address (FedEx, UPS, etc.): For all Frozen Specimens 
NRG Oncology Biospecimen Bank 
University of California San Francisco 
2340 Sutter Street, Room S341 
San Francisco, CA 94115 
For questions, call 415-476-7864 or e-mail:  NRGBB@ucsf.edu 
  


52  
RTOG 0926; version date February 01, 2019 
 
 
APPENDIX VI (continued) 
NRG ONCOLOGY URINE COLLECTION KIT INSTRUCTIONS 
This Kit is for collection, processing, storage, and shipping of urine specimens. 
 
Kit Contents: 
• 
One (1) Sterile Urine collection cup 
• Two 15 ml polypropylene centrifuge tubes 
• 
Two 7 ml disposable pipettes 
• Biohazard bags 
• 
Absorbent paper towel 
• Parafilm for sealing outside of tubes 
 
Preparation and Processing of Urine Specimens: 
Process: 
• 
A clean catch urine specimen will be collected. To collect the specimen, use the following instructions: 
o 
Males should wipe clean the head of the penis and females need to wipe between the labia with soapy 
water/cleansing wipes to remove any contaminants.  
o 
After urinating a small amount into the toilet bowl to clear the urethra of contaminants, collect a sample of 
urine in the collection cup. 
o 
After 10-25 mL urine has been collected, remove the container from the urine stream without stopping the 
flow of urine. 
o 
Finish voiding the bladder into the toilet bowl. 
• 
Aliquot 5-10 mls of Urine into each of two 15 ml polypropylene centrifuge tubes (disposable pipets are provided 
in the kit). Do not fill with more than 10 mls to avoid cracking of tubes due to expansion during freezing. Replace 
the cap and tighten on the tubes. Make sure the cap is not cross-threaded or placed on incorrectly or leaking will 
occur.  
• 
Use parafilm to seal the cap around the outside rim of the urine tube to prevent leakage.  
• 
Discard remaining Urine and collection cup. 
• 
Label the specimen with the RTOG (NRG) study and case number, collection date and time, time point of 
collection, and clearly mark specimens as “urine”. 
• 
Wrap Urine Tubes with absorbent material (paper towels) and place into biohazard bag and seal the bag. Freeze 
and store Urine samples in a -20°C or -80°C freezer until ready to ship. 
 
PLEASE MAKE SURE THAT EVERY SPECIMEN IS LABELED with RTOG (NRG) study and case numbers, 
collection date/time, and time point collected (e.g. pretreatment, post-treatment). 
 
Storage and Shipping: 
Freezing and Storage: 
 
Urine specimens may be sent in batches or with other frozen biospecimens, if within 30-60 days of collection. Store at 
-20°C or -80°C (-70°C to -90°C) until ready to ship. If a -80°C Freezer is not available:  
 
Samples can be stored short term in a -20° C freezer (non-frost free preferred) for up to one week (please 
ship out Monday-Wednesday only; Canada: Monday-Tuesday only). 
 
OR: 
 
Samples can be stored in plenty of Dry Ice for up to one week, replenishing daily (please ship out Monday-
Wednesday only; Canada: Monday-Tuesday only). 
 
Please indicate on Specimen Transmittal Form the storage conditions used and time stored. 
 
Shipping/Mailing: 
 
Ship specimens on Dry Ice overnight Monday-Wednesday (Monday-Tuesday from Canada) to prevent thawing 
due to delivery delays.  Saturday and holiday deliveries cannot be accepted.  
 
Include all NRG Oncology paperwork in a sealed plastic bag and tape to the outside top of the Styrofoam box. 
 
Place sealed specimen bags into the Styrofoam cooler and fill with plenty of dry ice (7-10 lbs/3.5kg minimum). Add 
padding to avoid the dry ice from breaking the tubes.  
 
Place Styrofoam coolers into outer cardboard box, and attach shipping label and UN3373 and UN1895 stickers to 
outer cardboard box. 
 
Multiple cases may be shipped in the same cooler, but make sure each one is in a separate bag and that there is 
enough room for plenty of dry ice. Add padding to avoid the dry ice from breaking the tubes. 
 
