A Randomized Phase II Study of Perioperative mFOLFIRINOX Versus Gemcitabine/Nab-Paclitaxel as Therapy for Resectable Pancreatic Adenocarcinoma
Phase: PHASE2
Conditions: Pancreatic Adenocarcinoma, Resectable Pancreatic Carcinoma
Sponsor: SWOG Cancer Research Network

 
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PRIVILEGED COMMUNICATION 
Activation Date October 12, 2015 
FOR INVESTIGATIONAL USE ONLY 
 
SWOG 
 
TITLE 
A RANDOMIZED PHASE II STUDY OF PERIOPERATIVE mFOLFIRINOX VERSUS 
GEMCITABINE/NAB-PACLITAXEL AS THERAPY FOR RESECTABLE PANCREATIC 
ADENOCARCINOMA 
 
NCT #02562716 
 
 
STUDY CHAIRS: 
AGENTS: 
 
Davendra P.S. Sohal, M.D., M.P.H. (Medical 
IND-Exempt Agents: 
Cleveland Clinic Oncology) 
Fluorouracil (5-FU, Adrucil®) (NSC-19893)  
9500 Euclid Ave – R35  
Gemcitabine hydrochloride (Gemzar®) 
Cleveland, OH 44195 
 
(NSC-613327) 
Phone: 216/444-8258 
Irinotecan (Camptosar®) (NSC-616348) 
FAX: 216/444-9464 
nab-Paclitaxel (NSC-736631) 
E-mail: sohald@ccf.org   
Oxaliplatin (Eloxatin) (NSC-266046) 
 
 
Syed Ahmad, M.D. (Surgery)  
BIOSTATISTICIANS: 
University of Cincinnati Medical Center 
 
231 Albert Sabin Way, ML #0558 
Katherine A. Guthrie, Ph.D.  
Cincinnati, OH 45267 
Danika Lew, M.S. 
Phone: 513/558-7866 
SWOG Statistical Center 
FAX: 513/584-0459 
Fred Hutchinson Cancer Research Center 
E-mail: ahmadsy@uc.edu   
1100 Fairview Avenue N, M3-C102 
 
P.O. Box 19024 
Namita Gandhi, M.D. (Radiology) 
Seattle, WA  98109-1024 
Cleveland Clinic 
Phone: 206/667-4623 
9500 Euclid Ave 
FAX: 206/667-4408 
Cleveland, OH 44195 
E-mail: kguthrie@fredhutch.org   
Phone: 216/444-3682 
E-mail dlew@fredhutch.org  
FAX: 216/636-1699 
E-mail: gandhin@ccf.org  
 
 
 
Philip A. Philip, M.D., Ph.D., F.R.C.P.  
 
Karmanos Cancer Center (Medical Oncology) 
 
Wayne State University 
 
4100 John R Street 4HWCRC 
 
Detroit, MI 48201 
 
Phone: 313/576-8728 
 
FAX:313/576-8729 
 
E-Mail: philipp@karmanos.org   
 
 
 
Andrew M. Lowy, M.D., F.A.C.S. (Surgery) 
 
University of California, San Diego 
 
Moores Cancer Center 
 
3855 Health Sciences Dr., #0987 
 
La Jolla, CA 92093 
 
Phone: 858/822-2124 
 
FAX: 858/534-4813 
 
E-mail: alowy@ucsd.edu  
 
 

 
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NCTN INVESTIGATORS: 
 
Andrea Wang-Gillam M.D., Ph.D. (ALLIANCE) 
Washington University in St. Louis 
Phone: 314-362-5740 
Fax: 314-362-7086 
E-mail: awang@dom.wustl.edu   
 
M. Shaalan Beg, M.D. (ECOG-ACRIN) 
UT Southwestern Medical Center 
Phone:  214/648-4180 
FAX:  214/648-1955 
E-mail:  muhammad.beg@utsouthwestern.edu  
 
 
 
 
 
 
 
PARTICIPANTS 
 
ALLIANCE/Alliance for Clinical Trials in Oncology 
 
ECOG-ACRIN/ECOG-ACRIN Cancer Research Group 
 
NRG/NRG Oncology 
 
SWOG/SWOG 
 
 

 
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TABLE OF CONTENTS 
 
TITLE  ......................................................................................................................................................... 1 
PARTICIPANTS ............................................................................................................................................ 2 
TABLE OF CONTENTS ............................................................................................................................... 3 
CANCER TRIALS SUPPORT UNIT (CTSU) ADDRESS AND CONTACT INFORMATION ....................... 5 
SCHEMA ....................................................................................................................................................... 6 
1.0 
OBJECTIVES .................................................................................................................................. 7 
1.1 
Primary Objectives ........................................................................................................................... 7 
1.2 
Secondary Objectives ...................................................................................................................... 7 
1.3 
Translational Objectives ................................................................................................................... 7 
2.0 
BACKGROUND ............................................................................................................................... 7 
3.0 
DRUG INFORMATION .................................................................................................................... 9 
3.1 
Fluorouracil (5-FU, Adrucil ®) (NSC-19893) .................................................................................... 9 
3.2 
Gemcitabine hydrochloride (Gemzar®) (NSC-613327) ................................................................. 11 
3.3 
Irinotecan (Camptosar®) (NSC-616348) ....................................................................................... 13 
3.4 
Nab-paclitaxel (Abraxane®) (NSC-736631) ................................................................................... 14 
3.5 
Oxaliplatin (Eloxatin®) (NSC-266046) ........................................................................................... 18 
4.0 
STAGING CRITERIA ..................................................................................................................... 20 
5.0 
ELIGIBILITY CRITERIA ................................................................................................................ 21 
5.1 
Disease Related Criteria ................................................................................................................ 21 
5.2 
Prior/Concurrent Therapy Criteria .................................................................................................. 22 
5.3 
Clinical/Laboratory Criteria ............................................................................................................. 22 
5.4 
Specimen Submission Criteria ....................................................................................................... 22 
5.5 
Regulatory Criteria ......................................................................................................................... 23 
6.0 
STRATIFICATION FACTORS ....................................................................................................... 23 
7.0 
TREATMENT PLAN ...................................................................................................................... 23 
7.1 
Pre-Medication and Concomitant Medications and Care .............................................................. 23 
7.2 
Arm 1: mFOLFIRINOX ................................................................................................................... 24 
7.3 
Arm 2: Gemcitabine/nab-Paclitaxel ................................................................................................ 24 
7.4 
Surgery ........................................................................................................................................... 24 
7.5 
Radiation ........................................................................................................................................ 27 
7.6 
Criteria for Removal from Protocol Treatment ............................................................................... 27 
7.7 
Discontinuation of Treatment ......................................................................................................... 27 
7.8 
Follow-Up Period ............................................................................................................................ 27 
8.0 
TOXICITIES TO BE MONITORED AND DOSE MODIFICATIONS .............................................. 28 
8.1 
NCI Common Terminology Criteria for Adverse Events ................................................................ 28 
8.2 
General Considerations ................................................................................................................. 28 
8.3 
Dose Modifications for Arm 1: mFOLFIRINOX .............................................................................. 28 
8.4 
Dose Modifications for Arm 2: Gemcitabine/nab-Paclitaxel ........................................................... 31 
8.5 
Dose Modification Contacts ........................................................................................................... 32 
8.6 
Adverse Event Reporting ............................................................................................................... 33 
9.0 
STUDY CALENDAR ...................................................................................................................... 34 
9.1 
Arm 1: mFOLFIRINOX ................................................................................................................... 34 
10.0 
CRITERIA FOR EVALUATION AND ENDPOINT ANALYSIS ..................................................... 37 
10.1 
Measurability of Lesions................................................................................................................. 37 
10.2 
The definitions for the resection classification that should be utilized in operative notes include: 38 
10.3 
Objective Status at Each Disease Evaluation ................................................................................ 38 
10.4 
Best Response ............................................................................................................................... 40 
10.5 
Performance Status ....................................................................................................................... 40 
10.6 
Pathologic Response ..................................................................................................................... 41 
10.7 
Loco-regional recurrence ............................................................................................................... 41 
10.8 
Distant recurrence .......................................................................................................................... 41 
10.9 
Disease-Free Survival (DFS) ......................................................................................................... 41 
10.10 
Time to Death ................................................................................................................................. 41 
11.0 
STATISTICAL CONSIDERATIONS .............................................................................................. 42 
11.1 
Accrual Goals ................................................................................................................................. 42 

 
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11.2 
Primary Analysis and Power Justification ...................................................................................... 42 
11.3 
Interim Analysis .............................................................................................................................. 42 
11.4 
Other Analyses ............................................................................................................................... 43 
11.5 
Data and Safety Monitoring ........................................................................................................... 43 
12.0 
DISCIPLINE REVIEW .................................................................................................................... 43 
12.1 
Central Imaging Review ................................................................................................................. 43 
12.2  
Surgical Review and Quality Assurance ........................................................................................ 44 
13.0 
REGISTRATION GUIDELINES ..................................................................................................... 44 
13.1 
Registration Timing ........................................................................................................................ 44 
13.2 
OPEN Registration Requirements ................................................................................................. 44 
13.3 
Registration Procedures................................................................................................................. 45 
13.4 
Exceptions to SWOG registration policies will not be permitted. ................................................... 46 
14.0 
DATA SUBMISSION SCHEDULE ................................................................................................ 46 
14.1 
Data Submission Requirement ...................................................................................................... 46 
14.2 
Master Forms ................................................................................................................................. 46 
14.3 
Data Submission Procedures ........................................................................................................ 46 
14.4 
Data Submission Overview and Timepoints .................................................................................. 47 
15.0 
SPECIAL INSTRUCTIONS............................................................................................................ 49 
15.1 
Imaging Submission for Central Review (required for patient) ...................................................... 49 
15.2 
Translational Medicine and Banking .............................................................................................. 50 
16.0 
ETHICAL AND REGULATORY CONSIDERATIONS ................................................................... 51 
16.1 
Adverse Event Reporting Requirements ........................................................................................ 52 
17.0 
BIBLIOGRAPHY ............................................................................................................................ 55 
18.0 
APPENDIX ..................................................................................................................................... 58 
18.1 
Tissue-based Translational Medicine Details: Immunologic Predictors of Therapeutic Response to 
Neoadjuvant Therapy for Pancreatic AdenocarcinomaObjectives: ............................................... 59 
18.2 
Imaging Translational Medicine Details: S1505 Radiology Correlative (Retrospective): 
Quantitative CT Measurement of Muscle and Adipose Tissue and Prognosis in Patients with 
Resectable Pancreatic Adenocarcinoma” ...................................................................................... 64 
18.3 
Instructions for the SWOG Specimen Bank ................................................................................... 70 
 

 
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CANCER TRIALS SUPPORT UNIT (CTSU) ADDRESS AND CONTACT INFORMATION 
To submit site registration 
documents: 
For patient 
enrollments: 
 
Submit study data directly to the 
Lead Cooperative Group unless 
otherwise specified in the 
protocol: 
 
CTSU Regulatory Office 
1818 Market Street, 
Suite 1100 
Philadelphia, PA19103 
 
Fax: 215-569-0206 
 
Email:  
 
CTSURegulatory@ctsu.coccg.org  
 
For more information, call the CTSU 
Help Desk at 888-823-5923 or the 
Regulatory Help Desk at 866-651-
CTSU. 
 
 
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_SYSTE
M/ or https://OPEN.ctsu.org. 
 
Contact the CTSU Help Desk with 
any OPEN-related questions at 
ctsucontact@westat.com.  
 
 
 
Data collection for this study will be 
done exclusively through Medidata 
Rave.  Please see the data 
submission section of the protocol 
for further instructions.  
 
Do not submit study data or forms to 
CTSU Data Operations. Do not copy 
the CTSU on data submissions. 
 
Other Tools and Reports: Institutions 
participating through the CTSU 
continue to have access to other 
tools and reports available on the 
SWOG Workbench. Access this by 
using your active CTEP-IAM userid 
and password at the following url: 
 
https://crawb.crab.org/TXWB/ctsulog
on.aspx  
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’ website 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.  
For patient eligibility questions contact the SWOG Data Operations Center by phone or email: 
 
206-652-2267 
giquestion@crab.org  
For treatment or toxicity related questions contact the Study PI of the Coordinating Group. 
 
For questions unrelated to patient eligibility, treatment, or data submission contact the CTSU Help 
Desk by phone or e-mail: 
 
CTSU General Information Line: 
888-823-5923 
ctsucontact@westat.com  
 
All calls and correspondence will be triaged to the appropriate CTSU representative. 
 
For detailed information on the regulatory and monitoring procedures for CTSU sites please review 
the CTSU Regulatory and Monitoring Procedures policy located on the CTSU members’ website: 
 
https://www.ctsu.org  > education and resources tab > CTSU Operations Information >CTSU Regulatory 
and Monitoring Policy  
The CTSU Web site is located at https://www.ctsu.org  
 
 
 

 
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SCHEMA 
 
 
Resectable Pancreatic Adenocarcinoma 
 
 
 
REGISTRATION & RANDOMIZATION 
 
 
 
 
 
Arm 1: mFOLFIRINOX  
 
 
Arm 2: Gemcitabine/nab-Paclitaxel 
(3 CYCLES) 
 
 
 
 
 
(3 CYCLES) 
 
 
 
RESTAGING 
 
 
 
 
 
RESTAGING 
 
 
 
NO SYSTEMIC 
SYSTEMIC 
NO SYSTEMIC  
SYSTEMIC 
PROGRESSION 
PROGRESSION  
PROGRESSION 
PROGRESSION 
 
 
 
 
SURGERY* 
OFF TREATMENT 
SURGERY* 
OFF TREATMENT 
 
 
  
   mFOLFIRINOX 
Gemcitabine/nab-Paclitaxel 
   (3 CYCLES) 
(3 CYCLES) 
 
 
 
  OFF TREATMENT 
 
 
 
 
   OFF TREATMENT 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*NOTE:  If patient is unable to undergo R0 or R1 surgical resection, he or she must be taken off 
protocol treatment (see Sections 7.4g and 7.6d). 
 

 
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1.0 
OBJECTIVES 
 
1.1 
Primary Objectives 
 
a. 
To assess 2-year overall survival in each treatment arm (mFOLFIRINOX and 
gemcitabine/nab-paclitaxel) in patients with resectable pancreatic cancer. 
 
b. 
If the stated threshold is met in one or both arms: to choose the better regimen 
with respect to 2-year overall survival. 
 
1.2 
Secondary Objectives 
 
To estimate, for all patients and within treatment arms: 
 
a. 
Frequency and severity of adverse events associated with chemotherapy in the 
perioperative setting. 
 
b. 
Proportion of patients going to surgery for resection after preoperative 
chemotherapy. 
 
c. 
Proportion of patients achieving R0 resection after preoperative chemotherapy. 
 
d. 
Overall response rate following preoperative chemotherapy, including confirmed 
and unconfirmed, complete and partial response, per RECIST 1.1. 
 
e. 
Pathologic response rates after R0 or R1 resection. 
 
f. 
Patterns of recurrence (loco-regional, distant) after R0 or R1 resection. 
 
g. 
Disease-free survival from the time of R0 or R1 resection. 
 
1.3 
Translational Objectives 
 
a. 
To evaluate the impact of chemotherapy on the immune reaction to test the 
hypothesis that chemotherapy can induce the infiltration of activated and 
functional T cells in PDAC, using S1505 banked tissue specimens (see Section 
18.1). 
 
b. 
To estimate associations of quantitative CT measurements of muscle and 
adipose tissue with clinical outcomes, using S1505 archived images (see Section 
18.2).   
 
 
2.0 
BACKGROUND 
 
Pancreatic adenocarcinoma, even when presenting as resectable disease, remains a lethal 
malignancy. An estimated 10,000 persons (~20% of ~50,000 annual cases of pancreatic 
adenocarcinoma) each year in the United States will present with resectable disease. (1,2) While 
perioperative mortality for pancreatic cancer resection has declined considerably over the last few 
decades, to less than 2% in high-volume centers, overall survival remains largely unchanged. 
(3,4) This indicates that poor outcomes are largely attributable to recurrent/metastatic disease, 
and not surgical complications. To improve outcomes, adjuvant therapy has been evaluated and 
the current standard of care is surgical resection followed by adjuvant therapy, which usually 
consists of 5-fluorouracil or gemcitabine, with or without the addition of radiation. (5,6) However, 
median overall survival with best care standards remains less than 2 years. (7) A meta-analysis 
of all randomized controlled trials for the adjuvant treatment of resected pancreatic 

 
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adenocarcinoma showed that chemotherapy with 5-fluorouracil or gemcitabine improves survival 
only modestly. (8) Therefore, there is an urgent need to improve systemic therapies. 
 
Furthermore, now there is accumulating preclinical and clinical evidence that pancreatic cancer is 
a systemic disease from the outset. (9,10) Even in margin-positive resections, three-fourths of all 
patients with recurrence have systemic relapse. (11) Autopsy series have also shown that after 
surgical resection, most patients die of systemic disease. (12,13) All these data suggest that the 
administration of more effective systemic therapy may lead to improvement in clinical outcomes. 
 
Until recently, systemic therapy options in pancreatic cancer were limited. Now, we have two 
multi-agent chemotherapy regimens that have demonstrated improved overall survival in 
metastatic pancreatic cancer. (14,15) Modified FOLFIRINOX (5-fluorouracil, irinotecan, 
oxaliplatin) improves overall survival to 11.1 months, compared with 6.8 months with gemcitabine 
alone (HR=0.57, p<0.001). (16) Toxicities were considerable; since then, more clinical experience 
with this regimen has accumulated, and the omission of 5-fluorouracil bolus and use of 
hematopoietic growth factor support has allowed mitigation of some of these toxicities without 
appreciable compromise of efficacy. (17,18,19) The other regimen is gemcitabine with nab-
paclitaxel, which achieved a median overall survival of 8.5 months in patients with metastatic 
pancreatic cancer, compared with 6.7 months with gemcitabine alone (hazard ratio [HR]=0.72, 
p<0.001). (20) Toxicities were manageable, and considerable clinical experience with this 
regimen has accumulated. (21) In addition, the objective response rates with these regimens are 
impressive – up to 31.6% with mFOLFIRINOX. (22) It should be noted that mFOLFIRINOX was 
restricted to persons 75 years or younger. These regimens now provide us the opportunity to 
improve outcomes by testing them in the curative setting. Both these regimens remain attractive 
options; however, there are no head-to-head comparisons of these two regimens in either 
advanced or localized pancreatic cancer, either ongoing or planned.  
 
The appropriate setting in which to incorporate these regimens is the next question. While the 
timing of chemotherapy does not appear to influence survival outcomes – as evidenced by 
studies of preoperative and postoperative chemotherapy in resectable breast cancer, early stage 
lung cancer, and even oligo-metastatic colorectal cancer – the ability to administer aggressive 
adjuvant systemic therapy in pancreatic cancer is limited. Even standard single-agent 
gemcitabine and 5-fluorouracil carry toxicities. (23,24) Similar evidence exists in other cancers 
where major abdominal surgery is required for curative resection – in the MAGIC study of 
perioperative chemotherapy for esophagogastric cancers, While 91% of patients completed 
preoperative therapy, only 50% of patients undergoing resection were able to complete 
postoperative therapy. (25) Therefore, the preoperative setting should allow improved delivery of 
aggressive systemic therapy with the ultimate goal of improving survival outcomes. Prior studies 
(including the ongoing ACOSOG Z5041 study) of preoperative chemotherapy or chemoradiation 
have included less active regimens, but demonstrate feasibility of this approach. (26,27) Meta-
analyses of smaller studies of preoperative therapy in resectable pancreatic cancer show 
approximately 75-90% of patients undergoing surgical resection. (28,29) In these studies, most 
patients dropped out due to progressive disease – as opposed to toxicities – which is likely 
attributable to less effective systemic therapies. Therefore, this test of effective multi-agent 
systemic chemotherapy in the preoperative setting is planned. 
 
The preoperative setting will also allow drop-out of patients with occult micro-metastatic disease 
and poor performance status – these patients are unlikely to benefit from surgical resection and 
can be therefore spared unnecessary surgery. Furthermore, if the preoperative approach is 
shown to be feasible and to provide improvement in clinical outcomes, a head-to-head 
comparison of these two regimens will allow selection of the more promising regimen, which can 
then be tested against the current standard of care – surgery followed by adjuvant therapy – in a 
definitive study. A perioperative regimen can also be a platform for the addition of new agents 
such as targeted therapies.  Finally, the preoperative platform allows testing of predictors of 
response to therapy, which are planned in a parallel translational study. 

 
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Inclusion of Women and Minorities 
 
This study was designed to include women and minorities, but was not designed to measure 
differences of intervention effects.  The anticipated accrual in the ethnicity/race and sex 
categories is shown in the table below.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3.0 
D
R
U
G
 
I
N
FORMATION 
 
Investigator Brochures  
 
For information regarding Investigator Brochures, please refer to SWOG Policy 15. 
 
For this study, all drugs are commercially available; therefore, Investigator Brochures are not 
applicable to this/these drug/s.  Information about commercial drugs is publicly available in the 
prescribing information and other resources. 
 
3.1 
Fluorouracil (5-FU, Adrucil ®) (NSC-19893)  
 
a. 
PHARMACOLOGY 
 
Mechanism of Action: Fluorouracil is a pyrimidine analog antimetabolite that 
interferes with DNA and RNA synthesis in the S phase of cell division. After 
activation, the active metabolite F-UMP is incorporated into RNA to replace uracil 
and inhibit cell growth. The active metabolite, F-dUMP, inhibits thymidylate 
synthetase and depletes thymidine triphosphate.  
 
b. 
PHARMACOKINETICS 
 
Absorption: Rapid intravenous injection of fluorouracil results in high early levels 
of drug achieved both in plasma and bone marrow with a rapid fall afterwards. 
Prolonged infusions of fluorouracil show constant levels of the drug in plasma 
and significantly less in bone marrow. 
 
DOMESTICPLANNED ENROLLMENT REPORT 
Racial 
Categories 
Ethnic Categories 
Total 
Not Hispanic or Latino 
Hispanic or Latino 
Female 
Male 
Female 
Male 
American Indian/ 
Alaska Native 
1 
1 
1 
0 
3 
Asian 
2 
3 
1 
0 
6 
Native Hawaiian 
or Other Pacific 
Islander 
1 
1 
0 
0 
2 
Black or African 
American 
7 
7 
0 
0 
14 
White 
56 
60 
4 
5 
125 
More Than One 
Race 
0 
0 
0 
0 
0 
Total 
67 
72 
6 
5 
150 

 
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1. 
Distribution: Fluorouracil distributes into tumors, intestinal mucosa, bone 
marrow, liver, third space fluids and other tissues.  Fluorouracil diffuses 
readily across the blood-brain barrier and distributes into cerebrospinal 
fluid and brain tissue. 
 
2. 
Metabolism: Fluorouracil is primarily metabolized in the liver via 
dihydropyrimidine dehydrogenase (DPD) to the active metabolites 5-
fluoroxyuridine monophosphate (F-UMP) and 5-5-fluoro-2’-deoxyuridine-
5’-O-monophosphate (F-dUMP). 
 
3. 
Elimination: The mean elimination half-life of fluorouracil from plasma is 
approximately 16 minutes, with a range of 8 to 20 minutes, and is dose 
dependent. Seven to 20% of fluorouracil is excreted unchanged in the 
urine. 
 
c. 
ADVERSE EFFECTS  
 
1. 
Possible Side Effects of Fluorouracil: 
 
Refer to the current FDA-approved package insert for the most 
comprehensive and up to date information on adverse reactions. 
 
Common (> 20%): alopecia, hand-foot syndrome, maculopapular rash, 
photosensitivity, 
pruritis, 
diarrhea, 
nausea, 
vomiting, 
anorexia, 
esophagopharyngitis, stomatitis, indigestion, headache 
 
Less common (4 to ≤ 20%): angina, coronary arteriosclerosis, 
thrombophlebitis, gastrointestinal ulcer, bleeding, anemia, leucopenia, 
agranulocytosis, pancytopenia, thrombocytopenia, cough, hoarseness, 
epistaxis, anaphylaxis, hypersensitivity reaction, confusion, nystagmus, 
visual changes, lacrimation, lacrimal duct stenosis, photophobia,  
dermatitis, acute cerebellar syndrome 
 
Rare (≤ 3%): cardiotoxicity, secondary malignancy  
 
2. 
Refer to package insert or manufacturer website for the most complete 
and up to date information on contraindications, warnings and 
precautions, and adverse reactions. 
 
3. 
Pregnancy and Lactation: Pregnancy Category D. Excretion in human 
breast milk is unknown and the manufacturer recommends against 
breastfeeding while receiving fluorouracil.  
 
4. 
Drug Interactions: Fluorouracil is a strong inhibitor of CYP2C9. Refer to 
the current FDA-approved package insert for additional information. Due 
to potential drug interactions, a complete patient medication list, 
including fluorouracil, should be screened prior to initiation of and during 
treatment with fluorouracil. See Section 8.0 Toxicities to be Monitored 
and Dosage Modifications. 
 
d. 
DOSING & ADMINISTRATION 
 
See Section 7.0 Treatment Plan 

 
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e. 
HOW SUPPLIED  
 
Fluorouracil is commercially available and drug will not be supplied.  Refer to the 
current FDA-approved package insert for the most comprehensive and up to date 
information. 
 
3.2 
Gemcitabine hydrochloride (Gemzar®) (NSC-613327) 
 
a. 
PHARMACOLOGY 
 
Mechanism 
of 
Action: 
Gemcitabine 
(2'-Deoxy-2', 
2'-difluorocytidine 
monohydrochloride), like cytarabine, is a nucleoside analog of deoxycytidine.  
This antimetabolite, a pyrimidine analog inhibiting both DNA and RNA viruses, is 
cell-cycle-specific in blocking the cells at the G1/S and is retained in human 
tumor cells for long periods.  Studies suggest that gemcitabine is activated by 
deoxycytidine kinase. Deoxycytidine has been shown to reverse the growth 
inhibitory activity of gemcitabine. 
 
b. 
PHARMACOKINETICS 
 
1. 
Distribution: Gemcitabine plasma protein binding is negligible. The 
volume of distribution is increased with the infusion length. In a 
pharmacokinetics study of patients with various solid tumors, the volume 
of distribution of gemcitabine was 50 L/m2 following infusions lasting <70 
minutes. For long infusions (70 to 285 minutes), the volume of 
distribution rose to 370 L/ m2.   
 
2. 
Metabolism: Gemcitabine is metabolized intracellularly to form active 
gemcitabine di- and tri-phosphates.  The gemcitabine di- and tri-
phosphates do not appear to circulate in plasma in measurable amounts.  
Gemcitabine is metabolized by the liver to form the inactive uracil 
derivative, 2'-deoxy-2',2'-difluorouridine (dFdU).  The inactive metabolite 
does not appear to accumulate with weekly dosing; however, it is 
excreted by the kidneys and may accumulate in patients with decreased 
renal function. 
 
3. 
Elimination:   Following a single 1,000 mg/m2/30 min [14C]-gemcitabine 
infusion, 92% to 98% of the dose was recovered within 1 week after 
gemcitabine administration.  Urinary excretion of the parent drug and the 
dFdU metabolite accounted for 99% of the excreted dose, and less than 
1% of the dose was excreted in feces.  The renal clearance of 
gemcitabine is less than 10%; therefore, the parent drug appears to be 
almost completely metabolized to the inactive dFdU. 
 
Clearance of gemcitabine is affected by age and gender and is lower in 
women and the elderly.  Differences in either clearance or volume of 
distribution based on patient characteristics or the duration of infusion 
result in changes in half-life and plasma concentrations. Studies showed 
that gemcitabine half-life for short infusions ranged from 42 to 94 
minutes, for long infusions it varied from 245 to 638 minutes, depending 
on age and gender, reflecting a greatly increased volume of distribution 
with longer infusions. The terminal phase half-life for the active 
metabolite, gemcitabine triphosphate, in mononuclear cells ranges from 
1.7-19.4 hours. 

 
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c. 
ADVERSE EFFECTS  
 
1. 
Possible Side Effects of gemcitabine:  
 
Refer to the current FDA-approved package insert for the most 
comprehensive and up to date information on adverse reactions. 
 
Adverse effects reported in >20% to 100% of subjects treated with 
gemcitabine include: flu-like symptoms, nausea, vomiting, rash, alopecia, 
infection, myelosuppressionincluding anemia, leukopenia, neutropenia, 
and thrombocytopenia, muscle weakness, hematuria, paresthesia, 
sensory neuropathy, fatigue, somnolence, hearing loss, peripheral 
edema. 
 
Adverse effects reported in 4% to 20% of subjects include: diarrhea, 
constipation, stomatitis, dyspnea, capillary leak syndrome, posterior 
reversible encephalopathy syndrome (PRES). 
 
Adverse effects reported in 3% or less of subjects include: arrhythmias, 
supraventricular arrhythmias, congestive heart failure, myocardial 
infarction, desquamation and bullous skin eruptions, gangrene, 
cerebrovascular accident, hepatic failure, adult respiratory distress 
syndrome (ARDS), anaphylaxis, renal failure, pulmonary fibrosis, 
pulmonary edema, and, Interstitial, pneumonitis. 
 
2. 
Pregnancy and Lactation: Category D. Gemcitabine may cause fetal 
harm when administered to a pregnant woman.  This agent has 
produced teratogenic effects in mice and rabbits when administered at a 
dose of < 2 mg/m2.  Adverse effects included decreased fetal viability, 
weight and morphologic defects.  There is no data on gemcitabine 
administration during human pregnancy, and it is not currently known if 
metabolites are excreted in human milk.  However, many drugs are 
excreted in human milk, and there is a potential for adverse effects in 
nursing infants.  Therefore, the use of gemcitabine should be avoided in 
pregnant or nursing women because of the potential hazard to the fetus 
or infant. 
 
3. 
Drug Interactions: Per gemcitabine package insert, no formal drug 
interaction studies have been performed to date.  When gemcitabine was 
administered with carboplatin or paclitaxel there was minimal or no effect 
on the pharmacokinetics of the studied drugs. . 
 
d. 
DOSING & ADMINISTRATION 
 
See Section 7.0 Treatment Plan  
 
e. 
HOW SUPPLIED  
 
Gemcitabine is commercially available and will not be supplied. Refer to the 
current FDA-approved package insert for the most comprehensive and up to date 
information. 

 
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3.3 
Irinotecan (Camptosar®) (NSC-616348) 
 
a. 
PHARMACOLOGY 
 
Mechanism of Action: Irinotecan and its metabolite SN-38 inhibit topoisomerase 
I. Topoisomerase I relieves torsional strain in the DNA helix during replication 
and RNA transcription by inducing single-strand breaks. By binding with the 
topoisomerase I—DNA complex, irinotecan or SN-38 prevents the relegation of 
the single-strand breaks. Irreversible DNA damage occurs when a DNA 
replication fork encounters the irinotecan or SN-38/topoisomerase I complexes 
resulting in double-strand DNA breaks. Camptothecins are highly S-phase 
specific in their activity due the requirement of DNA synthesis. 
 
b. 
PHARMACOKINETICS 
 
1. 
Absorption: N/A 
 
2. 
Distribution: Protein binding of irinotecan is 30-70%, whereas SN-38 
shows a higher protein binding of 95%. Both irinotecan and SN-38 are 
primarily bound to albumin. Volume of distribution of irinotecan is 
approximately 110-234 L/m2. 
 
3. 
Metabolism: Irinotecan is metabolized primarily in the liver by 
carboxylesterase to SN-38, and via hepatic cytochrome P450 (CYP) 3A4 
to aminopentane carboxylic acid (APC). SN-38 is conjugated to form a 
glucuronide metabolite by the enzyme UDP-glucuronosyl transferase 
1A1 (UGT1A1). Genetic polymorphisms exist in the enzyme UGT1A1, 
leading to different levels of exposure and toxicity among patients.  In 
addition, both irinotecan and SN-38 undergo plasma hydrolysis between 
their active (lactone) and inactive forms (carboxylate). Finally, a small 
amount of irinotecan is metabolized by the intestinal wall. 
 
4. 
Elimination: Approximately 10-25% of irinotecan is recovered unchanged 
in urine whereas only small amounts of SN-38 have been found. 
Clearance is approximately 13.5 L/hr/m2. In addition, irinotecan has 
approximately 25% biliary excretion. 
 
c. 
ADVERSE EFFECTS  
 
1. 
Possible side effects of irinotecan: 
 
Refer to the current FDA-approved package insert for the most 
comprehensive and up to date information on adverse reactions. 
 
Adverse effects reported in >20% to 100% of subjects treated with 
irinotecan include: diarrhea and cholinergic reaction (may be severe), 
constipation, 
nausea, 
vomiting, 
asthenia, 
infection, 
leukopenia, 
neutropenia, alopecia, anorexia, weight loss, anemia, fatigue,  fever, 
pain, dizziness, cough, dyspnea, mucositis, rash, thrombocytopenia. 
 
Adverse effects reported in 4% to 20% of subjects include: 
gastrointestinal perforation, hypersensitivity reaction, cardiovascular 
events, thromboembolic events, interstitial lung disease. 
 

 
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2. 
Pregnancy and Lactation: Pregnancy Category D. It is not known 
whether irinotecan or its derivatives are excreted in human milk. 
 
3. 
Drug Interactions: Irinotecan and its active metabolite SN-38 may be 
substrates 
for 
CYP3A4, 
CYP2B6, 
OATP1B1/SCLO1B1, 
P-
glycoprotein/ABCB1 and UGT1A1. Inducers or inhibitors may affect 
serum concentrations of irinotecan. Due to potential drug interactions, a 
complete patient medication list, including irinotecan, should be screened 
prior to initiation of and during treatment with irinotecan. Refer to the 
current FDA-approved package insert. See Section 8.0 Toxicities to be 
Monitored and Dosage Modifications. 
 
d. 
DOSING & ADMINISTRATION 
 
Dosing – See Section 7.0 Treatment Plan  
 
e. 
HOW SUPPLIED  
 
Irinotecan is commercially available and will not be supplied. Refer to the current 
FDA-approved package insert for the most comprehensive and up to date 
information. 
 
3.4 
Nab-paclitaxel (Abraxane®) (NSC-736631) 
 
a. 
PHARMACOLOGY 
 
Mechanism of action:  Nab-paclitaxel for injectable suspension (paclitaxel 
protein-bound particles for injectable suspension) is an antimicrotubule agent that 
promotes the assembly of microtubules from tubulin dimers and stabilizes 
microtubules by preventing depolymerization. This stability results in the 
inhibition of the normal dynamic reorganization of the microtubule network that is 
essential for vital interphase and mitotic cellular functions.  Paclitaxel induces 
abnormal arrays or "bundles" of microtubules throughout the cell cycle and 
multiple asters of microtubules during mitosis.  
 
NAB paclitaxel utilizes a receptor-mediated (gp60) pathway on microvessel 
endothelial cells to transport the albumin-paclitaxel complex out of the blood 
stream and into the tumor interstitium. In addition, studies have shown an 
albumin-binding protein, SPARC, is over-expressed in breast tumors and may 
play a role in the accumulation of NAB paclitaxel in breast cancer cells. It is 
suggested that once the albumin-paclitaxel complex is in the tumor interstitium, 
this complex would bind to the SPARC protein and would be rapidly internalized 
by the tumor cell. 
 
b. 
PHARMACOKINETICS 
 
1. 
Absorption: NA 
 
2. 
Distribution: nab-paclitaxel is 94% bound to plasma proteins. The agent 
exhibits a very large volume of distribution at 1741L suggesting 
extensive extravascular distribution. 
 
3. 
Metabolism: nab-paclitaxel is extensively metabolized by the CYP2C8 
enzyme of the liver. Both major and minor metabolites are produced 
through this process. 
 

 
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4. 
Elimination: Only 4% of nab-paclitaxel is recovered in the urine 
unchanged, and 20% is found in feces. Mean total clearance of the agent 
is 13-30 L/hr/m2 and mean terminal half-life is 13-27 hours. 
 
 
c. 
ADVERSE EFFECTS 
 
 
 
1. 
Possible side effects of Abraxane®: Refer to the current FDA-approved 
package insert for the most comprehensive and up to date information 
on adverse reactions. 
 
Hematologic: Neutropenia, the most important hematologic toxicity, was 
dose dependent and reversible. Among patients with metastatic breast 
cancer in the randomized trial, neutrophil counts declined below 500 
cells/mm3 (Grade 4) in 9% of the patients treated with a dose of 260 
mg/m2 compared to 22% in patients receiving paclitaxel injection at a 
dose of 175 mg/m2.  In the randomized metastatic breast cancer study, 
infectious episodes were reported in 24% of the patients treated with a 
dose of 260 mg/m2 given as a 30-minute infusion.  Oral candidiasis, 
respiratory tract infections and pneumonia were the most frequently 
reported infectious complications. Febrile neutropenia was reported in 
2% of patients in the ABRAXANE® arm and 1% of patients in the 
paclitaxel injection arm.  Thrombocytopenia was uncommon.  In the 
randomized metastatic breast cancer study, bleeding episodes were 
reported in 2% of the patients in each treatment arm. Anemia (Hb < 11 
g/dL) was observed in 33% of patients treated with ABRAXANE in the 
randomized trial and was severe (Hb < 8 g/dL) in 1% of the cases.  
Among all patients with normal baseline hemoglobin, 31% became 
anemic on study and 1% had severe anemia. 
 
Hypersensitivity Reactions (HSRs): In the randomized controlled 
metastatic breast cancer study, Grade 1 or 2 HSRs occurred on the day 
of ABRAXANE® administration and consisted dyspnea (1%) and flushing, 
hypotension, chest pain, and arrhythmia (all < 1%).  The use of 
ABRAXANE® in patients previously exhibiting hypersensitivity to 
paclitaxel injection or human albumin has not been studied. During post 
marketing surveillance, rare occurrences of severe hypersensitivity 
reactions have been reported with ABRAXANE®.  Patients who 
experience a severe hypersensitivity reaction to ABRAXANE® should not 
be rechallenged with the drug. 
 
Cardiovascular: Hypotension, during the 30-minute infusion, occurred in 
5% of patients in the randomized metastatic breast cancer trial. 
Bradycardia, during the 30-minute infusion, occurred in < 1% of patients.  
These vital sign changes most often caused no symptoms and required 
neither specific therapy nor treatment discontinuation.  Severe 
cardiovascular events possibly related to single-agent ABRAXANE® 
occurred in approximately 3% of patients in the randomized trial. These 
events included chest pain, cardiac arrest, supraventricular tachycardia, 
edema, thrombosis, pulmonary thromboembolism, pulmonary emboli, 
and hypertension. Cases of cerebrovascular attacks (strokes) and 
transient ischemic attacks have been reported rarely.  Electrocardiogram 
(ECG) abnormalities were common among patients at baseline.  ECG 
abnormalities on study did not usually result in symptoms, were not 
dose-limiting, and required no intervention. ECG abnormalities were 
noted in 60% of patients in the metastatic breast cancer randomized trial.  
Among patients with a normal ECG prior to study entry, 35% of all  
patients developed an abnormal tracing while on study.  The most 

 
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frequently reported ECG modifications were non-specific repolarization 
abnormalities, sinus bradycardia, and sinus tachycardia. 
 