Samples received thawed will be discarded, and a notification will be sent immediately to the Principal Investigator 
and Clinical Research Assistant of the submitting institution. The institution should send a subsequent sample, 
collected as close as possible to the original planned collection date. 
 
For questions regarding ordering, collection, or shipping of a Urine Collection Kit, please e-mail 
NRGBB@ucsf.edu or call (415)476-7864 or fax (415) 476-5271. 
 
 


53  
RTOG 0926; version date February 01, 2019 
 
 
APPENDIX VI (continued) 
NRG ONCOLOGY URINE COLLECTION KIT INSTRUCTIONS 
 
 
Shipping Address: FedEx/UPS/Courier address (For all frozen samples) 
NRG Oncology Biospecimen Bank – San Francisco 
2340 Sutter Street, Room S341, San Francisco, CA  94115 Contact Phone: (415) 476-7864 

ICF_001.pdf: 
NRG ONCOLOGY 
Radiation Therapy Oncology Group 
 
RTOG 0926 
 
(ClinicalTrials.gov NCT #: 00981656) 
 
 
A Phase II Protocol for Patients with Stage T1 Bladder Cancer to Evaluate 
Selective Bladder Preserving Treatment by Radiation Therapy Concurrent 
with Radiosensitizing Chemotherapy Following a Thorough Transurethral 
Surgical Re-Staging 
 
 
Amendment 5:  February 1, 2019 


Sample consent form version: February 1, 2019 
To be attached to protocol version:  February 1, 2019 
1 
 
RTOG 0926 
 
Informed Consent Template for Cancer Treatment Trials  
(English Language) 
A Phase II Protocol For Patients With Stage T1 Bladder Cancer To Evaluate 
Selective Bladder Preserving Treatment By Radiation Therapy Concurrent With 
Radiosensitizing Chemotherapy Following A Thorough Transurethral Surgical Re-
Staging 
 
This is a clinical trial, a type of research study. Your study doctor will explain the clinical trial to you. 
Clinical trials include only people who choose to take part. Please take your time to make your decision 
about taking part. You may discuss your decision with your friends and family. You can also discuss it 
with your health care team. If you have any questions, you can ask your study doctor for more 
explanation.  
 
You are being asked to take part in this study because you have bladder cancer that has not responded 
to standard treatment. 
  
 
Why is this study being done? (3/31/14)(3/6/2015) 
 
For patients with your type of bladder cancer (non-muscle invading tumor or tumors with at least one 
being a Stage T1 tumor) for whom standard treatment (such as BCG therapy) was not successful or for 
whom BCG treatment is judged unsuitable, the usual next step for treatment in patients that are medically 
fit and accept this treatment is removal of the bladder (cystectomy). However, recently there have been 
reports that indicate a good success rate in destroying your type of bladder cancer using a repeat surgical 
procedure (transurethral resection of the bladder tumor) followed by radiation therapy plus chemotherapy. 
The majority of patients receiving this treatment did not require cystectomy and were able to maintain 
very satisfactory bladder function.  
 
The purpose of this study is to find out the effects of transurethral surgery followed by radiation therapy 
plus chemotherapy. Although the combination of radiation therapy and chemotherapy used in this study is 
not an experimental treatment because it is used for patients with more advanced bladder cancer (the 
type that has invaded the bladder muscle), the use of this approach in this study is new for patients like 
you with either a  tumor initially presenting as  a non-muscle invading stage T1  tumor that has recurred 
within 18 months of receiving BCG therapy  or with a stage Ta tumor treated by BCG therapy but recurred 
within 18 months as a T1 tumor. 
 
How many people will take part in the study? 
 
About 37 people will take part in this study  
 
What will happen if I take part in this research study? (4/6/12)(5/15/12) 
If you take part in this study, you will have a surgical procedure called a transurethral bladder resection. 
Under sedation (anesthesia), a lighted tube (fiberoptic scope) is inserted through the urethra (the small 
tube-like structure that allows urine to empty from the bladder) into the bladder. The surgeon examines 
your bladder tumor through this fiberoptic scope. The surgeon then will remove your tumor as thoroughly 
as is safely possible using an electric current. Some of your tissue around the tumor also will be removed 
(biopsy). 
 