Respiratory: Reports of dyspnea (12%) and cough (6%) were reported 
after treatment with ABRAXANE® in the randomized trial. Rare reports (< 
1%) of pneumothorax were reported after treatment with ABRAXANE®.  
Rare reports of interstitial pneumonia, lung fibrosis, and pulmonary 
embolism have been received as part of the continuing surveillance of 
paclitaxel injection safety and may occur following ABRAXANE® 
treatment.  Rare reports of radiation pneumonitis have been received in 
paclitaxel injection patients receiving concurrent radiotherapy.  There is 
no experience with the use of ABRAXANE® with concurrent radiotherapy.   
 
Neurologic: The frequency and severity of neurologic manifestations 
were influenced by prior and/or concomitant therapy with neurotoxic 
agents. In general, the frequency and severity of neurologic 
manifestations were dose-dependent in patients receiving single-agent 
ABRAXANE®.  In the randomized trial, sensory neuropathy was 
observed in 71% of patients (10% severe) in the ABRAXANE® arm and 
in 56% of patients (2% severe) in the paclitaxel injection arm.  The 
frequency of sensory neuropathy increased with cumulative dose. 
Sensory neuropathy was the cause of ABRAXANE discontinuation in 
7/229 (3%) patients in the randomized trial. In the randomized 
comparative study, 24 patients (10%) treated with ABRAXANE® 
developed Grade 3 peripheral neuropathy; of these patients, 14 had 
documented improvement after a median of 22 days; 10 patients 
resumed treatment at a reduced dose of ABRAXANE® and 2 
discontinued due to peripheral neuropathy.  Of the 10 patients without 
documented improvement, 4 discontinued the study due to peripheral 
neuropathy. 
 
No incidences of Grade 4 sensory neuropathies were reported in the 
clinical trial. Only one incident of motor neuropathy (grade 2) was 
observed in either arm of the controlled trial.  Cranial nerve palsies have 
been reported during post marketing surveillance of ABRAXANE®.  
Because these events have been reported during clinical practice, true 
estimates of frequency cannot be made and a causal relationship to the 
events has not been established.  Reports of autonomic neuropathy 
resulting in paralytic ileus have been received as part of the continuing 
surveillance of paclitaxel injection safety.  Ocular/visual disturbances 
occurred in 13% of all patients (n=366) treated with ABRAXANE® in 
single arm and randomized trials and 1% were severe. The severe cases 
(keratitis and blurred vision) were reported in patients in a single arm 
study who received higher doses than those recommended (300 or 375 
mg/m2). These effects generally have been reversible. However, rare 
reports in the literature of abnormal visual evoked potentials in patients 
treated with paclitaxel injection have suggested persistent optic nerve 
damage. 
 
Arthralgia/Myalgia: Forty-four percent of patients treated in the 
randomized trial experienced arthralgia/myalgia; 8% experienced severe 
symptoms.  The symptoms were usually transient, occurred two or three 
days after ABRAXANE® administration, and resolved within a few days.  
exhibits a very large volume of distribution at 1741L suggesting 
extensive extravascular distribution. 
 

 
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Metabolism: nab-paclitaxel is extensively metabolized by the CYP2C8 
enzyme of the liver. Both major and minor metabolites are produced 
through this process. 
 
Hepatic: Among patients with normal baseline liver function treated with 
ABRAXANE® in the randomized trial, 7%, 36%, and 39% had elevations 
in bilirubin, alkaline phosphatase, and AST (SGOT), respectively.  Grade 
3 or 4 elevations in GGT were reported for 14% of patients treated with 
ABRAXANE® and 10% of patients treated with paclitaxel injection in the 
randomized trial.  Rare reports of hepatic necrosis and hepatic 
encephalopathy leading to death have been received as part of the 
continuing surveillance of paclitaxel injection safety and may occur 
following ABRAXANE® treatment. 
 
Renal: Overall 11% of patients experienced creatinine elevation, 1% 
severe.  No discontinuations, dose reductions, or dose delays were 
caused by renal toxicities.   
 
Gastrointestinal (GI): Nausea/vomiting, diarrhea, and mucositis were 
reported by 33%, 27%, and 7% of ABRAXANE® treated patients in the 
randomized trial.  Rare reports of intestinal obstruction, intestinal 
perforation, pancreatitis, and ischemic colitis have been received as part 
of the continuing surveillance of paclitaxel injection safety and may occur 
following ABRAXANE® treatment.  Rare reports of neutropenic 
enterocolitis (typhlitis), despite the coadministration of G-CSF, were 
observed in patients treated with paclitaxel injection alone and in 
combination with other chemotherapeutic agents.   
 
Injection Site Reaction: Injection site reactions have occurred 
infrequently with ABRAXANE® and were mild in the randomized clinical 
trial.  Recurrence of skin reactions at a site of previous extravasation 
following administration of paclitaxel injection at a different site, i.e., 
"recall", has been reported rarely.  Rare reports of more severe events 
such as phlebitis, cellulitis, induration, skin exfoliation, necrosis, and 
fibrosis have been received as part of the continuing surveillance of 
paclitaxel injection safety.  In some cases the onset of the injection site 
reaction in paclitaxel injection patients either occurred during a prolonged 
infusion or was delayed by a week to ten days.  Given the possibility of 
extravasation, it is advisable to closely monitor the infusion site for 
possible infiltration during drug administration. 
 
Asthenia:  Asthenia was reported in 47% of patients (8% severe) treated 
with ABRAXANE® in the randomized trial.  Asthenia included reports of 
asthenia, fatigue, weakness, lethargy and malaise. 
 
2. 
Pregnancy and Lactation: 
 
Pregnancy Category D. ABRAXANE® can cause fetal harm when 
administered to a pregnant woman.  Administration of paclitaxel protein-
bound particles to rats on gestation Days 7 to 17 at doses of 6 mg/m2 
(approximately 2% of the daily maximum recommended human dose on 
a mg/m2 basis) caused embryo- and fetotoxicity, as indicated by 
intrauterine mortality, increased resorptions (up to 5-fold), reduced 
numbers of litters and live fetuses, reduction in fetal body weight and 
increase in fetal anomalies.  Fetal anomalies included soft tissue and 
skeletal malformations, such as eye bulge, folded retina, microphthalmia, 
and dilation of brain ventricles.  A lower incidence of soft tissue and 

 
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skeletal malformations were also exhibited at 3 mg/m2 (approximately 
1% of the daily maximum recommended human dose on a mg/m2 basis). 
 
There are no adequate and well-controlled studies in pregnant women 
using ABRAXANE®.  If this drug is used during pregnancy, or if the 
patient becomes pregnant while receiving this drug, the patient should be 
apprised of the potential hazard to the fetus.  Women of childbearing 
potential should be advised to avoid becoming pregnant while receiving 
treatment with ABRAXANE®. 
 
Nursing Mothers:  It is not known whether paclitaxel is excreted in human 
milk. Following intravenous administration of carbon-14 labeled paclitaxel 
to rats on days 9 to 10 postpartum, concentrations of radioactivity in milk 
were higher than in plasma and declined in parallel with the plasma 
concentrations.  Because many drugs are excreted in human milk and 
because of the potential for serious adverse reactions in nursing infants, 
it is recommended that nursing be discontinued when receiving 
ABRAXANE® therapy. 
 
3. 
Drug Interactions: 
 
Paclitaxel is metabolized by hepatic cytochrome P450 (CYP) 
isoenzymes 2C8 and 3A4 and its metabolism could be affected by 
agents inhibiting these enzymes. 
 
Due to potential drug interactions, a complete patient medication list, 
including Abraxane®, should be screened prior to initiation of and during 
treatment with Abraxane®   See Section 8.0 Toxicities to be Monitored 
and Dosage Modifications. 
 
d. 
DOSING & ADMINISTRATION 
 
See Section 7.0 Treatment Plan. 
 
e. 
HOW SUPPLIED  
 
Nab-paclitaxel is commercially available and will not be supplied. Refer to the 
current FDA-approved package insert for the most comprehensive and up to date 
information. 
 
3.5 
Oxaliplatin (Eloxatin®) (NSC-266046) 
 
a. 
PHARMACOLOGY 
 
Mechanism of Action: Oxaliplatin is a non-cell cycle specific, alkylating 
antineoplastic agent that inhibits DNA synthesis through the formation of 
crosslinks between the N7 positions of two adjacent guanines (GG), adjacent 
adenine-guanines (AG), and guanines separated by an intervening nucleotide 
(GNG). These crosslinks inhibit DNA replication and transcription. 
 
b. 
PHARMACOKINETICS 
 
1. 
Absorption: N/A 
 
Distribution: At the end of a 2-hour infusion, approximately 15% of the 
administered oxaliplatin is present in the systemic circulation. The 
remaining 85% is rapidly distributed into tissues or eliminated in the 

 
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urine. In patients, plasma protein binding of oxaliplatin is irreversible and 
greater than 90%. The main binding proteins are albumin and gamma-
globulins.  
 
2. 
Metabolism: Oxaliplatin undergoes rapid and extensive nonenzymatic 
biotransformation. There is no evidence of cytochrome P450-mediated 
metabolism in vitro. Up to 17 platinum-containing derivatives have been 
observed in plasma ultrafiltrate samples from patients, including several 
cytotoxic species and a number of noncytotoxic, conjugated species. 
 
3. 
Elimination: The major route of oxaliplatin elimination is renal excretion. 
At five days after a single 2-hour infusion, urinary elimination accounted 
for about 54% of the platinum eliminated, with fecal excretion accounting 
for only about 2%. Oxaliplatin was cleared from plasma at a rate (10 – 17 
L/h) that was similar to or exceeded the average human glomerular 
filtration rate (GFR; 7.5 L/h). There was no significant effect of gender on 
the clearance of ultrafilterable oxaliplatin. The renal clearance of 
ultrafilterable oxaliplatin is significantly correlated with GFR. 
 
c. 
ADVERSE EFFECTS  
 
1. 
Possible Side Effects of Oxaliplatin:  
 
Refer to the current FDA-approved package insert for the most 
comprehensive and up to date information on adverse reactions. 
 
Common (> 20%): anemia, diarrhea, nausea, vomiting, constipation, loss 
of 
appetite, 
fatigue, 
thrombocytopenia, 
leukopenia, 
neutropenia, 
neuropathy, paresthesia, pain, fever, cough 
 
Less common (4 to ≤ 20%): thromboembolic event, cardiac arrhythmias, 
hearing loss, dry eye/mouth/skin, conjunctivitis, visual changes (including 
loss), ascites, gastroesophageal reflux disease, flatulence, nervous 
system disorders, edema, dyspnea, bleeding, gastrointestinal ulcers, 
pulmonary toxicity, stomatitis, chills, injection site reaction, abnormal liver 
function tests, hemolytic uremic syndrome, anaphylaxis, hypersensitivity, 
dehydration, 
dizziness, 
headache, 
dysgeusia, 
rigors, 
stroke, 
pharyngolaryngeal dysesthesia, myasthenia, seizure, anxiety, confusion, 
depression, urinary frequency, rhinitis, hiccups, sinus disorders, 
pulmonary 
fibrosis, 
alopecia, 
pruritis, 
rash, 
hives, 
diaphoresis, 
hypertension, hypotension. 
 
Rare (≤ 3%): acute interstitial nephritis, hand-foot syndrome, reversible 
posterior encephalopathy syndrome 
 
2. 
Pregnancy and Lactation: Pregnancy Category D. It is not known 
whether oxaliplatin or its derivatives are excreted in human milk. 
 
3. 
Drug Interactions: No specific cytochrome P-450-based drug interaction 
studies have been conducted. Because platinum-containing species are 
eliminated primarily through the kidney, clearance of these products may 
be decreased by coadministration of potentially nephrotoxic compounds; 
although, this has not been specifically studied. Refer to the current 
FDA-approved package insert. 

 
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d. 
DOSING & ADMINISTRATION 
 
See Section 7.0 Treatment Plan  
 
e. 
HOW SUPPLIED  
 
Oxaliplatin is commercially available and will not be supplied. Refer to the current 
FDA-approved package insert for the most comprehensive and up to date 
information. 
 
 
4.0 
STAGING CRITERIA 
 
Pancreas Cancer Clinical Staging Criteria, AJCC 7th Edition, 2009 
  
DEFINITION OF TNM 
  
Primary Tumor (T) 
  
TX 
Primary tumor cannot be assessed 
T0 
No evidence of primary tumor 
Tis 
Carcinoma in situ* 
T1 
Tumor limited to the pancreas, 2 cm or less in greatest dimension 
T2 
Tumor limited to the pancreas, more than 2 cm in greatest dimension 
T3 
Tumor extends beyond the pancreas but without involvement of the celiac axis or the 
superior mesenteric artery 
  
* This also includes the “PanInIII” classification.  
  
Regional Lymph Nodes (N) 
  
NX 
Regional lymph nodes cannot be assessed 
N0  
No regional lymph node metastasis 
N1  
Regional lymph node metastasis 
  
 
 
Distant Metastasis (M) 
 
M0        No distant metastasis 
  
STAGE GROUPING 
  
Stage IA 
T1 
N0 
M0 
  
Stage IB 
T2 
N0 
M0 
  
Stage IIA 
T3 
N0  
M0 
  
Stage IIB 
T1 
N1 
M0 
 
T2 
N1 
M0 
 
T3 
N1 
M0 

 
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5.0 
ELIGIBILITY CRITERIA 
 
Each of the criteria in the following section must be met in order for a patient to be considered eligible for 
registration.  Use the spaces provided to confirm a patient's eligibility.  For each criterion requiring test 
results and dates, please record this information on the Onstudy Form and submit via Medidata Rave® 
(see Section 14.0).  Any potential eligibility issues should be addressed to the Data Operations Center in 
Seattle at 206/652-2267 prior to registration. 
 
In calculating days of tests and measurements, the day a test or measurement is done is considered Day 
0.  Therefore, if a test is done on a Monday, the Monday 4 weeks later would be considered Day 28.  This 
allows for efficient patient scheduling without exceeding the guidelines.  If Day 7, 14, 21 or 28 falls on a 
weekend or holiday, the limit may be extended to the next working day. 
 
5.1 
Disease Related Criteria 
 
a. 
Patients 
must 
have 
histologically 
or 
cytologically 
proven 
pancreatic 
adenocarcinoma. Histologies other than adenocarcinoma, or any mixed 
histologies, will NOT be eligible. 
 
b. 
Patients must have measurable disease in the pancreas as defined in Section 
10.1. CT scans or MRIs used to assess measurable disease must have been 
completed within 28 days prior to registration.  All disease must be assessed and 
documented on the Baseline Tumor Assessment Form. 
 
c. 
Patients must have resectable primary tumor based on contrast-enhanced CT or 
MRI (CT or MRI without contrast as part of PET/CT or PET/MRI is NOT 
acceptable; CT or MRI with contrast as part of PET/CT or PET/MRI is 
acceptable) of the chest, abdomen, and pelvis.  The local interpreting radiologist 
must review the scans and sign the S1505 Local Radiology Checklist prior to 
registration.  Resectable is defined as: 
 
1. 
No involvement of the celiac artery, common hepatic artery, and superior 
mesenteric artery (and, if present, replaced right hepatic artery).  
 
2. 
No involvement, or < 180° interface between tumor and vessel wall, of 
the portal vein and/or superior mesenteric vein; and patent portal 
vein/splenic vein confluence. 
 
3. 
No evidence of metastatic disease. Lymphadenopathy (defined as nodes 
measuring > 1cm in short axis) outside the surgical basin (i.e., para-
aortic, peri-caval, celiac axis, or distant nodes) is considered M1 disease 
and makes the patient ineligible. If, however, such nodes are biopsied 
and are negative, then enrollment can be considered after review with 
the study chairs. 
 
NOTE:  For tumors of the body and tail of the pancreas, involvement of the 
splenic artery and vein of any degree is considered resectable disease. 
 
d. 
CT scans or MRIs used to assess disease at baseline must be submitted for 
central review (see Section 15.1). 
 
e. 
Patients must have surgical consult to verify patient is a surgical candidate within 
21 days prior to registration. 

 
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5.2 
Prior/Concurrent Therapy Criteria 
 
a. 
Patients must not have received prior surgery, radiation therapy, chemotherapy, 
targeted therapy, or any investigational therapy for pancreatic cancer. 
 
5.3 
Clinical/Laboratory Criteria 
 
a. 
Patients must have a Zubrod Performance Status of 0-1 (see Section 10.5). 
 
b. 
Patients must be > 18 and < 75 years old. 
 
c. 
Patients must have adequate hematologic function as evidenced by all of the 
following within 14 days prior to registration: ANC > 1,500/mcL; platelets > 
100,000/mcL; and hemoglobin > 9 g/dL. 
 
d. 
Patients must have adequate hepatic function as evidenced by all of the following 
within 14 days prior to registration: total bilirubin < 1.5 x Institutional Upper Limit 
of Normal (IULN); AST and ALT both < 2.5 x IULN; and serum albumin > 3 g/dL. 
 
e. 
Patients must have adequate kidney function as evidenced by serum creatinine < 
IULN within 14 days prior to registration. 
 
f. 
Patients with uncontrolled intercurrent illness including, but not limited to ongoing 
or active infection, symptomatic congestive heart failure, unstable angina 
pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would 
limit compliance with study requirements will NOT be eligible. 
 
g. 
No prior malignancy is allowed except for adequately treated basal (or squamous 
cell) skin cancer, in situ cervical cancer, in situ breast (ductal or lobular) cancer, 
or other cancer for which the patient has been disease and treatment-free for two 
years. 
 
h. 
Patients must not be pregnant or nursing due to risk of fetal or nursing infant 
harm.  Women/men of reproductive potential must have agreed to use an 
effective contraceptive method for up to 3 months after the final administered 
dose of chemotherapy.  A woman is considered to be of "reproductive potential" 
if she has had menses at any time in the preceding 12 consecutive months.  In 
addition to routine contraceptive methods, "effective contraception" also includes 
heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-
effect of pregnancy prevention) defined as a hysterectomy, bilateral 
oophorectomy or bilateral tubal ligation.  However, if at any point a previously 
celibate patient chooses to become heterosexually active during the time period 
for use of contraceptive measures outlined in the protocol, he/she is responsible 
for beginning contraceptive measures. 
 
i. 
CA19-9 must be performed within 14 days prior to registration. 
 
j. 
Prestudy history and physical must be obtained within 28 days prior to 
registration. 
 
5.4 
Specimen Submission Criteria 
 
a. 
Sites must seek additional patient consent for the future use of specimens as 
described in Section 15.2. 

 
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5.5 
Regulatory Criteria 
 
a. 
Patients must be informed of the investigational nature of this study and must 
sign and give written informed consent in accordance with institutional and 
federal guidelines. 
 
b. 
As a part of the OPEN registration process (see Section 13.2 for OPEN access 
instructions) the treating institution's identity is provided in order to ensure that 
the current (within 365 days) date of institutional review board approval for this 
study has been entered in the system. 
 
 
6.0 
STRATIFICATION FACTORS 
 
Patients will be stratified according to Zubrod Performance Status:  0 vs. 1. 
 
 
7.0 
TREATMENT PLAN 
 
For treatment or dose modification questions, please contact Dr. Sohal at 216/444-8258 or Dr. 
Ahmad at 513/558-7866. For dosing principles or questions, please consult the SWOG Policy #38 
"Dosing Principles for Patients on Clinical Trials" at http://swog.org (then click on "Policies and 
Manuals" under the "Visitors" menu and choose Policy 38). 
 
7.1 
Pre-Medication and Concomitant Medications and Care 
 
a. 
Pre-Medication and Concomitant Medications 
 
Pre-medications and concomitant medicines will be administered to counter the 
expected common side-effects of chemotherapy. These may include anti-emetic, 
anti-allergy, and anti-diarrheal medicine. These will be ordered by the treating 
physician per institutional standards and tailored to the patient’s condition. 
 