Sample consent form version: February 1, 2019 
To be attached to protocol version:  February 1, 2019 
2 
 
Before you begin the study:  
You will need to have the following exams, tests or procedures to find out if you can be in the study.  
These exams, tests or procedures are part of the regular evaluation of your cancer and are usually done 
even if you do not join the study. If you have had some of them recently, they may not need to be 
repeated.  This will be up to your study doctor. 
• 
History and physical exam, including an assessment of your ability to carry out activities 
of daily living 
• 
Blood tests 
• 
Pregnancy test for women who are able to have children 
• 
Transurethral bladder tumor resection (TURBT; surgical removal of the tumor)  
 
If the exams, tests and procedures show that you can be in the study, and you choose to take part, then 
you will need the following tests and procedures. They are part of regular cancer care.  
• 
Cystoscopic evaluation (cystoscopy: examination of the inside of the bladder using an 
instrument called a cystoscope) 
• 
Blood tests 
• 
Bone scan if necessary 
• 
CT scan of your abdomen and pelvis: A CT scan is a test using x-rays to look at one part 
of your body 
• 
An intravenous pyelogram (IVP) if necessary: An x-ray that provides pictures of the 
kidneys, bladder, the tubes that carry urine from the kidneys to the bladder [ureters], and 
the urinary tract [urethra]. 
• 
Chest x-ray  
• 
You will be asked to fill out a questionnaire on urinary symptoms and function. 
 
There are two types of chemotherapy that may be used in this study.  Some patients will receive 
chemotherapy with a drug called cisplatin.  In some instances, your doctor will decide to treat you instead 
with two chemotherapy drugs called mitomycin and 5FU. 
 
If your treatment includes cisplatin, you will receive radiation therapy once a day, 5 days a week for about 
7 weeks. During the first 3 days of week 1, week 3 and week 5, you will also be given chemotherapy 
(cisplatin) by vein. 
  
If your treatment instead includes mitomycin and 5FU, you will still receive radiation therapy once a day, 5 
days a week for about 7 weeks. On the first day of week 1, you will receive a single treatment with mitomycin 
chemotherapy by vein. In addition, during week 1 and week 4 of chemotherapy, you will receive a 
continuous infusion of the 5FU chemotherapy through a pump. This pump will be attached to an intravenous 
line (such as a PICC line or portacath) that you will have placed before starting treatment. You do not have 
to be in the hospital during this time, but you will have to come to the clinic on the first and last days of 
those two weeks (weeks 1 and 4) to have the pump attached and then detached. If you have any problems 
with the pump during the week, you should call the office of your treating physician right away.  
 
Regardless of which chemotherapy you receive, you will need the following assessments during radiation 
therapy plus chemotherapy: 
•  Weekly measurement of your weight 
•   Weekly blood tests 
•   On your last day of treatment: an assessment of your ability to carry out activities of daily 
living  
    
When you are finished radiation and chemotherapy*: 
You will need these tests and procedures 8-10 weeks after the completion of radiation and chemotherapy 
• Cystoscopy (examination of the inside of the bladder using an instrument called a 
cystoscope) 
• Bladder biopsy 


Sample consent form version: February 1, 2019 
To be attached to protocol version:  February 1, 2019 
3 
 
• Urine cytology (a series of tests that are done to identify all the different types of cells and 
other substances in your urine) 
• *For patients in whom the tumor has not completely disappeared, surgical removal of the 
bladder or possibly further treatment by instilling drugs into your bladder, as recommended 
by your doctor   
 
You will need these tests and procedures during follow-up after the completion of radiation and 
chemotherapy 
• History and physical exam, including an assessment of your ability to carry out activities of 
daily living, blood tests, cystoscopy (for patients who still have their bladder), urine cytology, 
and bladder biopsy every 3 months after all treatment for the first year, every 4 months during 
the 2nd year, every 6 months during years 3, 4, and 5, then once a year thereafter 
• CT scan and chest x-ray once a year for years 1, 2, and 3 
• You will be asked to fill out a questionnaire on urinary symptoms and function during year 3 
After you’ve finished radiation and chemotherapy, if your tumor comes back (recurrence) your doctor may 
recommend other treatment options (for example, cystectomy – the surgical removal of your bladder). The 
type of treatment recommended will vary based on the type of tumor you have. 
 