Appropriate anti-emetics include, but are not limited to, corticosteroids, 5-HT3 
antagonists (ondansetron, palonosetron), and NK1 antagonists (aprepitant, 
fosaprepitant). Further intravenous medicines and fluids may also be used per 
the treating physician’s recommendations. Oral medicines can be prescribed for 
use at home, as deemed appropriate by the treating physician. These may 
include anti-emetics, analgesics, anti-pyretics, anti-diarrheals, pancreatic enzyme 
supplements, appetite stimulants, antacids, H2-blockers, proton pump inhibitors, 
anxiolytics, anti-depressants, sleep aids, and other common medicines as 
needed. Referral to health care providers from other specialties, such as 
palliative medicine, nutrition, psychology, psychiatry, home care services, etc., 
may be made as needed per the patient’s clinical situation. 
 
b. 
Management of Biliary Obstruction 
 
Patients with biliary obstruction, either at baseline or during the study period, may 
continue on the protocol treatment as long as all parameters for treatment are 
met. Biliary obstruction may be managed by biliary stents or drains per treating 
physician’s discretion. 

 
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7.2 
Arm 1: mFOLFIRINOX 
 
Patients on Arm 1: mFOLFIRINOX will receive 3 cycles of the following treatment, 
surgery, and 3 additional cycles of the following treatment: 
 
Agent 
Dose 
Route 
Day 
Schedule* 
 
Oxaliplatin  
85 mg/m2  
IV over 2 hours  
1, 15 
Prior to irinotecan 
 
Irinotecan  
180 mg/m2  
IV over 1.5 hours  
1, 15 
Following oxaliplatin 
 
5-FU 
 
2,400 mg/m2  
IV over 46 hours   
1-3, 15-17 
Following oxaliplatin  
 
 
  
 
 
 
and irinotecan 
 
*  Note: One cycle = 28 days 
** 5-fluorouracil will be administered as a continuous intravenous infusion delivered by 
an infusion pump via a central venous infusion port placed subcutaneously. The 
specific chemotherapy port and infusion pump to be used are at the discretion of the 
treating physician. 
 
Following the initial 3 cycles of mFOLFIRINOX treatment, patients will undergo restaging 
by contrast-enhanced CT or MRI. Patients with stable disease or better will undergo 
surgery for resection 4 to 8 weeks following completion of initial chemotherapy (see 
Section 7.4). Within 4 to 8 weeks following resection, patients will begin an additional 3 
cycles of mFOLFIRINOX treatment. 
 
7.3 
Arm 2: Gemcitabine/nab-Paclitaxel 
 
Patients on Arm 2: Gemcitabine/nab-Paclitaxel will receive 3 cycles of the following 
treatment, surgery, and an additional 3 cycles of the following treatments: 
 
AGENT 
DOSE 
ROUTE 
DAY 
 
SCHEDULE* 
 
nab-Paclitaxel 
125 mg/m2 
IV over 30 min 
1, 8, 15 
Prior to gemcitabine 
 
Gemcitabine 
1,000 mg/m2 
IV over 30 min 
1, 8, 15 
Following nab-paclitaxel 
 
*  Note: One cycle = 28 days 
** A central venous infusion port placed subcutaneously for the delivery of chemotherapy 
is allowed, but not required, in Arm 2.  
 
Following the initial 3 cycles of gemcitabine/nab-paclitaxel treatment, patients will 
undergo restaging by CT or MRI. Patients with stable disease or better will undergo 
surgery for resection 4 to 8 weeks following completion of initial chemotherapy (see 
Section 7.4). Within 4 to 8 weeks following resection, patients will begin an additional 3 
cycles of gemcitabine/nab-paclitaxel treatment. 
 
7.4 
Surgery 
 
a. 
General Considerations  
 
Pancreatectomy should occur within 4 to 8 weeks after the last dose of Cycle 3 
preoperative chemotherapy. Staging laparoscopy may be performed at the time 
of planned laparotomy but is not required. Either standard or pylorus-preserving 
pancreaticoduodenectomy, 
distal 
subtotal 
pancreatectomy, 
or 
total 
pancreatectomy may be performed. Surgical drains and enteral tubes (e.g. 

 
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gastrostomy and/or jejunostomy tubes) may be placed at the discretion of the 
operating surgeon.  
 
Patients who are unable to complete 3 cycles of chemotherapy prior to surgery 
may continue to surgery, if patient is still resectable and a surgical candidate. 
Patient will then receive Cycles 4-6 with appropriate dose modification. 
 
b. 
Specific Considerations  
 
Exploration of the peritoneal cavity should include evaluation for radiologically 
occult macroscopic peritoneal or hepatic metastases. Biopsy proof of liver or 
peritoneal metastatic disease (by frozen section assessment) should be 
considered criteria for abandoning planned pancreatectomy.  
 
Lymph node sampling or frozen section lymph node biopsy is not required or 
recommended as part of the intraoperative assessment for extra-pancreatic 
disease, and is at the discretion of the surgeon.  
 
For patients undergoing pancreaticoduodenectomy, the retroperitoneal dissection 
along the medial edge of the uncinate process and the right lateral border of the 
superior mesenteric artery is believed to be an important oncologic part of the 
operation. All soft tissue to the right of the superior mesenteric artery (SMA) 
should be removed. This requires exposure and dissection along the right lateral 
border of the SMA. 
 
Vascular resection and/or reconstruction of the superior mesenteric vein, portal 
vein, SMV/ Portal vein confluence, or hepatic artery will be done at the discretion 
of the operating surgeon.  In general, vascular resection should be performed 
when necessary to achieve a R0 resection.  This reconstruction can be 
performed by the operating surgeon or a vascular surgeon consult.  The details 
of this operation should be delineated in the operative report.   
 
c. 
Intraoperative Frozen Section Assessment of Surgical Margins  
 
Frozen section evaluation of the pancreatic parenchymal should be performed. 
When a pancreaticoduodenectomy is performed, frozen section of the hepatic (or 
bile) duct margins should also be performed. In the event of a positive frozen 
section margin at either of these loci, further resection in an effort to achieve 
microscopically negative margins should be performed if possible. For patients 
undergoing pancreaticoduodenectomy, the superior mesenteric arterial (SMA) 
margin should be evaluated on permanent section only.  
 
d. 
Specimen Orientation for Surgical Pathology  
 
The surgeon should ensure that the specimen is oriented for the surgical 
pathologist. Any segment of resected vascular structure (e.g. superior mesenteric 
or portal vein) should be identified and marked. Relevant margins evaluated by 
intraoperative frozen section (i.e. the hepatic (bile) duct, and pancreatic 
parenchymal) should be identified. The SMA margin (the soft tissue immediately 
adjacent to the SMA) should be separately inked using the principles outlined in 
the 2009 AJCC staging system for exocrine pancreatic cancer.  
 
Note: The SMA margin cannot be identified accurately after the specimen has 
been fixed in formalin or after the specimen has been dissected for 
histopathologic analysis. 

 
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e. 
Operative Note Dictation and Editing: Resection Classification  
 
The attending surgeon should dictate the operative note. The operative report 
should contain: 
 
1. 
A section detailing the operative findings with respect to the extent of 
disease and the primary tumor anatomy  
 
2. 
A statement as to whether or not the surgeon believes there is residual 
macroscopic tumor.  
 
The surgeon should integrate the operative findings with the microscopic surgical 
margins reported on the final pathology report in order to assign a resection 
classification prefix of R0, R1, or R2 (see Section 10.2). Whenever possible, this 
prefix should be added to the final operative note before finalizing the document. 
An example of the final procedure description for a patient who underwent 
macroscopically complete tumor removal with a positive SMA margin on 
permanent 
section 
final 
pathology 
is: 
“R1 
pylorus-preserving 
pancreaticoduodenectomy.”  
 
f. 
Surgical Pathology  
 
Pathological examination of the resected pancreatic tumor specimen should be 
carried out by a local pathologist experienced in the diagnosis of pancreatic 
adenocarcinoma.  
 
For pancreaticoduodenectomies, three primary margins (bile duct, pancreatic 
neck, and SMA) should be identified and inked by the surgeon and/or 
pathologist. Any segment of resected vascular structure (e.g. superior mesenteric 
or portal vein) should be identified and marked. The SMA margin (that tissue 
immediately adjacent to the SMA) should be separately inked according to the 
procedures and recommendations of the American Joint Commission on Cancer 
7th edition staging system and the College of American Pathologists guidelines 
for reporting of resected exocrine pancreatic cancer (2012).  The tumor should 
be thoroughly sampled (at least one section per 1 cm of greatest tumor 
dimension, taken perpendicular to the inked SMA margin). The distance between 
the closed tumor cell and the inked SMA margin should be reported. 
 
1. 
Frozen Section Assessment of Margins  
 
Section assessment of bile duct and pancreatic neck margins should be 
performed by the local pathologist in all cases as requested by the 
surgeon  
 
2. 
Permanent Section Assessments and Final Pathology Report  
 
The pathology report should contain all of the elements outlined in the 
College of American Pathologists guidelines for reporting of resected 
exocrine pancreatic cancer (2012). In particular, there should be specific 
comment on:  
• Histologic diagnosis with comment on the cell of origin (pancreatic vs. 
bile duct vs. ampulla)  
• Degree of differentiation (well, moderate, poor)  
• Total number of lymph nodes examined  
• Number of positive nodes 
• Final margins status for the bile duct, pancreatic parenchymal, and 

 
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SMA margin  
• Distance (in mm) from the tumor to the inked SMA margin  
• Extent of tumor infiltration (if present) of the blood vessel wall for any 
resected major blood vessels  
• Tumor Regression Grade (see Section 10.6) 
 
g. 
Patients with Residual Gross Disease (R2 Resections)  
 
In cases where the surgeon documents the presence of residual gross disease, 
the patient will be taken off protocol treatment. 
 
h. 
Surgical Quality Assurance 
 
See Section 12.2 for information. 
 
i. 
Credentialing 
 
This study will not require formal credentialing of the operating surgeon.  This 
study is designed for centers skilled at the multidisciplinary management of 
pancreas 
cancer. 
 
Ideally, 
centers 
should 
perform 
more 
than 
12 
pancreaticoduodenectomies per year. 
 
7.5 
Radiation 
 
Radiation is not allowed during protocol treatment. 
 
7.6 
Criteria for Removal from Protocol Treatment 
 
a. 
Completion of 3 cycles of post-surgical resection chemotherapy. 
 
b. 
Distant progression of disease prior to surgery, disease recurrence after surgery, 
or symptomatic deterioration (as defined in Section 10.3e). 
 
c. 
Unacceptable toxicity.  
 
d. 
Inability to undergo R0 or R1 surgical resection. 
 
e. 
Treatment delay for any reason > 4 weeks except protocol-defined perioperative 
treatment delays (see Section 7.2 and 7.3). 
 
f. 
Post-surgery chemotherapy delayed > 12 weeks from surgery. 
 
g. 
The patient may withdraw from the study at any time for any reason. 
 
7.7 
Discontinuation of Treatment 
 
All reasons for discontinuation of treatment must be documented in the Off Treatment 
Notice. 
 
7.8 
Follow-Up Period 
 
All patients will be followed until death or four years after registration, whichever occurs 
first. 

 
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8.0 
TOXICITIES TO BE MONITORED AND DOSE MODIFICATIONS 
 
8.1 
NCI Common Terminology Criteria for Adverse Events 
 
This study will utilize the CTCAE (NCI Common Terminology Criteria for Adverse Events) 
Version 5.0 for toxicity and Serious Adverse Event reporting.  A copy of the CTCAE 
Version 5.0 can be downloaded from the CTEP home page (http://ctep.cancer.gov).  All 
appropriate treatment areas should have access to a copy of the CTCAE Version 5.0. 
 
8.2 
General Considerations 
 
For chemotherapy doses that are held due to toxicities, they will not be “added at the 
end”. The patient will continue subsequent doses per study calendar. For example, if Day 
15 of Cycle 1 of gemcitabine/nab-paclitaxel is held, the next dose will be 14 days later, on 
Day 1 of Cycle 2, and will be counted as such. 
 
The use of marrow growth factors (including, but not limited to, filgrastim, pegfilgrastim) is 
not allowed at the outset. They can be used in case of neutropenia, per dose modification 
guidelines in Section 8.3. 
 
For post-operative chemotherapy, doses for Cycle 4 will resume at the levels for the final 
pre-operative dose, and NOT at initial dose levels. In addition, residual toxicities from pre-
operative chemotherapy will be considered. For example, if a patient continues to have a 
Grade 2 toxicity, such as neuropathy or fatigue, Cycle 4 Day 1 drugs and doses will be 
modified/held accordingly. 
 
8.3 
Dose Modifications for Arm 1: mFOLFIRINOX 
 
a. 
Dose Modifications 
 
 
Dose Reduction 
Dose Reduction 
Drug 
Initial dose 
Level 1 
Level 2 
 
 
5-FU 
2400 mg/m2 
1920 mg/m2 
1600 mg/m2 
 
Irinotecan 
180 mg/m2 
135 mg/m2 
90 mg/m2 
 
Oxaliplatin 
85 mg/m2 
65 mg/m2 
50 mg/m2  
  
 
NOTE:  Patients who require dose reductions below values listed will be removed 
from protocol treatment. 
 
b. 
Neutrophil Count Decreased 
 
For Grade 2 or higher neutropenia, hold treatment for up to two weeks until 
recovery to at least Grade 1. If patient has not recovered to ≤ Grade 1 in two 
weeks, discontinue treatment. Follow drug specific modifications below for 
subsequent cycles. In addition, it is recommended that pegfilgrastim, 6 mg 
subcutaneously, be administered with each subsequent dose, on the day of 5-FU 
pump discontinuation. 

 
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Toxicity Grade  Modification: 5-FU 
Irinotecan 
Oxaliplatin 
 
 
2 
Maintain dose 
Maintain dose 
Maintain dose 
 
3-4 
Maintain dose 
1st occurrence: 
1st occurrence: 
 
 
 
Reduce by 1 
Maintain dose 
 
 
 
 
dose level 
 
 
 
2nd occurrence: 
2nd occurrence: 
 
 
Reduce by 1 
Reduce by 1  
 
 
Dose level 
dose level 
 
 
 
3rd occurrence: 
3rd occurrence: 
 
 
Discontinue 
Discontinue 
 
 
treatment 
treatment  
 
 
c. 
Platelet Count Decreased 
 
For Grade 2 or higher thrombocytopenia, hold treatment for up to two weeks until 
recovery to at least Grade 1. If patient has not recovered to < Grade 1 in two 
weeks, discontinue treatment. Follow drug specific modifications below for 
subsequent cycles. 
 
Toxicity Grade  
Modification: 5-FU 
Irinotecan 
Oxaliplatin 
 
 
2 
Maintain dose 
Maintain dose 
Maintain dose 
 
3-4 
1st occurrence: 
1st occurrence: 
1st occurrence: 
 
Reduce by 1 
Maintain dose 
Reduce by 1 
 
dose level 
 
dose level  
 
 
2nd occurrence: 
2nd occurrence: 
2nd occurrence: 
 
 
Reduce by 1 
Reduce by 1 
Reduce by 1  
 
dose level 
dose level 
dose level 
 
 
3rd occurrence: 
3rd occurrence: 
3rd occurrence: 
 
Discontinue 
Discontinue 
Discontinue 
 
treatment 
treatment 
treatment 
 
 
 
d. 
Diarrhea 
 
Patients should be instructed in the use of loperamide as treatment for diarrhea. 
Patient should not be retreated with irinotecan until recovery from diarrhea has 
occurred.  
 
Toxicity Grade   
Modification 
 
 
3-4 
1st occurrence: Reduce irinotecan by 1 dose level and 5-
FU dose by 1 dose level. 
 
 
2nd occurrence: Reduce irinotecan by 1 dose level, 
oxaliplatin dose by 1 dose level, and 5-FU dose by 1 
dose level. 
 
 
3rd occurrence: Discontinue all protocol treatment 
 
 

 
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e. 
Mucositis 
 
 
 
Toxicity Grade   
Modification 
 
 
 
Oxaliplatin 
 
5-FU 
 
2 
Hold treatment.  
Hold treatment. 
 
Check weekly.  
Check weekly. 
 
When resolves to 
When resolves to 
 
≤ Grade 1, continue 
≤ Grade 1, continue  
 
 
 
at same dose level. 
at next lowest dose level. 
 
3-4  
Hold treatment.  
Hold treatment. 
 
Check weekly.  
Check weekly. 
 
When resolves to 
When resolves to 
 
≤ Grade 1, continue 
≤ Grade 1, continue at  
 
 
 
 
at same dose level. 
next lowest dose level. 
 
 
f. 
Paresthesia or Peripheral Sensory Neuropathy – Dose modifications for 
oxaliplatin only 
 
 
 
 
 
Duration of Toxicity 
 
Persistent between 
Toxicity Grade   
1 – 7 days 
> 7 days 
cycles 
 
 
2 
 
 
No dose 
No dose 
Next lowest dose 
 
 
 
modification 
modification 
level for oxaliplatin 
 
3 
 
 
Next lowest 
Next lowest 
Discontinue 
 
 
 
dose level 
dose level 
 
 
 
for oxaliplatin 
for oxaliplatin 
 
Peripheral Sensory 
Discontinue 
Discontinue 
Discontinue 
Neuropathy Grade 4 
 
 
g. 
Hand-Foot Skin Reaction 
 
Toxicity Grade  
Modification: 
 
 
 
3-4 
Reduce 5-FU by 1 dose level  
 
 
 
h. 
Other non-hematologic toxicities 
 
All treatment related non-hematological toxicities (with the exception of hair loss) 
should resolve to Grade 1 prior to starting next cycle of therapy.  
 
Toxicity Grade  
Modification: 5-FU, Irinotecan, and Oxaliplatin 
 
 
3 
Hold all drugs until resolution to < Grade 1. Then resume 
treatment at the next lower dose level. 
 
4 
Discontinue all protocol treatment 
 
 

 
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8.4 
Dose Modifications for Arm 2: Gemcitabine/nab-Paclitaxel 
 
a. 
Dose Modifications 
 
 
 
Dose Reduction 
Dose Reduction 
Drug 
Initial dose 
Level 1 
Level 2 
 
 
Gemcitabine 
1000 mg/m2 
800 mg/m2 
650 mg/m2 
 
nab-Paclitaxel 
125 mg/m2 
100 mg/m2 
80 mg/m2 
 
NOTE:  Patients who require dose reductions below the values listed will be 
removed from protocol treatment. 
 
b. 
Neutrophil Count Decreased 
 
For Grade 2 or higher neutropenia, hold treatment for up to two weeks until 
recovery to at least Grade 1. If patient has not recovered to ≤ Grade 1 in two 
weeks, discontinue treatment. Follow drug specific modifications below for 
subsequent cycles. In addition, it is recommended that pegfilgrastim, 6 mg 
subcutaneously, be administered with each subsequent Day 15 dose of 
gemcitabine/nab-paclitaxel. 
 
Toxicity Grade   
Modification 
 
 
 
Gemcitabine 
nab-Paclitaxel 
 
2 
Maintain Dose 
Maintain dose 
 
3-4 
1st occurrence reduce 
1st occurrence reduce 
 
dose by 1 level. 
dose by1 level. 
 
 
2nd occurrence reduce 
2nd occurrence reduce 
 
dose by 1 level. 
dose by 1 level. 
 
 
3rd occurrence discontinue 
3rd occurrence discontinue 
 
 
c. 
Platelet Count Decreased 
 
For Grade 2 or higher thrombocytopenia, hold treatment for up to two weeks until 
recovery to at least Grade 1. If patient has not recovered to ≤ Grade 1 in two 
weeks, discontinue treatment. Follow drug specific modifications below for 
subsequent cycles. 

 
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Toxicity Grade   
Modification 
 
 
 
Gemcitabine 
 
nab-Paclitaxel 
 
2 
Maintain dose  
Maintain dose 
 
3-4 
1st occurrence  
1st occurrence 
 
reduce dose by  
reduce dose by 
 
1 level.  
 
1 level. 
 
 
2nd occurrence  
2nd occurrence 
 
reduce dose by  
reduce dose by 
 
1 level.  
 
1 level. 
 