Study Plan (4/6/12)(5/15/12) 
Another way to find out what will happen to you during the study is to read the chart below.  Start reading 
at the top and read down the list, following the lines and arrows.  
 
                                            
 
 
                                                                    
 
 
 
 
   
 
                                 
                        
 
 
 
 
           
 
 
 
 
Radiation Therapy 
Once a day, 5 days/week for about 7 weeks 
(34 treatments) 
plus  
Chemotherapy by vein  
EITHER cisplatin  
The first 3 days of weeks 1, 3, and 5 of radiation therapy 
(total of 9 infusions) 
 
OR mitomycin/5FU  
Mitomycin on week 1, day 1 and 5FU given continuously during weeks 1 and 4 
Re-examination of the bladder 
8-10 weeks after completion of radiation plus chemotherapy 
Transurethral Bladder Resection 
(surgical removal of the tumor) 
If tumor has completely disappeared 
 
Follow-up visits every 3 months for the first 
year after treatment, every 4 months for year 
2, every 6 months for years 3, 4, and 5, and 
then once a year 
If tumor has not completely disappeared  
or if it comes back 
 
Transurethral resection or 
surgical removal of bladder (if fit for surgery)  
 


Sample consent form version: February 1, 2019 
To be attached to protocol version:  February 1, 2019 
4 
 
How long will I be in the study? (4/20/15) 
Radiotherapy and chemotherapy will begin within 15 weeks after the transurethral bladder resection and 
will take 6 to 8 weeks to complete.  
 
Eight to 10 weeks after the completion of the radiation and chemotherapy, the study doctor will re-
examine your bladder. If your tumor has completely disappeared, you will be seen during follow-up visits 
every 3 months after completion of treatment for the first year, every 4 months during the 2nd year, every 
6 months for years 3, 4, and 5, then once a year thereafter. If your tumor has not completely disappeared 
or if it comes back (recurrence) and you are medically fit for surgery, surgical removal of your bladder will 
be recommended at this time. 
 
Can I stop being in the study? 
 
Yes. You can decide to stop at any time.  Tell the study doctor if you are thinking about stopping or 
decide to stop.  He or she will tell you how to stop safely.  
 
It is important to tell the study doctor if you are thinking about stopping so any risks from the radiation and 
chemotherapy (cisplatin) can be evaluated by him/her.  Another reason to tell your study doctor that you 
are thinking about stopping is to discuss what follow-up care and testing could be most helpful for you. 
 
The study doctor may stop you from taking part in this study at any time if he/she believes it is in your 
best interest, if you do not follow the study rules, or if the study is stopped. 
 
What side effects or risks can I expect from being in the study? (4/6/12)(3/6/2015) 
 
You may have side effects while on the study.  Everyone taking part in the study will be watched carefully 
for any side effects.  However, researchers don’t know all the side effects that may happen.  Side effects 
may be mild or very serious. Your health care team may give you medicines to help lessen side effects. 
Many side effects go away soon after you stop radiation and chemotherapy. In some cases, side effects 
can be serious, long lasting, or may never go away.   
 
You should talk to your study doctor about any side effects that you have while taking part in the study.    
 
Risks and side effects related to the radiation therapy to the pelvis in this study include those 
which are: 
 
COMMON, SOME MAY BE SERIOUS 
In 100 people receiving pelvis radiation, more than 20 and up to 100 may have: 
• Hair loss in the treatment area, may be permanent 
• Diarrhea   
• Need to urinate often 
• Urgency with urination 
• Slower urinary flow 
• Tiredness  
• Pain, including with urination and/or bowel movements 
• Nausea, vomiting 
• Painful sexual intercourse (women) 
• Abnormal sexual function, may be permanent (men) 
 


Sample consent form version: February 1, 2019 
To be attached to protocol version:  February 1, 2019 
5 
 