3rd occurrence  
3rd occurrence 
 
discontinue 
 
discontinue 
 
 
d. 
Peripheral Sensory Neuropathy – Dose modifications for nab-Paclitaxel only 
 
 
 
 
 
Duration of Toxicity 
 
Persistent between 
Toxicity Grade   
1 – 7 days 
> 7 days 
cycles 
 
 
2 
 
 
No dose 
No dose 
Next lowest dose 
 
 
 
modification 
modification 
level for nab-paclitaxel 
 
3 
 
 
Next lowest 
Next lowest 
Discontinue 
 
 
 
dose level 
dose level 
 
 
 
for  
 
for 
nab-paclitaxel nab-paclitaxel 
 
Peripheral Sensory 
Discontinue 
Discontinue 
Discontinue 
Neuropathy Grade 4 
 
 
 
e. 
Non-hematologic toxicities 
 
All treatment related non-hematological toxicities (with the exception of hair loss) 
should resolve to ≤ Grade 1 prior to starting next cycle of therapy.  
 
Toxicity Grade  
Modification: Gemcitabine, nab-Paclitaxel. 
 
 
3 
Hold all drugs until resolution to < Grade 1. Then resume 
treatment at the next lower dose level. 
 
4 
Discontinue all protocol treatment 
 
 
 
8.5 
Dose Modification Contacts 
 
For treatment or dose modification questions, please contact Dr. Sohal at 216/444-8258 
or Dr. Ahmad at 513/558-7866, or Dr. Philip at 313/576-8728. 

 
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8.6 
Adverse Event Reporting 
 
Toxicities (including suspected reactions) that meet the expedited reporting criteria as 
outlined in Section 16.0 of the protocol must be reported to the Operations Office, Study 
Chair and NCI via CTEP-AERS, and to the IRB per local IRB requirements. 
 

 
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9.0 
STUDY CALENDAR 
 
9.1 
Arm 1: mFOLFIRINOX 
REQUIRED STUDIES 
Pre-
study 
Cycle 1 
Cycle 2 
Cycle 3 
 
F/U after 
Chemo- 
Re-
staging 
 
Surgery 
Cycle 
4 
Cycle  
5 
Cycle  
6 
F/U 
prior to 
prog  
or 
recur-
rence 
F/U 
after 
prog 
or 
recur-
rence 
 
D 
1 
D 
15 
D 
1 
D 
15 
D 
1 
D 
15 
D 
1 
£ 
D 
15 
D 
1 
D 
15 
D 
1 
D 
15 
PHYSICAL 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
H&P Exam  ⌂ 
X 
X 
X 
X 
X 
X 
X 
X Ω 
 
X 
X 
X 
X 
X 
X 
X 
X 
Weight and Performance Status 
⌂ 
X 
X 
X 
X 
X 
X 
X 
X Ω 
 
X 
X 
X 
X 
X 
X 
 
 
Toxicity Assessment ⌂ 
 
 
X 
X 
X 
X 
X 
X Ω 
 
 
X 
X 
X 
X 
X 
 
 
Surgical Complications Ə 
 
 
 
 
 
 
 
 
 
X Ə 
 
 
 
 
 
 
 
LABORATORY 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CBC  † ⌂ 
X 
X 
X 
X 
X 
X 
X 
X Ω 
 
X 
X 
X 
X 
X 
X 
 
 
Comprehensive Metabolic 
Panel δ 
X 
 
 
 
 
 
 
X Ω 
 
 
 
 
 
 
 
 
 
CA19-9 
X 
 
 
 
 
 
 
X Ω 
 
 
 
 
 
 
 
X 
 
AST and ALT 
X 
 
 
 
 
 
 
X Ω 
 
 
 
 
 
 
 
 
 
Serum albumin 
X 
 
 
 
 
 
 
X Ω 
 
 
 
 
 
 
 
 
 
Serum creatinine  
X 
 
 
 
 
 
 
X Ω 
 
 
 
 
 
 
 
 
 
SCANS 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CT or MRI for disease 
assessment ¿ 
X ʐ 
 
 
 
 
 
 
X Ω 
 
 
 
 
 
 
 
X ∑ 
 
SPECIMEN SUBMISSION 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tissue from surgical resection √ 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
TREATMENT 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Oxaliplatin 
 
X 
X 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
 
 
Irinotecan 
 
X 
X 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
 
 
5-FU § 
 
X 
X 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
 
 
Surgery 
 
 
 
 
 
 
 
 
X µ 
 
 
 
 
 
 
 
 
Note:  1 cycle = 28 days.  
NOTE: Unless indicated otherwise in the protocol, scheduled procedures and assessments (treatment administration, toxicity assessment for 
continuous treatment, disease assessment, specimen collection and follow-up activities) must follow the established SWOG guidelines as 
outlined in https://swog.org/Visitors/Download/QA/Best%20Practices%20upddate.pdf. 
Click here for footnotes: 

 
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9.2 
Arm 2: Gemcitabine/nab-Paclitaxel 
 
REQUIRED STUDIES 
PRESTUDY 
Cycle 1 
Cycle 2 
Cycle 3 
 
F/U after 
Chemo/ 
Restaging 
 
Surgery 
Cycle 4 
4  £ 
Cycle 
5 
Cycle 
6 
 
F/U  
prior 
to 
prog 
or 
recur 
 
F/U  
after  
prog 
or 
recur 
D 
1 
D 
8 
D 
15 
D 
1 
D 
8 
D 
15 
D 
1 
D 
8 
D 
15 
D 
1 
D 
8 
 
D 
15 
 
D 
1 
D 
8 
D 
15 
D 
1 
D 
8 
D 
15 
PHYSICAL 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
History & Physical Exam  ⌂ 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X Ω 
 
X 
 
X 
X 
 
X 
X 
 
X 
X 
X 
Wt; Perform. Status ⌂ 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X Ω 
 
X 
 
X 
X 
 
X 
X 
 
X 
 
 
Toxicity Assessment ⌂ 
 
 
 
X 
X 
 
X 
X 
 
X 
X Ω 
 
 
 
X 
X 
 
X 
X 
 
X 
 
 
Surgical Complications Ə 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Ə 
 
 
 
 
 
 
 
 
 
 
LABORATORY 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CBC  † * 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X Ω 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Comprehensive Metabolic  
Panel δ 
X 
 
 
 
 
 
 
 
 
 
X Ω 
 
 
 
 
 
 
 
 
 
 
 
 
CA19-9 
X 
 
 
 
 
 
 
 
 
 
X Ω 
 
 
 
 
 
 
 
 
 
 
X 
 
AST & ALT 
X 
 
 
 
 
 
 
 
 
 
X Ω 
 
 
 
 
 
 
 
 
 
 
 
 
Serum albumin 
X 
 
 
 
 
 
 
 
 
 
X Ω 
 
 
 
 
 
 
 
 
 
 
 
 
Serum creatinine  
X 
 
 
 
 
 
 
 
 
 
X Ω 
 
 
 
 
 
 
 
 
 
 
 
 
SCANS 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CT or MRI for disease 
assessment  ¿ 
X 
ʐ 
 
 
 
 
 
 
 
 
 
X Ω 
 
 
 
 
 
 
 
 
 
 
X ∑ 
 
SPECIMEN SUBMISSION 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tissue from surgical 
resection √ 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
TREATMENT 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
nab-Paclitaxel ◊ 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Gemcitabine  
hydrochloride  ◊ 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Surgery 
 
 
 
 
 
 
 
 
 
 
 
X µ 
 
 
 
 
 
 
 
 
 
 
 
Note:  1 cycle = 28 days 
NOTE: Unless indicated otherwise in the protocol, scheduled procedures and assessments (treatment administration, toxicity assessment for 
continuous treatment, disease assessment, specimen collection and follow-up activities) must follow the established SWOG guidelines as outlined 
in https://swog.org/Visitors/Download/QA/Best%20Practices%20upddate.pdf. 
Click here for footnotes: 

 
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Footnotes for Arm 1 and Arm 2 Calendars: 
 
α Follow-up performed every 3 months for Year 1, every 6 months for Years 2 and 3, then annually until four years from registration. 
† Hemoglobin, WBC, platelet count, and ANC. 
δ  Sodium, potassium, bicarbonate, chloride, BUN, calcium, total protein, total bilirubin, and alkaline phosphatase. 
Ω Within 2-4 weeks following last dose of chemotherapy in Cycle 3. 
µ Within 4-8 weeks following last dose of chemotherapy in Cycle 3. 
£ Cycle 4 chemotherapy should start within 4-8 weeks following surgery. If patient is unable to begin chemotherapy within 12 weeks after 
resection, patient must be taken off protocol treatment. 
√ See Section 15.2 for information. 
ʐ Submit scans as outlined in Section 14.0 and Section 15.0. 
Ə Assess for surgical complications at this visit. 
§ 5-FU treatment will occur on Days 1-3 and 15-17 of each cycle. 
¿ CT or MRI must include chest, abdomen, and pelvis. Restaging scans must be done within 4 weeks following last dose of chemotherapy 
(whether chemotherapy was completed or not). 
∑ The first scan following completion of Cycle 6 must be performed within 2 weeks. 
⌂ Assessment must be performed on Days 1 and 15 of each cycle. For Cycle 1, assessment does not need to be performed on Day 1. 
◊ Treatment on Days 1, 8, and 15 of each cycle.  No treatment on Day 22 (see Section 7.3). 
* CBC must be performed on Day 1, 8, and 15 of each cycle of treatment for patients on Arm 2. 
 
 
 
 
 

 
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10.0 
CRITERIA FOR EVALUATION AND ENDPOINT ANALYSIS 
 
This study will use the RECIST 1.1 guidelines. (30) 
 
10.1 
Measurability of Lesions 
 
a. 
Measurable disease 
 
Measurable disease is defined differently for lymph nodes compared with other 
disease and will be addressed in a separate section below. 
 
b. 
Measurable disease  
 
 
Measurable disease is defined differently for lymph nodes compared with other 
disease and will be addressed in a separate section below. 
 
1. 
Lesions that can be accurately measured in at least one dimension 
(longest diameter to be recorded) as ≥ 2.0 cm by chest x-ray, by ≥ 1.0 
cm with CT or MRI scans, or ≥ 1.0 cm with calipers by clinical exam. All 
tumor measurements must be recorded in decimal fractions of 
centimeters (or millimeters). 
 
The defined measurability of lesions on CT scan is based on the 
assumption that CT slice thickness is 0.5 cm or less.  If CT scans have 
slice thickness greater than 0.5 cm, the minimum size for a measurable 
lesion should be twice the slice thickness.   
 
2. 
Malignant lymph nodes are to be considered pathologically enlarged and 
measurable if it measures ≥ 1.5 cm in SHORT AXIS (greatest diameter 
perpendicular to the long axis of the lymph node) when assessed by 
scan (CT scan slice recommended being no greater than 0.5 cm). 
 
c. 
Non-measurable disease:  All other lesions (or sites of disease), including small 
lesions (longest diameter < 1.0 cm or pathologic lymph nodes with ≥ 1.0 cm to < 
1.5 cm short axis), are considered non-measurable disease.  Bone lesions, 
leptomeningeal disease, ascites, pleural/pericardial effusions, lymphangitis 
cutis/pulmonitis, inflammatory breast disease, and abdominal masses (not 
followed by CT or MRI), are considered non-measurable as are previously 
radiated lesions that have not progressed. 
 
d. 
Notes on measurability 
 
1. 
For CT and MRIs, the same type of scanner should be used and the 
image acquisition protocol should be followed as closely as possible to 
prior scans.  Body scans should by performed with breath-hold scanning 
techniques, if possible.  
 
2. 
PET-CT:  At present, the low dose or attenuation correction CT portion of 
a PET-CT is not always of optimal diagnostic CT quality for use with 
RECIST measurements.  However, if the site can document that the CT 
performed as part of a PET-CT is of identical diagnostic quality to a 
diagnostic CT, then the CT portion of the PET-CT can be used for 
RECIST measurements and can be used interchangeably with 
conventional CT. 
 

 
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3. 
Ultrasound: Ultrasound is not useful in assessment of lesion size and 
should not be used as a method of measurement. 
 
4. 
Cystic lesions that meet the criteria for radiographically defined simple 
cysts should not be considered as malignant lesions (neither measurable 
nor non-measurable) since they are, by definition simple cysts. 
 
5. 
If a target lesion becomes very small some radiologists indicate that it is 
too small to measure.  If the lesion is actually still present, a default 
measurement of 0.5 cm should be applied.  If the radiologist believes the 
lesion has gone, a default measurement of 0.0cm should be recorded. 
 
10.2 
The definitions for the resection classification that should be utilized in operative notes 
include:  
 
• 
R0 – macroscopically complete tumor removal with negative microscopic surgical 
margins (bile duct, pancreatic parenchyma, and SMA margins)  
• 
R1 – macroscopically complete tumor removal with any positive microscopic surgical 
margin (bile duct, pancreatic parenchyma, or SMA margins)  
• 
R2 – macroscopically incomplete tumor removal with known or suspected residual 
gross disease  
 
10.3 
Objective Status at Each Disease Evaluation   
 
Objective Status is to be recorded at each evaluation. All measurable lesions up to a 
maximum of 2 lesions per organ 5 lesions in total, representative of all involved organs, 
should be identified as target lesions at baseline. All other lesions (or sites of disease) 
including any measurable lesions over and above the 5 target lesions should be identified 
as non-target lesions.  Measurements must be provided for target measurable lesions, 
while presence or absence must be noted for non-target measurable and non-
measurable disease.   
 
For studies that use disease progression as an endpoint, whole body scanning at specific 
intervals is necessary to determine that progression is NOT present outside of the 
“target” areas. Therefore, in these studies it is not acceptable to image only the “target” 
areas of the body in follow-up scans. For study-specific imaging requirements, see the 
Study Calendar in Section 9.0.   
 
a. 
Complete Response (CR):  Complete disappearance of all target and non-
target lesions (with the exception of lymph nodes mentioned below).  No new 
lesions.  No disease related symptoms.  Any lymph nodes (whether target or 
non-target) must have reduction in short axis to < 1.0 cm.  All disease must be 
assessed using the same technique as baseline. 
 
b. 
Partial Response (PR): Applies only to patients with at least one measurable 
lesion. Greater than or equal to 30% decrease under baseline of the sum of 
appropriate diameters of all target measurable lesions.  No unequivocal 
progression of non-measurable disease.  No new lesions.  All target measurable 
lesions must be assessed using the same techniques as baseline. 
 
c. 
Stable: Does not qualify for CR, PR, Progression or Symptomatic Deterioration.  
All target measurable lesions must be assessed using the same techniques as 
baseline. 
 
d. 
Progression: One or more of the following must occur:  20% increase in the sum 
of appropriate diameters of target measurable lesions over smallest sum 
observed (over baseline if no decrease during therapy) using the same 

 
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techniques as baseline, as well as an absolute increase of at least 0.5 cm.  
Unequivocal progression of non-measurable disease in the opinion of the treating 
physician (an explanation must be provided).  Appearance of any new lesion/site.  
Death due to disease without prior documentation of progression and without 
symptomatic deterioration (see Section 10.3e). 
 
Notes regarding new lesions:  FDG-PET imaging can complement regular scans 
in identifying new lesions according to the following algorithm.  
 
1. 
Negative FDG-PET at baseline, with a positive FDG-PET at follow-up is 
a sign of progression based on a new lesion. 
 
2. 
No FDG-PET at baseline and a positive FDG-PET at follow-up 
corresponding to a potential new site of disease must have a 
confirmation by anatomical assessment (e.g. CT, MRI, x-ray) as new site 
of disease to be considered progressive disease.  In such a case, the 
date of progressive disease will be the date of the initial abnormal FDG-
PET.   
 
e. 
Symptomatic deterioration:  Global deterioration of health status requiring 
discontinuation of treatment without objective evidence of progression.  Efforts 
should be made to obtain objective evidence of progression after discontinuation. 
 
f. 
Assessment inadequate, objective status unknown.  Progression or 
symptomatic deterioration has not been documented, and one or more target 
measurable lesions have not been assessed or inconsistent assessment 
methods were used. 
 
g. 
Objective status notes: 
 
1. 
Non-measurable and non-target measurable disease do not affect 
Objective Status  in determination of CR (must be absent--a patient who 
otherwise has a CR, but who has non-measurable or non-target 
measurable disease present or not assessed, will be classified as having 
a PR). However, non-measurable and non-target lesions are included in 
determination of progression (if new sites of disease develop or if 
unequivocal progression occurs in the opinion of the treating physician).  
 
2. 
An objective status of PR or stable cannot follow one of CR.  Stable can 
follow PR only in the rare case that tumor increases too little to qualify as 
progression, but enough that a previously documented 30% decrease no 
longer holds. 
 
3. 
In cases for which initial flare reaction is possible (hypercalcemia, 
increased bone pain, erythema of skin lesions), objective status is not 
progression unless either symptoms persist beyond 4 weeks or there is 
additional evidence of progression.   
 
4. 
Lesions that appear to increase in size due to presence of necrotic tissue 
will not be considered to have progressed.  
 
5. 
For bone disease documented on bone scan only, increased uptake 
does not constitute unequivocal progression. However, increase in the 
soft tissue component of a lesion as measured by CT or MRI would 
constitute progression. 
 
 

 
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6. 
Appearance of new pleural effusions does not constitute unequivocal 
progression unless cytologically proven of neoplastic origin, since some 
effusions are a toxicity related to therapy or other medical conditions. 
Increase in the size of an existing effusion does not constitute 
unequivocal progression, since the fluid status of the patient could alter 
the size of the effusion.  
 
7. 
If CR determination depends on a lesion for which the status is unclear 
by the required tests, it is recommended the residual lesion be 
investigated with biopsy or fine needle aspirate.   
 
10.4 
Best Response 
 
This is calculated from the sequence of objective statuses. 
 
a. 
CR:  Two or more objective statuses of CR a minimum of four weeks apart 
documented before progression or symptomatic deterioration. 
 
b. 
PR: Two or more objective statuses of PR or better a minimum of four weeks 
apart documented before progression or symptomatic deterioration, but not 
qualifying as CR. 
 
c. 
Unconfirmed CR:  One objective status of CR documented before progression or 
symptomatic deterioration but not qualifying as CR or PR. 
 
d. 
Unconfirmed PR:  One objective status of PR documented before progression or 
symptomatic deterioration but not qualifying as CR, PR or unconfirmed CR. 
 
e. 
Stable/no response:  At least one objective status of stable/no response 
documented at least 6 weeks after registration and before progression or 
symptomatic deterioration, but not qualifying as anything else above. 
 
f. 
Increasing disease:  Objective status of progression within 12 weeks of 
registration, not qualifying as anything else above.   
 
g. 
Symptomatic deterioration: Objective status of symptomatic deterioration within 
12 weeks of registration, not qualifying as anything else above.   
 
h. 
Inadequate assessment, response unknown:  Progression or symptomatic 
deterioration greater than 12 weeks after registration and no other response 
category applies. 
 
10.5 
Performance Status   
 
Patients will be graded according to the Zubrod Performance Status Scale. 
 
POINT 
DESCRIPTION 
 
0 
Fully active, able to carry on all pre-disease performance without 
restriction. 
 
1 
Restricted in physically strenuous activity but ambulatory and able to 
carry out work of a light or sedentary nature, e.g., light housework, 
office work. 
 
2 
Ambulatory and capable of self-care but unable to carry out any work 
activities; up and about more than 50% of waking hours.   

 
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3 
Capable of limited self-care, confined to bed or chair more than 50% of 
waking hours.   
 