 
OCCASIONAL, SOME MAY BE SERIOUS 
In 100 people receiving pelvis radiation, from 4 to 20 may have: 
• Chronic bowel/bladder symptoms as described above 
• Blood in urine 
• Inability to control urine, inability to control bowel movements 
• Mucous-like stools 
• Bleeding of the rectum 
• Swelling, redness, rash, skin changes, or itching in the area of radiation 
 
 
 
RARE, AND SERIOUS 
In 100 people receiving pelvis radiation, 3 or fewer may have: 
• Weight loss  
• Blockage of internal organs that may require surgery  
• A tear or hole in internal organs that may require surgery 
• Bladder shrinkage, discomfort, or bleeding which may require medication or surgery, 
including removal of the bladder.  
• Internal bleeding which may cause bleeding of the rectum, black tarry stool, blood in 
vomit, blood in urine, and may require surgery. 
• Infection which may cause painful and frequent urination  
• A new cancer resulting from treatment of earlier cancer 
 
 
 
 
Radiation to the pelvis will cause sterility (inability to father children or become pregnant). 
Women of childbearing potential will go through menopause and may require the use of 
hormones given orally to replace the hormones normally produced by the ovaries. 
 
 
Risks and side effects related to chemotherapy include: 
 
 
Possible Side Effects of Cisplatin (Table Version Date: May 28, 2013) 
 
COMMON, SOME MAY BE SERIOUS 
In 100 people receiving Cisplatin, more than 20 and up to 100 may have: 
• Nausea, vomiting 
• Infection, especially when white blood cell count is low 
• Anemia which may cause tiredness, or may require blood transfusions 
• Bruising, bleeding 
• Kidney damage which may cause swelling, may require dialysis 
• Hearing loss including ringing in ears 


Sample consent form version: February 1, 2019 
To be attached to protocol version:  February 1, 2019 
6 
 
 
 
OCCASIONAL, SOME MAY BE SERIOUS 
In 100 people receiving Cisplatin, from 4 to 20 may have: 
• Allergic reaction which may cause rash, low blood pressure, wheezing, shortness of 
breath, swelling of the face or throat 
• Confusion 
• Difficulty with balance 
 
 
RARE, AND SERIOUS 
In 100 people receiving Cisplatin, 3 or fewer may have: 
• Cancer of bone marrow caused by chemotherapy later in life 
• Seizure 
 
Possible Side Effects of 5-Fluorouracil (Table Version Date: October 24, 2013) 
 
COMMON, SOME MAY BE SERIOUS 
In 100 people receiving 5-Fluorouracil, more than 20 and up to 100 may have: 
• Hair loss 
• Redness, pain or peeling of palms and soles 
• Rash, increased risk of sunburn, itching 
• Diarrhea, nausea, vomiting, loss of appetite 
• Difficulty swallowing 
• Sores in mouth 
• Heartburn 
• Headache 
 
 
OCCASIONAL, SOME MAY BE SERIOUS 
In 100 people receiving 5-Fluorouracil, from 4 to 20 may have: 
• Chest pain 
• Blood clot 
• Belly pain 
• Internal bleeding which may cause black tarry stools 
• Infection, especially when white blood cell count is low 
• Anemia which may require blood transfusions 
• Cough, hoarseness 
• Bruising, bleeding 
• Allergic reaction which may cause rash, low blood pressure, wheezing, shortness of 
breath, swelling of the face or throat 
• Confusion 
• Abnormal eye movement, blurred vision, watering eyes 
• Discomfort from light 


Sample consent form version: February 1, 2019 
To be attached to protocol version:  February 1, 2019 
7 
 
OCCASIONAL, SOME MAY BE SERIOUS 
In 100 people receiving 5-Fluorouracil, from 4 to 20 may have: 
• Swelling, redness, tingling and pain of hands and feet 
• Difficulty with balancing 
 
RARE, AND SERIOUS 
In 100 people receiving 5-Fluorouracil, 3 or fewer may have: 
• Damage to the heart which may cause shortness of breath 
• A new cancer resulting from treatment of earlier cancer 
 
 
 