4 
Completely disabled; cannot carry on any self-care; totally confined to 
bed or chair.   
 
10.6 
Pathologic Response 
 
Pathologic response will be evaluated after the patient has had surgery, and will be 
based on local pathology review of the resected surgical specimen, according to the 
following (Treatment effect per College of American Pathology Protocol for the 
Examination of Specimens From Patients With Carcinoma of the Exocrine Pancreas):  
 
Tumor Regression Grade: 
 
0: Complete response – no residual tumor 
1: Moderate response – minimal residual cancer (single cells or small groups of 
cancer cells) 
2:  Minimal response – residual cancer outgrown by fibrosis 
3: Poor or no response – no definite response identified (minimal or no tumor kill; 
extensive residual cancer) 
 
10.7 
Loco-regional recurrence 
 
Any evidence of new disease within the pancreatic tumor bed based on surveillance 
scans. The pancreatic tumor bed includes: 
 
a. 
Superior mesenteric artery and vein lymph nodes 
 
b. 
Lymph nodes in porta hepatis (bile duct, portal vein, hepatic artery lymph nodes) 
 
c. 
Lymph nodes around left renal vein, inferior vena cava or aorta 
 
d. 
Celiac axis lymph nodes 
 
10.8 
Distant recurrence 
 
Any evidence of new disease outside the primary tumor bed (liver, lungs, etc.) based on 
surveillance scans. 
 
10.9 
Disease-Free Survival (DFS) 
 
DFS is calculated for patients who undergo surgical resection (R0/R1). DFS will be 
measured from the date of surgical resection to date of first documentation of recurrence 
(loco-regional or distant) or death due to any cause. Patients last known to be alive and 
free of disease will be censored at date of last contact. 
 
10.10 
Time to Death 
 
From date of registration to date of death due to any cause.  Patients last known to be 
alive are censored at date of last contact. 
 

 
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11.0 
STATISTICAL CONSIDERATIONS 
 
11.1 
Accrual Goals 
 
Prior to temporary closure, the study was accruing approximately 6 patients per month. 
Allowing for an approximately 33% rate of ineligibility, we will accrue a total of 150 
patients to have 100 eligible patients, and thus expect an additional 12 months of accrual. 
 
11.2 
Primary Analysis and Power Justification 
 
SWOG will use a randomized Phase II “pick the winner” study design, with minimum 
activity requirements, to address the objective of choosing a chemotherapy regimen for 
further study in resectable pancreatic adenocarcinoma, since preoperative chemotherapy 
is not well-studied in this population. The goal of this design is to pick the best treatment 
regimen to carry forward into a Phase III trial in which the chosen regimen will be 
compared to the current standard approach of adjuvant chemotherapy only. Patients will 
be randomly assigned in equal proportions to the two treatment regimens. For each arm, 
the observed 2-year overall survival (OS) will first be compared to the null hypothesis of 
40%, assuming a 58% alternative hypothesis, 88% power, and a 1-sided significance of 
0.05. If rates in both arms meet this threshold, then a sample size of 100 patients (50 per 
arm) provides a 90% probability of selecting the better regimen with an OS hazard ratio 
of at least 1.4. OS will be assessed in all eligible patients according to the intent-to-treat 
principle. If only a single arm meets the 2-year OS threshold as described above, then 
that arm will be chosen to move forward; if neither arm meets this threshold then the 
overall approach will be reconsidered. 
 
11.3 
Interim Analysis 
 
Given the lack of data on peri-operative chemotherapy, we do not have a dependable 
estimate of the rate of resection in this setting. There are several small, single-institution 
phase II studies using various chemotherapy agents (usually gemcitabine or 5-
fluorouracil, with or without cisplatin) with or without radiation. These studies, and meta-
analyses of these studies, indicate that 57-74% of patients with initially resectable cancer 
are able to undergo surgical resection. (31,32,33,34) With our aggressive chemotherapy 
regimens, patients experiencing toxicity that prevents them from undergoing resection is 
a safety concern. From the pivotal studies of these regimens, it is known that Grade 3 or 
higher toxicities are common – hematologic toxicities, fatigue, nausea, vomiting, and 
diarrhea being seen in 10-40% of cases. (35,36) Our best guess, therefore, is a 10% rate 
of failure to reach resection due to toxicities from preoperative chemotherapy. The study 
will be suspended pending further review if there is sufficient evidence to suggest that the 
true probability of failing to reach surgery due to toxicity from preoperative chemotherapy 
exceeds 10% in the combined study cohort.  
 
Sufficient evidence will be taken to be an observed failure rate whose lower one-sided 
90% confidence limit exceeds the threshold. Of the first 45 evaluable patients, 3 (7%) 
failed to reach surgery due to toxicity from preoperative chemotherapy. The observed 
failure rates will be examined again after the 80th enrolled patient becomes evaluable. 
Operationally, these limits will be met if 17 failures in 80 patients are observed. Based on 
5,000 simulated datasets, and given a true failure rate of 5%, study suspension would 
occur with probability of less than 1%. Given a true failure rate of 25%, the probability of 
study suspension is 98% after 80 patients. 
 
Furthermore, we will evaluate various subsets of patients based on outcomes. There may 
be a subset of patients who go to surgery but are found to have unresectable or 
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sectional imaging modalities (CT and MRI) to detect occult peritoneal or hepatic 
metastases. Data on such patients are poor – from historical series, this number is 
expected to be at least around 10%. (37,38)  Another subset of patients may experience 
progression of disease during preoperative chemotherapy. This will be duly noted but is 
not a safety concern. In fact, an important advantage of this approach is identification of 
aggressive biology that is not responsive to the best current systemic chemotherapy 
regimens. These patients are unlikely to benefit – and may even be harmed – by surgical 
resection. We estimate ~20% of patients experiencing disease progression, based on the 
pivotal studies of these regimens. (39,40) Therefore, 1 in 3 patients may not be able to 
undergo surgical resection. 
 
11.4 
Other Analyses 
 
Secondary endpoints will include overall resection rate, R0 resection rate, pathological 
response rates, patterns of recurrence, disease-free survival (DFS), overall response rate 
per RECIST 1.1, and toxicity.  
 
With 50 patients, rates of resection and response can be estimated to within 14% (95% 
confidence interval). It is assumed that R0 resection and pathological response has not 
been achieved for patients who do not receive surgery or for whom a surgical specimen 
is lacking. These patients will be included in the denominator.  
 
Patients who undergo surgical resection (R0/R1) will be included in analyses of patterns 
of recurrence and DFS. Both locoregional (in the pancreatic bed) and distant (liver, lungs, 
etc.) recurrence rates will be estimated in each arm. If we assume 85% of patients (n=43 
in each arm) will reach resection, recurrence rates can be estimated to within 15% (95% 
confidence interval). Distributions of DFS in each arm will be estimated using the method 
of Kaplan-Meier.  
 
Patients receiving at least one dose of drug will be included in the assessment of adverse 
events by treatment arm. Adverse event monitoring is conducted by the study 
coordinators, disease committee chair, Adverse Event Coordinator and study statistician 
on an ongoing basis, with notification to the DSMC and CTEP should any concerns 
arise. Any events reported through the CTEP-AERS system are reported immediately, 
and reports are sent to the above group for all other AEs on a monthly basis.  Fifty 
eligible patients in each arm are sufficient to estimate the probability of a particular 
toxicity to within 14% (95% confidence interval). Any toxicity occurring with at least a 6% 
probability is likely (95% chance) to be seen at least once. 
 
11.5 
Data and Safety Monitoring 
 
A Data and Safety Monitoring Committee will oversee the conduct of the study.  The 
Committee consists of four members from outside of the SWOG, 3 SWOG members, 3 
non-voting representatives from the National Cancer Institute (NCI), and the Group 
Statistician (non-voting).  The members of this Committee will receive confidential reports 
every 6 months from the SWOG Statistical Center, and will meet at the Group's bi-annual 
meetings as necessary.  The Committee will be responsible for decisions regarding 
possible termination and/or early reporting of the study. 
 
 
12.0 
DISCIPLINE REVIEW 
 
12.1 
Central Imaging Review 
 
Central imaging review will be performed by Dr. Namita Gandhi on baseline CT or MRI 
for all patients to confirm resectability for eligibility. See Section 15.1 for submission 
guidelines. 

 
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12.2  
Surgical Review and Quality Assurance 
 
All surgeries performed as part of this study will undergo a central review. The goal of this 
review is to verify that the resection was done according to the criteria specified in the 
protocol (Section 7.4). The surgical quality monitoring will be completed by the Surgical 
Study Chair (Dr. Syed Ahmad) within 30 days after surgery. Surgical data including 
operative notes and pathology reports will be reviewed. Any deviations in surgical quality 
that are identified will be addressed by the study chairs, Drs. Sohal and Ahmad. 
 
 
13.0 
REGISTRATION GUIDELINES 
 
13.1 
Registration Timing 
 
Patients must be registered prior to initiation of treatment (no more than three working 
days prior to planned start of treatment).  
 
13.2 
OPEN Registration Requirements 
 
The individual registering the patient must have completed the appropriate SWOG 
Registration Worksheet.  The completed form must be referred to during the registration 
but should not be submitted as part of the patient data. 
 
OPEN will also ask additional questions that are not present on the SWOG Registration 
Worksheet.  The individual registering the patient must be prepared to provide answers to 
the following questions: 
 
• 
Institution CTEP ID 
 
• 
Protocol Number 
 
• 
Registration Step 
 
• 
Treating Investigator 
 
• 
Credit Investigator 
 
• 
Patient Initials 
 
• 
Patient’s Date of Birth 
 
• 
Patient SSN (SSN is desired, but optional.  Do not enter invalid 
numbers.) 
 
• 
Country of Residence 
 
• 
ZIP Code 
 
• 
Gender (select one): 
o 
Female Gender 
o 
Male Gender 
 
• 
Ethnicity (select one): 
o 
Hispanic or Latino 
o 
Not Hispanic or Latino 
• 
Unknown 

 
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a. 
Method of Payment (select one): 
• 
Private Insurance 
• 
Medicare 
• 
Medicare and Private Insurance 
• 
Medicaid 
• 
Medicaid and Medicare 
• 
Military or Veterans Sponsored NOS 
• 
Military Sponsored (Including Champus & Tricare) 
• 
Veterans Sponsored 
• 
Self Pay (No Insurance) 
• 
No Means of Payment (No Insurance) 
• 
Other 
• 
Unknown 
 
b. 
Race (select all that apply): 
• 
American Indian or Alaska Native 
• 
Asian 
• 
Black or African American 
• 
Native Hawaiian or other Pacific Islander 
• 
White 
• 
Unknown 
 
13.3 
Registration Procedures 
 
a. 
All site staff will use OPEN to enroll patients to this study.  OPEN is a web-based 
application and 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, or from the 
OPEN Patient Registration link on the SWOG CRA Workbench. 
 
b. 
Prior to accessing OPEN site staff should verify the following: 
• 
All eligibility criteria have been met within the protocol stated timeframes and 
the affirmation of eligibility on the Registration Worksheet has been signed by 
the registering investigator or another investigator designate. Site staff 
should refer to Section 5.0 to verify eligibility. 
 
• 
All patients have signed an appropriate consent form and HIPAA 
authorization form (if applicable). 
 
c. 
Access requirements for OPEN: 
• 
Site staff will need to be registered with CTEP and have a valid and active 
CTEP-IAM account. This is the same account (user ID and password) used 
for the CTSU members' web site. 
 
• 
To perform registrations on SWOG protocols you must have an equivalent 
'Registrar' role on the SWOG roster.  Role assignments are handled through 
SWOG. 
 
Note:  The OPEN system will provide the site with a printable confirmation of 
registration and treatment information.  Please print this confirmation for your 
records. 
 
d. 
Further instructional information is provided on the OPEN tab on the CTSU 
members’ side of the website at https://www.ctsu.org or at https://open.ctsu.org.   
 For any additional questions contact the CTSU Help Desk at 1-888-823-5923 or 
ctsucontact@westat.com.   
 

 
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13.4 
Exceptions to SWOG registration policies will not be permitted. 
 
a. 
Patients must meet all eligibility requirements. 
 
b. 
Institutions must be identified as approved for registration. 
 
c. 
Registrations may not be cancelled. 
 
d. 
Late registrations (after initiation of treatment) will not be accepted. 
 
 
14.0 
DATA SUBMISSION SCHEDULE 
 
14.1 
Data Submission Requirement 
 
Data must be submitted according to the protocol requirements for ALL patients 
registered, whether or not assigned treatment is administered, including patients deemed 
to be ineligible.  Patients for whom documentation is inadequate to determine eligibility 
will generally be deemed ineligible 
 
14.2 
Master Forms 
 
Master forms can be found on the protocol abstract page on the SWOG website 
(www.swog.org) and (with the exception of the sample consent form and the Registration 
Worksheet) must be submitted on-line via the Web; see Section 14.3a for details. 
 
14.3 
Data Submission Procedures 
 
a. 
SWOG institutions must submit data electronically via the Web using Medidata 
Rave® at the following url: 
 
https://login.imedidata.com/selectlogin  
 
1. 
If prompted, select the ‘CTEP-IAM IdP’ link. 
 
2. 
Enter your valid and active CTEP-IAM userid and password.  This is the 
same account used for the CTSU members’ web site and OPEN. 
 
b. 
You may also access Rave® via the SWOG CRA Workbench.  Go to the SWOG 
web site (http://swog.org) and logon to the Members Area using your SWOG 
Roster ID Number and password. After you have logged on, click on 
Workbenches, then CRA Workbench to access the home page for the CRA 
Workbench and follow the link to Rave® provided in the left-hand navigation 
panel. 
 
To access the CRA Workbench the following must be done (in order): 
 
1. 
You are entered into the SWOG Roster and issued a SWOG Roster ID 
Number, 
 
2. 
You are associated as an investigator or CRA/RN at the institution where 
the patient is being treated or followed, 
 
3. 
Your Web User Administrator has added you as a web user and has 
given you the appropriate system permissions to view data for that 
institution. 
 

 
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For assistance with points 1 and 2 call the Operations Office at 210/614-8808.  
For point 3, contact your local Web User Administrator (refer to the "Who is my 
Web User Administrator?" function on the swog.org Members logon page). 
 
For difficulties with the CRA Workbench, please email  
technicalquestion@crab.org.  
 
14.4 
Data Submission Overview and Timepoints  
 
a. 
WITHIN 7 DAYS OF REGISTRATION: 
 
Submit the following: 
 
S1505 Onstudy Form 
 
Baseline Tumor Assessment Form (RECIST 1.1) 
 
Pathology Report * 
 
S1505 Local Radiology Review Checklist 
 
Radiology reports from all scans performed to assess disease at baseline. * 
 
Images from scans performed to assess disease at baseline as specified in 
Section 15.1. Submit via TRIAD for Central Imaging Review.  
 
*(NOTE: Upload reports via the Source Documentation: Baseline form in Rave®.) 
 
b. 
WITHIN 14 DAYS AFTER EACH CYCLE OF TREATMENT 
 
Submit the following: 
 
S1505 Treatment Summary Form 
 
S1505 Adverse Event Summary Form 
 
c. 
WITHIN 14 DAYS AFTER EACH DISEASE ASSESSMENT (both pre-operative 
re-staging and post-operative surveillance scans): 
 
Submit the following:  
 
Follow Up Tumor Assessment Form (RECIST 1.1)  
 
Radiology reports from all scans performed to assess disease. (NOTE: Upload 
reports via the Source Documentation: Follow-up form in Rave®.) 
 
d. 
WITHIN 14 DAYS AFTER PROTOCOL SURGERY:  
 
Submit the following:  
 
S1505 Surgical Summary Form 
 
Operative report (NOTE: Upload reports via the Source Documentation: Surgery 
form in Rave®.)  
 
Pathology report corresponding to the surgical specimen (NOTE: Upload reports 
via the Source Documentation: Surgery form in Rave®.)  

 
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Tissue from protocol surgery as specified in Section 15.2 
 
e. 
AFTER 
PROTOCOL 
SURGERY 
AND 
PRIOR 
TO 
POST-OPERATIVE 
TREATMENT:  
 
Submit the S1505 Surgical Adverse Event Summary Form 
 
f. 
WITHIN 14 DAYS OF DISCONTINUATION OF TREATMENT:  
 
Submit the following:  
 
Off Treatment Notice  
 
S1505 Treatment Form  
 
S1505 Adverse Event Form  
 
If patient went off protocol treatment prior to surgery, also submit the S1505 
Surgical Summary Form 
 
g. 
WITHIN 14 DAYS OF PROGRESSION/RECURRENCE:  
 
Follow Up Tumor Assessment Form (RECIST 1.1) documenting date, site and 
method for determining progression/recurrence.  
 
Radiology reports from all scans performed to assess disease. (NOTE: Upload 
reports via the Source Documentation: Follow-up form in Rave®.)  
 
h. 
AFTER OFF TREATMENT, EVERY 3 MONTHS FOR THE FIRST YEAR, 
EVERY 6 MONTHS FOR THE SECOND AND THIRD YEARS, THEN 
ANNUALLY UNTIL 4 YEARS FROM REGISTRATION  
Submit the following: 
 
S1505 Follow Up Form 
 
Late Effects Form (if prior to treatment for progression or relapse or a second 
primary, and prior to non-protocol treatment, the patient experiences any severe 
[Grade ≥ 3] long term toxicity that has not been previously reported) 
 
i. 
WITHIN 4 WEEKS OF KNOWLEDGE OF DEATH: 
 
Submit the Notice of Death documenting death information. In addition, if the 
patient was still on protocol treatment, submit materials specified in Section 
14.4b, or if the patient was no longer on treatment, submit a final Follow-Up 
Form. 
 

 
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15.0 
SPECIAL INSTRUCTIONS 
 
15.1 
Imaging Submission for Central Review (required for patient) 
 
CT or MRI images must be locally read and interpreted by the local site radiology 
service.  Imaging exams must then be submitted to the Imaging and Radiation Oncology 
Core (IROC) at Ohio via TRIAD Imaging Submission procedures for central data 
collection and quality control (QC) check as well as central review. 
 
CT or MRI images must be submitted to IROC Ohio for central review at Baseline. 
 
a. 
The following are recommended guidelines for CT scan quality: 
 
1. 
Neutral contrast 
 
a. 
Water or Volumen 
 
b. 
NO POSITIVE ORAL CONTRAST 
 
2. 
16- 64-detector MDCT 
 
3. 
INTRAVENOUS CONTRAST:  
 
a. 
150 ml (or weight based), 60ml saline  
 
b. 
Bolus Tracking technique 
 
c. 
Rate of contrast: at least 3-4 ml/sec 
 
4. 
4. 
Minimum two post-contrast phases (non-contrast is optional): 
 
a.  
Arterial phase – ideally bolus track (delayed arterial phase) 
 
b. 
Portal venous phase – 70-80 seconds 
 
5. 
0.6 mm collimation (thinnest collimation)  
 
6. 
Diagnostic Images:  
 
a. 
3 mm slice thickness, 3 mm recon interval  
 
b. 
2 recon: 1 mm x 0.8 mm recon (smallest slice with overlap)  
 
c. 
Reconstructions: 3 mm x 3 mm coronal MPRs for all phases. 
 
b. 
The following are recommended guidelines for MRI scan quality: 
 
1. 
MAGNET: 1.5 OR 3 T Magnet 
 
2. 
SURFACE COIL: Phased array torso coil 
 
3. 
SEQUENCES 
 
a. 
Breath-hold T2-weighted imaging with a single/multishot fast 
spin-echo sequence or a half-Fourier acquisition single-shot 
turbo spin-echo sequence with or without fat saturation 

 
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b. 
MRCP sequence: 2 D and/ or 3D. Breath-hold two-dimensional 
single-projection turbo spin-echo MR cholangiopancreatography 
performed at various angles to the coronal plane OR navigator-
triggered three-dimensional turbo spin-echo MR 
 
c. 
DW imaging performed by using respiratory-triggered single-shot 
echo-planar imaging with b values of 0, 100, and 800 sec/mm2 
 
d. 
Axial T1-weighted imaging with in-phase and opposed phase 
spoiled 3D gradient-echo sequences 
 
e. 
T1 W 3D GRE sequences (: Effective slice thickness 2 mm): 
unenhanced, arterial phase (AP), portal venous phase (PVP), 3-
minute late-phase.  
 
f. 
Subtraction images 
 
 
c. 
TRIAD Digital Image Submission  
 
TRIAD is the secure electronic image upload application utilized for IROC 
Services of this trial. TRIAD de-identifies and validates the images as they are 
transferred. 
 
1. 
TRIAD Access Requirements: 
 
TRIAD will be the sole means of image transfer to the IROC Ohio. 
TRIAD should be installed prior to study participant enrollment to ensure 
prompt secure, electronic submission of imaging. 
 
• 
Site staff who submit images through TRIAD will need to be 
registered with the Cancer Therapy Evaluation Program (CTEP) and 
have a valid and active CTEP-IAM account (see Section 13.2). 
• 
To submit images, the site user must be on the site’s affiliate 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.   
 
2. 
TRIAD Installations: 
 
After a user receives a CTEP-IAM account with the 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 
by 
following 
this 
link 
https://triadinstall.acr.org/triadclient/   
 
Questions regarding image submissions, including TRIAD, should be directed to 
SWOG1505@irocohio.org or call IROC Ohio at 614-293-2929. 
 
15.2 
Translational Medicine and Banking  
 
Specimens for translational medicine and banking (submitted to the SWOG Biospecimen 
Bank – Solid Tissue, Myeloma and Lymphoma Division, Lab #201 (optional for patient): 

 
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a. 
With patient’s consent, specimen must be submitted (see Sections 9.1 and 9.2): 
 
1. 
Formalin-fixed, paraffin-embedded (FFPE) tissue from surgical resection 
(1 block OR tissue section equivalent of at least 10 unstained slides OR 
10 unstained slides). 
 
b. 
Specimen collection and submission instructions can be accessed on the SWOG 
Specimen Submission webpage  
(https://www.swog.org/clinical-trials/biospecimen-resources/biospecimen-
processing-and-submission-procedures). 
 
c. 
Specimen collection kits are not being provided for this submission; sites will use 
institutional supplies. 
 
d. 
Specimen Labeling  
 
1. 
Solid tissue specimens must be labeled with the following: 
• 
SWOG patient number 
• 
Patient initials 
• 
Collection date, or procedure date 
• 
Site of collection (e.g., Lymph node, left breast, liver, etc.) 
• 
Specify whether tissue is from primary (P) or metastatic (M) 
• 
Surgical Pathology ID # (Accession#) and block number (e.g., 
A2, 3E, 2-1, B, etc.) must be on both the specimen label and the 
pathology report in order for the Bank to adequately match the 
specimen with any findings in the pathology report. 
 
 
16.0 
ETHICAL AND REGULATORY CONSIDERATIONS 
 
The following must be observed to comply with Food and Drug Administration regulations for the 
conduct and monitoring of clinical investigations; they also represent sound research practice: 
 
Informed Consent 
 
The principles of informed consent are described by Federal Regulatory Guidelines (Federal 
Register Vol. 46, No. 17, January 27, 1981, part 50) and the Office for Protection from Research 
Risks Reports:  Protection of Human Subjects (Code of Federal Regulations 45 CFR 46).  They 
must be followed to comply with FDA regulations for the conduct and monitoring of clinical 
investigations. 
 
Institutional Review 
 
This study must be approved by an appropriate institutional review committee as defined by 
Federal Regulatory Guidelines (Ref. Federal Register Vol. 46, No. 17, January 27, 1981, part 56) 
and the Office for Protection from Research Risks Reports:  Protection of Human Subjects (Code 
of Federal Regulations 45 CFR 46). 
 
Monitoring 
 
This study will be monitored by the Clinical Data Update System (CDUS) Version 3.0.  
Cumulative CDUS data will be submitted quarterly to CTEP by electronic means.  Reports are 
due January 31, April 30, July 31 and October 31. 

 
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Confidentiality 
 
Please note that the information contained in this protocol is considered confidential and should 
not be used or shared beyond the purposes of completing protocol requirements until or unless 
additional permission is obtained. 
 
16.1 
Adverse Event Reporting Requirements 
 
a. 
Purpose 
 
Adverse event data collection and reporting, which are required as part of every 
clinical trial, are done to ensure the safety of patients enrolled in the studies as 
well as those who will enroll in future studies using similar agents. Adverse 
events are reported in a routine manner at scheduled times during a trial. 
(Directions for routine reporting are provided in Section 14.0.) Additionally, 
certain adverse events must be reported in an expedited manner to allow for 
more timely monitoring of patient safety and care. The following guidelines 
prescribe expedited adverse event reporting for this protocol.  
 
b. 
Reporting method 
 
This study requires that expedited adverse events be reported using the Cancer 
Therapy Evaluation Program Adverse Event Reporting System (CTEP-AERS).   
 
CTEP's guidelines for CTEP-AERS can be found at http://ctep.cancer.gov. A 
CTEP-AERS report must be submitted to the SWOG Operations Office 
electronically via the CTEP-AERS Web-based application located at 
https://eapps-ctep.nci.nih.gov/ctepaers.  
 
In the rare event when internet connectivity is disrupted an electronic report 
MUST be submitted immediately upon re-establishment of internet connection.   
 
c. 
When to report an event in an expedited manner 
 
When the adverse event requires expedited reporting, submit the report within 10 
calendar days of learning of the event. 
 
d. 
Other recipients of adverse event reports 
 
The SWOG Operations Office will forward reports and documentation to the 
appropriate regulatory agencies and drug companies as required.  
 
Adverse events determined to be reportable to the Institutional Review Board 
responsible for oversight of the patient must be reported according to local policy 
and procedures.  
 
e. 
Expedited reporting for commercial agents 
 
Commercial reporting requirements are provided in Table 16.1. The commercial 
agents used in both arms of this study are fluorouracil, gemcitabine, nab-
paclitaxel, oxaliplatin, and pegfilgrastim. If there is any question about the 
reportability of an adverse event or if on-line CTEP-AERS cannot be used, 
please telephone or email the SAE Program at the Operations Office, 210/614-
8808 or adr@swog.org, before preparing the report. 

 
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Table 16.1. Expedited reporting requirements for adverse events experienced by 
patients Arm 1 or Arm 2 within 30 days of the last administration of the commercial 
agent(s).  All of the agents used in the study are commercial agents. 
 
ATTRIBUTION 
 
Grade 4 
 
Grade 5a 
Unexpected 
Expected 
Unexpected 
Expected 
Unrelated or 
Unlikely 
 
 
CTEP-
AERS 
CTEP-
AERS 
Possible, Probable, 
Definite 
CTEP-
AERS 
 
CTEP-
AERS 
CTEP-
AERS 
CTEP-AERS:  Indicates an expedited report is to be submitted via CTEP-AERS 
within 10 calendar days of learning of the eventb. 
 
a This includes all deaths within 30 days of the last dose of treatment with a 
commercial agent(s), regardless of attribution. Any death that occurs more than 
30 days after the last dose of treatment with a commercial agent(s) and is 
attributed (possibly, probably, or definitely) to the agent(s) and is not due to 
cancer recurrence must be reported according to the instructions above. 
 
b Submission of the on-line CTEP-AERS report plus any necessary amendments 
generally completes the reporting requirements. You may, however, be asked to 
submit supporting clinical data to the Operations Office in order to complete the 
evaluation of the event. If requested, the specified data should be sent within 5 
calendar days by fax to 210-614-0006. 
 
 
f. 
Reporting Pregnancy, Fetal Death, and Death Neonatal 
 
1. 
Pregnancy Study participants who become pregnant while on study; that 
pregnancy should be reported in an expedited manner via CTEP-AERS 
as Grade 3 “Pregnancy, puerperium and perinatal conditions – 
Other (pregnancy)” under the Pregnancy, puerperium and perinatal 
conditions SOC. 
 
Additionally, the pregnancy outcome for patients on study should be 
reported via CTEP-AERS at the time the outcome becomes known, 
accompanied by the same Pregnancy Report Form used for the initial 
report. 
 
2. 
Pregnancy Loss  Pregnancy loss is defined in CTCAE as “Death in 
utero.” Pregnancy loss should be reported expeditiously as Grade 4 
“Pregnancy loss” under the Pregnancy, puerperium and perinatal 
conditions SOC.   
 
A Pregnancy loss should NOT be reported as a Grade 5 event under the 
Pregnancy, puerperium and perinatal conditions SOC, as currently 
CTEP-AERS recognizes this event as a patient death. 
 
3. 
Death Neonatal  Death neonatal is defined in CTCAE as “Newborn 
death occurring during the first 28 days after birth  A neonatal death 
should be reported expeditiously as Grade 4 “Death neonatal” under 
the General disorders and administration SOC. 

 
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Neonatal death should NOT be reported as a Grade 5 event under the 
General disorders and administration SOC as currently CTEP-AERS 
recognizes this event as a patient death. 
 
NOTE:  When submitting CTEP-AERS reports for “Pregnancy, “Pregnancy loss”, 
or “Neonatal loss”, the Pregnancy Information Form should also be completed 
and faxed with any additional medical information to 301-230-0159.  The 
potential risk of exposure of the fetus to the investigational agent(s) or 
chemotherapy agent(s) should be documented in the “Description of Event” 
section of the CTEP-AERS report. 
 
The Pregnancy Information Form is available at:   
http://ctep.cancer.gov/protocolDevelopment/adverse_effects.htm. 
 
 

 
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17.0 
BIBLIOGRAPHY 
 
1  
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. 
CA: a cancer journal for clinicians. Mar 2015;65(2):87-108. 
Torre LA, Bray F, Siegel RL, 
Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA: a cancer journal for 
clinicians. Mar 2015;65(2):87-108. 
 
2  
AJCC. AJCC Cancer Staging Manual. Seventh ed: Springer, New York; 2010. 
 
3  
Winter JM, Brennan MF, Tang LH, et al. Survival after resection of pancreatic adenocarcinoma: 
results from a single institution over three decades. Annals of surgical oncology. Jan 
2012;19(1):169-175. 
 
4  
Boeck S, Ankerst DP, Heinemann V. The role of adjuvant chemotherapy for patients with 
resected pancreatic cancer: systematic review of randomized controlled trials and meta-analysis. 
Oncology. 2007;72(5-6):314-321. 
 
5  
Oettle H, Neuhaus P, Hochhaus A, et al. Adjuvant chemotherapy with gemcitabine and long-term 
outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. 
JAMA : the journal of the American Medical Association. Oct 9 2013;310(14):1473-1481. 
 
6  
Regine WF, Winter KA, Abrams RA, et al. Fluorouracil vs gemcitabine chemotherapy before and 
after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a 
randomized controlled trial. JAMA : the journal of the American Medical Association. Mar 5 
2008;299(9):1019-1026. 
7  
Liao WC, Chien KL, Lin YL, et al. Adjuvant treatments for resected pancreatic adenocarcinoma: a 
systematic review and network meta-analysis. The Lancet. Oncology. Oct 2013;14(11):1095-
1103. 
 
8  
Liao WC, Chien KL, Lin YL, et al. Adjuvant treatments for resected pancreatic adenocarcinoma: a 
systematic review and network meta-analysis. The Lancet. Oncology. Oct 2013;14(11):1095-
1103. 
 
9  
Sohal DP, Walsh RM, Ramanathan RK, Khorana AA. Pancreatic adenocarcinoma: treating a 
systemic disease with systemic therapy. Journal of the National Cancer Institute. Mar 
2014;106(3):dju011. 
 
10  
Rhim AD, Mirek ET, Aiello NM, et al. EMT and dissemination precede pancreatic tumor formation. 
Cell. Jan 20 2012;148(1-2):349-361. 
 
11  
Gnerlich JL, Luka SR, Deshpande AD, et al. Microscopic margins and patterns of treatment 
failure in resected pancreatic adenocarcinoma. Archives of surgery. Aug 2012;147(8):753-760. 
 
12  
Iacobuzio-Donahue CA, Fu B, Yachida S, et al. DPC4 gene status of the primary carcinoma 
correlates with patterns of failure in patients with pancreatic cancer. Journal of clinical oncology : 
official journal of the American Society of Clinical Oncology. Apr 10 2009;27(11):1806-1813. 
 
13  
Hishinuma S, Ogata Y, Tomikawa M, Ozawa I, Hirabayashi K, Igarashi S. Patterns of recurrence 
after curative resection of pancreatic cancer, based on autopsy findings. Journal of 
gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract. Apr 
2006;10(4):511-518. 
 
14  
Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic 
pancreatic cancer. The New England journal of medicine. May 12 2011;364(19):1817-1825. 
 

 
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15  
Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel 
plus gemcitabine. The New England journal of medicine. Oct 31 2013;369(18):1691-1703. 
 
16  
Blazer M, Wu C, Goldberg RM, et al. Neoadjuvant Modified (m) FOLFIRINOX for Locally 
Advanced Unresectable (LAPC) and Borderline Resectable (BRPC) Adenocarcinoma of the 
Pancreas. Annals of surgical oncology. Apr 2015;22(4):1153-1159. 
 
17  
Blazer M, Wu C, Goldberg RM, et al. Neoadjuvant Modified (m) FOLFIRINOX for Locally 
Advanced Unresectable (LAPC) and Borderline Resectable (BRPC) Adenocarcinoma of the 
Pancreas. Annals of surgical oncology. Apr 2015;22(4):1153-1159. 
 
18  
Chllamma M, Cook N, Giby K, et al. FOLFIRINOX for advanced pancreatic cancer: The Princess 
Margaret experience. Journal of Clinical Oncology. 2015;33(Suppl 3):Abstr 417. 
 
19  
James ES, Xiangyu Cong XY, Carol Hahn, Kristin Kaley, Jia Li, Jeremy S. Kortmansky, Neal A. 
Fischbach, Charles Cha, Ronald R Salem, Stacey Stein, Howard S. Hochster, Jill Lacy. Final 
analysis of a phase II study of Yale-modified FOLFIRINOX (mFOLFIRINOX) in metastatic 
pancreatic cancer (MPC). Journal of Clinical Oncology. 2015;33(Suppl 3):Abstr 395. 
 
20  
Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel 
plus gemcitabine. The New England journal of medicine. Oct 31 2013;369(18):1691-1703. 
 
21  
Goldstein D, El-Maraghi RH, Hammel P, et al. nab-Paclitaxel plus gemcitabine for metastatic 
pancreatic cancer: long-term survival from a phase III trial. Journal of the National Cancer 
Institute. Feb 2015;107(2). 
 
22  
Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic 
pancreatic cancer. The New England journal of medicine. May 12 2011;364(19):1817-1825. 
 
23  
Oettle H, Neuhaus P, Hochhaus A, et al. Adjuvant chemotherapy with gemcitabine and long-term 
outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. 
JAMA : the journal of the American Medical Association. Oct 9 2013;310(14):1473-1481. 
 
24  
Regine WF, Winter KA, Abrams RA, et al. Fluorouracil vs gemcitabine chemotherapy before and 
after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a 
randomized controlled trial. JAMA : the journal of the American Medical Association. Mar 5 
2008;299(9):1019-1026. 
 
25  
Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone 
for resectable gastroesophageal cancer. The New England journal of medicine. Jul 6 
2006;355(1):11-20. 
 
26  
Evans DB, Varadhachary GR, Crane CH, et al. Preoperative gemcitabine-based chemoradiation 
for patients with resectable adenocarcinoma of the pancreatic head. Journal of clinical oncology : 
official journal of the American Society of Clinical Oncology. Jul 20 2008;26(21):3496-3502. 
 
27  
Varadhachary GR, Wolff RA, Crane CH, et al. Preoperative gemcitabine and cisplatin followed by 
gemcitabine-based chemoradiation for resectable adenocarcinoma of the pancreatic head. 
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. Jul 20 
2008;26(21):3487-3495. 
 
28  
Gillen S, Schuster T, Meyer Zum Buschenfelde C, Friess H, Kleeff J. Preoperative/neoadjuvant 
therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection 
percentages. PLoS medicine. Apr 2010;7(4):e1000267. 
 

 
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29  
Andriulli A, Festa V, Botteri E, et al. Neoadjuvant/preoperative gemcitabine for patients with 
localized pancreatic cancer: a meta-analysis of prospective studies. Annals of surgical oncology. 
May 2012;19(5):1644-1662. 
 
30  
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: 
revised RECIST guideline (version 1.1). European journal of cancer. Jan 2009;45(2):228-247. 
 
31  
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. 
CA: a cancer journal for clinicians. Mar 2015;65(2):87-108. 
 
32  
AJCC. AJCC Cancer Staging Manual. Seventh ed: Springer, New York; 2010. 
 
33  
Winter JM, Brennan MF, Tang LH, et al. Survival after resection of pancreatic adenocarcinoma: 
results from a single institution over three decades. Annals of surgical oncology. Jan 
2012;19(1):169-175. 
 
34  
Boeck S, Ankerst DP, Heinemann V. The role of adjuvant chemotherapy for patients with 
resected pancreatic cancer: systematic review of randomized controlled trials and meta-analysis. 
Oncology. 2007;72(5-6):314-321. 
 
35  
Oettle H, Neuhaus P, Hochhaus A, et al. Adjuvant chemotherapy with gemcitabine and long-term 
outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. 
JAMA : the journal of the American Medical Association. Oct 9 2013;310(14):1473-1481. 
 
36  
Regine WF, Winter KA, Abrams RA, et al. Fluorouracil vs gemcitabine chemotherapy before and 
after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a 
randomized controlled trial. JAMA : the journal of the American Medical Association. Mar 5 
2008;299(9):1019-1026. 
 
37  
Liao WC, Chien KL, Lin YL, et al. Adjuvant treatments for resected pancreatic adenocarcinoma: a 
systematic review and network meta-analysis. The Lancet. Oncology. Oct 2013;14(11):1095-
1103. 
 
38  
Sohal DP, Walsh RM, Ramanathan RK, Khorana AA. Pancreatic adenocarcinoma: treating a 
systemic disease with systemic therapy. Journal of the National Cancer Institute. Mar 
2014;106(3):dju011. 
 
39  
Oettle H, Neuhaus P, Hochhaus A, et al. Adjuvant chemotherapy with gemcitabine and long-term 
outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. 
JAMA : the journal of the American Medical Association. Oct 9 2013;310(14):1473-1481. 
 
40  
Regine WF, Winter KA, Abrams RA, et al. Fluorouracil vs gemcitabine chemotherapy before and 
after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a 
randomized controlled trial. JAMA : the journal of the American Medical Association. Mar 5 
2008;299(9):1019-1026. 
 
 
 

 
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18.0 
APPENDIX 
 
18.1 
TISSUE-BASED 
TRANSLATIONAL 
MEDICINE 
DETAILS: 
IMMUNOLOGIC 
PREDICTORS OF THERAPEUTIC RESPONSE TO NEOADJUVANT THERAPY FOR 
PANCREATIC ADENOCARCINOMA OBJECTIVES:   
 
 
18.2 
Imaging Translational Medicine Details 
 
18.3 
Instructions for the SWOG Specimen Bank 
 
 
 

 
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18.1 
Tissue-based Translational Medicine Details: Immunologic Predictors of Therapeutic 
Response to Neoadjuvant Therapy for Pancreatic AdenocarcinomaObjectives:  
  
1. 
To assess the effect of mFOLFIRINOX and Gem/nab-P on the tumor 
immune infiltrate.  
 
2. 
To estimate the relationship between the tumor immune infiltrate and 
clinical outcomes:  
 
I. 
Pathologic response  
II. 
Disease-free survival  
III. 
Overall survival  
 
a. 
Background: 
 
The immune response to cancer is a critical determinant of long term outcomes 
to therapy for many cancers. In pancreatic ductal adenocarcinoma (PDAC), 
leukocytes are a common feature of the desmoplastic reaction that surrounds 
malignant cells. This infiltrate contains multiple immune cell subsets including 
myeloid cells (e.g. macrophages, neutrophils) as well as lymphocytes (e.g. T 
cells, B cells). Whereas myeloid cell infiltrates are a prognostic determinant of 
poor survival and portend an increased likelihood for metastasis (1,2,3), CD3+ T 
cells have been associated with improved survival in patients with surgically 
resected PDAC. (4,5) However, the impact of chemotherapy on the immune 
reaction to PDAC remains ill-defined. Understanding this biology has broad-
reaching implications, as chemotherapy is a common therapeutic backbone for 
testing novel immunotherapeutics (e.g. inhibitors of PD-1/PD-L1, CD40, IDO, 
CCR2, and JAK1/2 among others). Here, we will test the hypothesis that 
chemotherapy induces the infiltration of activated and functional T cells 
into PDAC tumors which correlates with improved clinical outcomes.  
 