Possible Side Effects of Mitomycin (Table Version Date: May 28, 2013) 
COMMON, SOME MAY BE SERIOUS 
In 100 people receiving Mitomycin, more than 20 and up to 100 may have: 
• Infection, particularly when white blood cell counts are low 
• Anemia which might require blood transfusion 
• Tiredness 
• Nausea, vomiting, diarrhea 
• Swelling of the body 
• Difficult, painful or frequent urination (when the drug is administered into the bladder) 
 
OCCASIONAL, SOME MAY BE SERIOUS 
In 100 people receiving Mitomycin, from 4 to 20 may have: 
• Loss of appetite 
• Sores in the mouth 
• Rash 
• Hair loss 
• Loss of fertility 
 
RARE, AND SERIOUS 
In 100 people receiving Mitomycin, 3 or fewer may have: 
• Scarring of the lungs 
• Kidney failure that could require treatment with dialysis 
 
 
 
Risks of Surgery:  
If removal of your bladder is necessary 
In men, after radiation, the operation generally includes removal of the bladder, the pelvic lymph nodes, 
the seminal vesicles, and the prostate.  As a result, there is likely to be loss of sexual function. In women, 
the operation may include removal of the bladder, vagina, uterus, tubes, and ovaries.  As a result, women 
may not be able to have children and may find intercourse difficult. Also during surgery, a urinary 
diversion procedure is necessary; this probably will include placement of a permanent opening (stoma) 
created in the abdomen and a bag placed over it to collect the urine.  In some circumstances other types 
of urinary diversion may be possible, based on the judgment of your surgeon. 


Sample consent form version: February 1, 2019 
To be attached to protocol version:  February 1, 2019 
8 
 
 
In general, there is a higher risk of complications for you when surgery follows radiation and 
chemotherapy.  Surgery and bladder reconstruction can be more difficult and the choices for bladder 
reconstruction are limited. In addition, if chemotherapy fails to decrease the size of the tumor, your cancer 
can be more advanced at the time of surgery. 
 
After bladder removal, the major complications that can occur include infection, heart attack, stroke, 
severe bleeding, blood clots in the legs or the lung and injury to the rectum or other areas of the intestine. 
This type of injury may require a second temporary stoma to allow the intestine to heal. Injury to the 
intestine may also lead to abnormal connections (fistulas) between the intestines and other organs.  
Minor complications include wound infection and delayed hospital stay due to intestinal inactivity (ileus).  
  
Reproductive Risks:  You should not become pregnant or father a baby while on this study because the 
drugs in this study can affect an unborn baby.  Women should not breastfeed a baby while on this study.  
It is important you understand that you need to use birth control while on this study.  Check with your 
study doctor about what kind of birth control methods to use and how long to use them.  Some methods 
might not be approved for use in this study.  
 
Radiation to the pelvis will cause sterility (inability to father children or become pregnant). Women of 
childbearing potential will go through menopause and may require the use of hormones given orally to 
replace the hormones normally produced by the ovaries. 
 
For more information about risks and side effects, ask your study doctor. 
 
Are there benefits to taking part in the study? (3/31/14) 
 
Taking part in this study may or may not make your health better. While researchers hope that radiation 
plus chemotherapy will remove all the cancer in your bladder so that surgical removal of the bladder itself 
(cystectomy) is not necessary, there is no guarantee that a cystectomy will not need to be done. 
 
One of the risks of undergoing the radiation plus chemotherapy in this study is that if a cystectomy is 
needed, the radiation plus chemotherapy might make the surgery more difficult and make it less likely that 
the surgeon would judge it safely possible to carry out all aspects of the procedure without needing to 
create a permanent opening in the abdomen (a type of “urinary diversion” procedure).   
 
We do know that information from this study will help us learn more about the advantages of the 
treatment used in the study and will help researchers learn more about the use of radiation and 
chemotherapy for patients with this type of bladder cancer. This information could help future cancer 
patients who have non-muscle invading bladder cancer. 
 
What other choices do I have if I do not take part in this study? (3/31/14)(3/6/2015) 
 
Your other choices may include: 
• 
Removal of the bladder (radical cystectomy) and a urinary diversion procedure. This is the 
standard approach for patients with non-muscle invading tumor or tumors with at least one being 
Stage T1 who have failed BCG therapy within 18 months of this treatment with a Ta or a T1 tumor 
and those patients who may have failed other forms of injection of drugs into their bladder, or 
patients who were initially diagnosed with a T1 tumor but who were unsuited to receive BCG 
therapy. 
• 
Newer forms of intravesical (within the bladder) chemotherapy with previously untested and non 
standard drugs as part of another study 
• 
Radiation therapy alone 
• 
Receiving no additional treatment other than repeat transurethral resections (with this choice, 
your tumor could continue to grow and your disease could spread) 
 


Sample consent form version: February 1, 2019 
To be attached to protocol version:  February 1, 2019 
9 
 
Talk to your study doctor about your choices before you decide if you will take part in this study. 
 
Will my medical information be kept private? (4/6/12) (3/31/14) 
 
Data are housed at NRG Oncology Statistics and Data Management Center in a password-protected 
database.  We will do our best to make sure that the personal information in your medical record will be 
kept private.  However, we cannot guarantee total privacy.  Your personal information may be given out if 
required by law.  If information from this study is published or presented at scientific meetings, your name 
and other personal information will not be used.  
 
Organizations that may look at and/or copy your medical records for research, quality assurance, and 
data analysis include: 
• 
NRG Oncology 
• 
The National Cancer Institute (NCI) and other government agencies, like the Food and Drug 
Administration (FDA), involved in keeping research safe for people 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by 
U.S. Law. This web site will not include information that can identify you. At most, the Web site 
will include a summary of the results. You can search this Web site at any time. 
 
[Note to Informed Consent Authors: the above paragraph complies with the new FDA regulation found at 
21 CFR 50.25(c) and must be included verbatim in all informed consent documents. The text in this 
paragraph cannot be revised.] 
 
What are the costs of taking part in this study? (3/31/14) 
 
You and/or your health plan/insurance company will need to pay for some or all of the costs of treating 
your cancer in this study.  Some health plans will not pay these costs for people taking part in studies.  
Check with your health plan or insurance company to find out what they will pay for.  Taking part in this 
study may or may not cost your insurance company more than the cost of getting regular cancer 
treatment.  
 
You will not be paid for taking part in this study. 
 
For more information on clinical trials and insurance coverage, you can visit the National Cancer 
Institute’s Web site at http://cancer.gov/clinicaltrials/understanding/insurance-coverage.   
 
What happens if I am injured because I took part in this study? 
 
It is important that you tell your study doctor, __________________ [investigator’s name(s)], if you feel 
that you have been injured because of taking part in this study.  You can tell the study doctor in person or 
call him/her at __________________ [telephone number]. 
 
You will get medical treatment if you are injured as a result of taking part in this study.  You and/or your 
health plan will be charged for this treatment.   The study will not pay for medical treatment.   
   
 
What are my rights if I take part in this study? (3/6/2015) 
 
Taking part in this study is your choice.  You may choose either to take part or not to take part in the 
study.  If you decide to take part in this study, you may leave the study at any time.   No matter what 
decision you make, there will be no penalty to you and you will not lose any of your regular benefits.  


Sample consent form version: February 1, 2019 
To be attached to protocol version:  February 1, 2019 
10 
 
Leaving the study will not affect your medical care.  You can still get your medical care from our 
institution.    
 
We will tell you about new information or changes in the study that may affect your health or your 
willingness to continue in the study. 
 
A Data Safety Monitoring Board will be regularly meeting to monitor safety and other data related to 
phase I, I/II, and II NRG Oncology clinical trials. The Board members may receive confidential patient 
information, but they will not receive your name or other information that would allow them to identify you 
by name. 
 
In the case of injury resulting from this study, you do not lose any of your legal rights to seek payment by 
signing this form.   
 
 
 
 
 
Who can answer my questions about the study? 
 
You can talk to your study doctor about any questions or concerns you have about this study.  Contact 
your study doctor __________________ [name(s)] at __________________ [telephone number]. 
 
 
For questions about your rights while taking part in this study, call the ________________________ 
[name of center] Institutional Review Board (a group of people who review the research to protect your 
rights) at __________________ (telephone number).  [Note to Local Investigator: Contact information for 
patient representatives or other individuals in a local institution who are not on the IRB or research team 
but take calls regarding clinical trial questions can be listed here.]    
 
 *You may also call the Operations Office of the NCI Central Institutional Review Board (CIRB) at 888-
657-3711 (from the continental US only).   [*Only applies to sites using the CIRB.] 
 
Please note:  This section of the informed consent form is about additional research that is being 
done with people who are taking part in the main study.   You may take part in this additional 
research if you want to.  You can still be a part of the main study even if you say ‘no’ to taking part 
in this additional research. 
 
You can say “yes” or “no” to [each of] the following study[ies]. Below, please mark your choice [for each 
study].   
 
Consent Form for Use of Tissue, Blood, and Urine for Research 
About Using Tissue, Blood, and Urine for Research (4/20/15) 
You have had or you will have a biopsy (or surgery) to see if you have cancer. Your doctor will remove 
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. You may also have two additional biopsies. 
 
We would like to keep some of the tissue from the biopsies for future research. If you agree, this tissue 
will be kept and may be used in research to learn more about cancer and other diseases.  
 


Sample consent form version: February 1, 2019 
To be attached to protocol version:  February 1, 2019 
11 
 
In addition, if you agree to participate in this part of the study, you will have blood drawn and urine 
collected before you start chemoradiation therapy. We would like to keep about 2 tablespoons of blood 
and 5 tablespoons of urine at this time for future research. If you agree, this blood and urine will be kept 
to be used in research to learn more about cancer and other diseases. 
 
Your tissue, blood, and urine may be helpful for research whether you do or do not have cancer. The 
research that may be done with your tissue, blood, and urine 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 tissue, blood, and urine 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 tissue, blood, and urine for future research is up to you. No matter 
what you decide to do, it will not affect your care or your participation in the main part of the study.  
 
If you decide now that your tissue, blood, and urine 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 tissue, blood, and urine. 
Then any tissue that remains will no longer be used for research and will be returned to the institution that 
submitted it. Any remaining blood and/or urine will be destroyed.  
 
In the future, people who do research may need to know more about your health. While the study doctor/ 
institution may give them reports about your health, they will not give them your name, address, phone 
number, or any other information that will let the researchers know who you are.  
 
Sometimes tissue, blood, and urine are used for genetic research (about diseases that are passed on in 
families). Even if your tissue, blood, and urine are used for this kind of research, the results will not be put 
in your health records.  
 
Your tissue, blood, and urine will be used only for research and will not be sold. The research done with 
your tissue, blood, and urine may help to develop new treatments for cancer and other diseases in the 
future.  
 
Benefits  
 
 
The benefits of research using tissue, blood, and urine 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.  
 
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. 


Sample consent form version: February 1, 2019 
To be attached to protocol version:  February 1, 2019 
12 
 
1. My specimens may be kept for use in research to learn about, prevent, or treat cancer, as follows: 
• Tissue Yes  No 
• Blood 
Yes  No 
• Urine 
Yes  No 
 
2. My specimens may be kept for use in research to learn about, prevent, or treat other health 
problems (for example: diabetes, Alzheimer's disease, or heart disease), as follows:  
• Tissue Yes  No 
• Blood 
Yes  No 
• Urine 
Yes  No 
 
 
3. Someone may contact me in the future to ask me to take part in more research.  
                    Yes  No 
 
Where can I get more information? (4/6/12) 
 
You may call the National Cancer Institute's Cancer Information Service at:  
 
1-800-4-CANCER (1-800-422-6237) 
 
You may also visit the NCI Web site at http://cancer.gov/ 
 
• 
For NCI’s clinical trials information, go to: http://cancer.gov/clinicaltrials/ 
 
• 
For NCI’s general information about cancer, go to http://cancer.gov/cancerinfo/ 
 
 
You will get a copy of this form.    If you want more information about this study, ask your study doctor. 
 
Signature 
 
I have been given a copy of all _____ [insert total of number of pages] pages of this form.  I have read it 
or it has been read to me.  I understand the information and have had my questions answered.  I agree to 
take part in this study. 
 
Participant ________________________________ 
 
Date _____________________________________