The immune modulatory effects of chemotherapy on the tumor microenvironment 
are well-established in preclinical models. Both gemcitabine and nab-paclitaxel 
have been found to stimulate macrophages with antitumor properties. (6, 7) In 
addition, oxaliplatin has been shown to induce an immunogenic form of tumor 
cell death with implications for stimulating tumor-specific T cell immunity. (8) 
However, a detailed understanding of the impact of chemotherapy on the 
immune reaction in human PDAC is currently limited. This knowledge, though, 
of how chemotherapy alters the immune reaction to PDAC is fundamental 
to the design of effective treatment regimens that aim to combine 
chemotherapy with immunotherapy.  
 
In a study of patients with surgically resected PDAC who had received 
neoadjuvant 
treatment 
with 
gemcitabine/cisplatin/docetaxel 
followed 
by 
chemoradiotherapy (300cGy/10 fractions plus oxaliplatin/cisplatin), treatment 
altered the immune infiltrate by increasing the ratio of effector (CD8+) to 
regulatory (Foxp3+) T cells found in tumor tissue – a finding that correlated with 
improved overall survival. (9) A separate study evaluating gemcitabine/S-1 
followed by chemoradiotherapy (300cGy/10 fractions + S-1) also reported a 
correlation between overall survival and increased effector (CD8+) T cell 
infiltrates detected in resected tissue. (10) 
 

 
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However, the relationship between T cell density and overall survival seen 
in these studies is only predictive for a subset of patients indicating that 
the mere presence of T cells is not always prognostic. Moreover, these 
studies have not addressed the remarkable spatial heterogeneity of infiltrating 
immune cells that can be seen in PDAC. To this end, the findings reported are 
consistent with the notion that the type and location of T cells within tumors will 
be equally as important as their density. (11) CD3+ T cell infiltrates are more 
prominent in regions of chronic pancreatitis compared to the tumor bed. (12)  In 
addition, CD3+ T cells are commonly found trapped in tumor tissue where they 
may be functionally paralyzed due at least in part to a lack of key components of 
the T cell receptor (i.e. CD3zeta chain) that are necessary for effector activity. 
(13) In contrast, direct interaction between CD3+ T cells and malignant cells is 
infrequent. In the proposed study, we will conduct a comprehensive assessment 
of the impact of chemotherapy on the immune reaction to test the hypothesis 
that chemotherapy can induce the infiltration of activated and functional T 
cells in PDAC. This knowledge is expected to provide key insights into patient 
subsets that may respond to immunotherapy and mechanisms that will need to 
be targeted to improve the likelihood of productive outcomes with 
immunotherapy.  
 
b. 
Eligibility 
 
All 
patients 
enrolled 
in 
S1505 
with 
surgically 
resected 
pancreatic 
adenocarcinoma specimens banked per protocol.  
 
c. 
Experimental Approach and Analysis 
 
To study the immune microenvironment in PDAC, the co-PI of this study, Dr. 
Gregory Beatty, has developed multiplex immunohistochemistry panels to detect 
multiple immune cell subsets in tissues and to determine their spatial relationship 
with malignant cells (Fig. 1). Dr. Beatty has strong expertise in the analysis of the 
immune 
microenvironment 
of 
cancer 
and 
the 
application 
of 
novel 
immunotherapies for the treatment of PDAC. In this proposal, Dr. Beatty’s 
research group will apply multiplex immunohistochemistry to the analysis of 
samples being collected from patients enrolled in SWOG S1505 (PI, Dr. 
Davendra Sohal). This randomized Phase II study investigates the therapeutic 
impact of perioperative treatment with mFOLFIRINOX versus gemcitabine/nab-
paclitaxel (Gem/nab-P) in patients with surgically resectable PDAC. These two 
chemotherapeutic regimens are actively being studied in combination with 
immunotherapy. Thus, this proposal brings together the clinical expertise of Dr. 
Sohal and the translational expertise of Dr. Beatty to understand the impact of 
neoadjuvant chemotherapy on T cell immune infiltrates in PDAC. 
 
 
 

 
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For controls, we will use resected pancreatic cancer specimens from PDAC 
patients who underwent surgery for resectable disease, without prior neoadjuvant 
therapy. These specimens will be obtained from a biorepository maintained at the 
Huntsman Cancer Institute (HCI) by our co-investigator, Dr. Ignacio Garrido-
Laguna. This biorepository captures tumor specimens from patients enrolled in a 
longitudinal study since 2001. As of July 2017, the database has information on 
1130 patients with pancreatic adenocarcinoma. Of these, 286 have had 
resection, of which 242 had resections without any neoadjuvant treatment. These 
will be used as controls for this study. Information captured includes the following 
variables: sex, date of diagnosis, date of surgery, date of death/last follow-up, 
ECOG PS, location of tumor (head, body, tail), tumor size, grade, resection 
margin (R0 vs R1), pathologic stage, adjuvant therapy (yes/no). All the controls 
will be from the HCI, and we will limit controls to match the S1505 population, by 
including patients of ages 18-75 and ECOG PS 0-1.  
 
d. 
Statistical Considerations 
 
Tissues will be stained using the automated Ventana Discovery Ultra staining 
platform available in the Beatty Laboratory. Whole slide imaging of stained 
tissues will be captured using the Aperio ScanScope image scanner. Images will 
be deconvoluted and reconstructed to identify individual cell populations (Fig. 2) 
for cellular quantification and determination of x,y coordinates to allow 
exploratory spatial analyses to detect interactions between (i) T cell populations 
(e.g. CD8 and Foxp3), (ii) T cells and tumor cells (e.g. CD8 and CK19 cell 
populations), and (iii) T cells and CD68+ myeloid cells (Fig. 3). In addition, we will 
assess PDL1 staining and its relationship to T cell infiltration. This analysis will be 
performed in the Beatty Laboratory. Findings will be presented using box and 
whisker plots to show cell frequencies and ratios. 
 

 
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Planned study accrual is 100 eligible patients. Assuming that at least 75% of 
patients reach surgical resection, and 90% compliance with specimen 
submission, we expect to have approximately 68 samples for evaluation of tumor 
immune infiltrate. Although we treat the cell frequencies as approximately 
normally distributed for power calculations, the analysis methods will be adapted 
as appropriate to their observed distributions. 
 
Aim 1:  
With 68 treated samples and 68 untreated control samples, we will have 84% 
power to detect a 0.45 SD effect size (difference between group means, divided 
by common standard deviation) assuming a 2-sided 10% type I error. A 
comparison of the study samples according to treatment arm will have 80% 
power to detect a 0.6 SD effect size, assuming a 2-sided 10% type I error.  
 
Aim 2:  
The immunohistochemistry findings will be correlated with pathological response 
via logistic regression, with binary outcome defined as complete or moderate 
response vs. minimal, poor or no response. Assuming 40% of resected patients 
have complete or moderate response, treating the tumor infiltrate measures as 
dichotomous (split at median value), and combining treatment arms, 68 samples 
will provide 79% power to detect an odds ratio of 4.1 for the association between 
high vs. low cell frequency levels and response, assuming a 2-sided 10% type I 
error.  
 
Immunohistochemistry findings will also be correlated with DFS and OS in the 
combined treatment arms via Cox regression models. With 68 study samples, we 
will have at least 80% power to detect a hazard ratio of 2.2 in DFS or OS 
according to high vs. low cell frequency, assuming a 2-sided 10% type I error.  
We will also estimate the associations of immunohistochemistry findings with 
clinical outcomes within each treatment arm, but statistical power to test for 
interactive effects is limited by the small sample sizes. 
 
e. 
Procedures 
 
Please review Section 15.2 for specimen submission procedures. 
 
The SWOG Biospecimen Bank will ship tissue specimens for analysis of surgical 
tissue specimens to be performed by the Beatty Laboratory:  
 
Gregory Beatty, MD, PhD  
University of Pennsylvania Perelman School of Medicine  
Center for Cellular Immunotherapies  
PCAM South Pavilion, Rm 8-107  
3400 Civic Center Blvd. Bldg 421  
Philadelphia, PA 19104-5156  
Office: 
215-746-7764; 
Fax: 
215-573-8590; 
Email: 
gregory.beatty@uphs.upenn.edu    

 
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f. 
References 
 
1  
Ino Y, Yamazaki-Itoh R, Shimada K, et al. Immune cell infiltration as an indicator of the immune 
microenvironment of pancreatic cancer. Br J Cancer 2013;108: 914-23. 
 
2  
Wang WQ, Liu L, Xu HX, et al. Infiltrating immune cells and gene mutations in pancreatic ductal 
adenocarcinoma. Br J Surg 2016;103: 1189-99. 
 
3  
Di Caro G, Cortese N, Castino GF, et al. Dual prognostic significance of tumour-associated 
macrophages in human pancreatic adenocarcinoma treated or untreated with chemotherapy. Gut 
2016;65: 1710-20. 
 
4  
Ino Y, Yamazaki-Itoh R, Shimada K, et al. Immune cell infiltration as an indicator of the immune 
microenvironment of pancreatic cancer. Br J Cancer 2013;108: 914-23. 
 
5  
Tewari N, Zaitoun AM, Arora A, Madhusudan S, Ilyas M, Lobo DN. The presence of tumour-
associated lymphocytes confers a good prognosis in pancreatic ductal adenocarcinoma: an 
immunohistochemical study of tissue microarrays. BMC Cancer 2013;13: 436. 
 
6  
Di Caro G, Cortese N, Castino GF, et al. Dual prognostic significance of tumour-associated 
macrophages in human pancreatic adenocarcinoma treated or untreated with chemotherapy. Gut 
2016;65: 1710-20. 
 
7  
Cullis J, Siolas D, Avanzi A, Barui S, Maitra A, Bar-Sagi D. Macropinocytosis of Nab-paclitaxel 
Drives Macrophage Activation in Pancreatic Cancer. Cancer immunology research 2017. 
 
8  
Pfirschke C, Engblom C, Rickelt S, et al. Immunogenic Chemotherapy Sensitizes Tumors to 
Checkpoint Blockade Therapy. Immunity 2016;44: 343-54.  
 
9  
Shibuya KC, Goel VK, Xiong W, et al. Pancreatic ductal adenocarcinoma contains an effector and 
regulatory immune cell infiltrate that is altered by multimodal neoadjuvant treatment. PLoS One 
2014;9: e96565.  
 
10  
Homma Y, Taniguchi K, Murakami T, et al. Immunological impact of neoadjuvant 
chemoradiotherapy in patients with borderline resectable pancreatic ductal adenocarcinoma. Ann 
Surg Oncol 2014;21: 670-6. 
 
11  
Galon J, Pages F, Marincola FM, et al. Cancer classification using the Immunoscore: a worldwide 
task force. J Transl Med 2012;10: 205. 
 
12  
Helm O, Mennrich R, Petrick D, et al. Comparative characterization of stroma cells and ductal 
epithelium in chronic pancreatitis and pancreatic ductal adenocarcinoma. PLoS One 2014;9: 
e94357. 
 
13  
von Bernstorff W, Voss M, Freichel S, et al. Systemic and local immunosuppression in pancreatic 
cancer patients. Clin Cancer Res 2001;7: 925s-32s. 
 
 
 

 
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18.2 
Imaging Translational Medicine Details: S1505 Radiology Correlative (Retrospective): 
Quantitative CT Measurement of Muscle and Adipose Tissue and Prognosis in Patients 
with Resectable Pancreatic Adenocarcinoma” 
 
a. 
Objectives 
 
1. 
Primary: To estimate the associations of baseline CT measurements of 
muscle and adipose tissue with overall survival (OS). 
 
2. 
Secondary: To estimate the associations of baseline CT measurements 
of muscle and adipose tissue with baseline clinical and laboratory 
variables, and with weight loss during treatment 
 
3. 
Secondary: To estimate the associations of baseline CT measurements 
of muscle mass (skeletal muscle index and skeletal muscle density, 
summarized below) with chemotherapy toxicity.  
 
4. 
Secondary: To estimate the associations of baseline CT measurements 
of adipose tissue (VAT, SAT, IMAT) with chemotherapy toxicity. 
 
b. 
Background 
 
Weight loss is present in 40% of patients with resectable pancreatic cancer and 
worsens prognosis. (1)  
 
Advances in imaging have enabled quantitative measurement of muscle mass, 
muscle quality, and adipose tissue. CT measurements of skeletal muscle mass 
include skeletal muscle index and skeletal muscle density; measurements of 
adipose tissue include visceral adipose tissue (VAT), subcutaneous adipose 
tissue (SAT), and intermuscular adipose tissue (IMAT). These measurements 
can easily be obtained from analysis of CT scans obtained during routine patient 
care. (2, 3)    
 
These CT measurements have the potential to help determine prognostic 
categories in cancer patients. For example, measurements of muscle attenuation 
(skeletal muscle density) were prognostic in heavy smokers at risk for lung 
cancer. (4)  In a retrospective cohort of 199 patients with head of pancreas 
cancer from a single European institution, preoperative CT scans were analyzed 
at L3 level using predefined Hounsfield unit (HU) ranges, the total cross‐sectional 
area and mean attenuation of skeletal muscle tissue (−29 to 150 HU), VAT (−150 
to −50 HU), SAT (−190 to −30 HU), and IMAT (−190 to −30 HU) were evaluated. 
They reported significant differences in survival by tertiles of muscle attenuation: 
The median survival for low attenuation was 10.8 months, middle 17.4 months, 
and high was 18.5 months. Survival comparisons showed a significant difference 
between the low attenuation and the other 2 groups; median survival of 10.8 
(95% CI: 8.8–12.8) vs. 17.4 (95% CI: 14.7–20.1), and 18.5 months (95% CI: 9.2–
27.8), respectively (P = 0.008). (5)  
 
The relation of muscle mass and adipose tissue to treatment toxicity is an area of 
active investigation. Adipose tissue measurements were related to surgical 
toxicity and total psoas area was significantly associated with stereotactic 
radiation toxicity in another group of pancreatic cancer patients. (6, 7) The 
association of muscle mass and adipose tissue measurements in pancreatic 
cancer patients with chemotherapy response and toxicity is unknown.  

 
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It is expected that in the near future, quantitative CT measurements of muscle 
and adipose tissue phenotypes will be made routinely on clinical CT scans in 
order to improve risk stratification and help guide appropriate management. 
Current barriers to clinical application of this knowledge include the ability to 
automate analyses of CT images, standardization of CT measurements and 
definitions of sarcopenia, and translation of research findings to clinical 
situations. 
 
SWOG 1505 is a randomized prospective comparison in operable pancreatic 
cancer of preoperative FOLFIRINOX to gemcitabine + nab paclitaxel, followed by 
resection, and adjuvant chemotherapy. The primary outcome measure is overall 
survival. 
 
c. 
Experimental Research Technique 
 
Archived CT scans will be analyzed. Total abdominal muscles will be segmented 
using commercially available, externally validated software (Osirix Pixmeo SARL, 
Berne Switzerland). We selected this software for two reasons: (1) in our 
systematic review of nearly 600 CT peer-reviewed research studies of 
sarcopenia, this was the most frequently used software [Amini, 2018] and (2) we 
have validated the semi-automated version of this software with a reference 
standard of manual segmentation in 500 of our own subjects. We will estimate 
the following baseline CT measurements of muscle and adipose tissue: 
 
Definitions 
• 
Muscle groups: all skeletal muscle (i.e., psoas, posterior paravertebral, 
and abdominal muscles) will be measured on a single CT image at the 
level of L3 pedicle. 
• 
Muscle indices (using -29 to 150 HU thresholding):  
 
• 
Skeletal muscle cross sectional area (CSA) – Total CSA of 
muscles  
• 
Skeletal muscle index (SMI) - CSA in cm2/ patient height in m2 
• 
Skeletal muscle density (SMD) - Average muscle attenuation  
• 
Fat indices (using -195 to -30 HU thresholding): 
• 
Visceral adipose tissue: (VAT) - Total CSA  
• 
Subcutaneous adipose tissue (SAT) - Total CSA   
• 
Intermuscular adipose tissue (IMAT) - Total CSA 
• 
Visceral adipose tissue density: (VAT) - Average fat attenuation 
• 
Subcutaneous adipose tissue density (SAT) - Average fat 
attenuation 
• 
Intermuscular adipose tissue density (IMAT) - Average fat 
attenuation 
 
Semi-automated analysis 
• 
The semi-automated software recognizes muscle tissue based on 
attenuation (radiodensity) thresholds between −29 and +150 HU and 
provides an unbiased measurement of the skeletal muscle cross-
sectional area and muscle density (OsiriX Pixmeo SARL). (6) 
• 
Semi-automated primary adipose tissue readings are obtained at the L3 
level: VAT, SAT, IMAT. 
• 
All semi-automatic segmentation images will be reviewed for accuracy by 
two radiology investigators (LL and RB); all segmentation errors will be 
manually corrected, and cases with imaging artifacts excluded. 

 
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• 
Radiology reviewers will not have access to patient outcomes or patient 
height (needed for skeletal muscle index). 
• 
The following data form will be completed by the Radiology team for 
each patent: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• 
Semi-automated CT analysis feasibility of software validation are not 
needed as the software is already validated). 
 
Expertise of PIs: 
• 
Victor Chang, MD is Professor of Medicine at Rutgers New Jersey 
Medical School and Acting Chief of the Section of Hematology Oncology 
at the VA New Jersey Health Care System. His research is in symptom 
assessment and he is co-chair of the ECOG ACRIN NCORP Symptom 
Science and Treatment Toxicity Committee. 
• 
Robert Boutin, MD is Clinical Professor of Radiology at Stanford 
University School of Medicine. He specializes in musculoskeletal 
radiology and has written extensively on body composition CT. Dr. 
Boutin 
is 
Chair, 
Musculoskeletal 
Radiology 
Scientific 
Program 
Committee (2020-2023), Radiological Society of North America (RSNA) 
(1992 - Present)  
• 
Leon Lenchik, MD is Professor of Radiology at Wake Forest University 
School of Medicine, where he is Division Chief of Musculoskeletal 
Imaging, Vice Chair of Faculty Development, Department of Radiology 
and Co-Director of Bio-Imaging Resource Core, Older Americans 
Independence Center. Dr Lenchik has written extensively about muscle 
and fat imaging, and about bone radiography. 
 
S1505 Patient ID: _______ 
 
DATE central review completed (mm/dd/yyy): ____/_____/_______ 
 
EXAM DIAGNOSTIC at L3 level (without artifact): 
Yes 
No 
 
Muscle indices:  
• 
Skeletal muscle cross sectional area (CSA):    
____.____ cm2 
• 
Skeletal muscle density (SMD): ____.____ HU  
 
Fat indices:  
• 
Visceral adipose tissue (VAT):    ____.____ cm2   
• 
Subcutaneous adipose tissue (SAT):    ____.____ cm2 
• 
Intermuscular adipose tissue (IMAT):    ____.____ cm2 
• 
Visceral adipose tissue density (VATD):    
____.____ HU  
• 
Subcutaneous adipose tissue density (SATD):    ____.____ HU 
• 
Intermuscular adipose tissue density (IMATD):    ____.____ HU 
 

 
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d. 
Statistical Plan 
 
Summary statistics of the 9 muscle and adipose parameters (CSA, SMI, SMD, 
VAT, SAT, IMAT, VATD, SATD, IMATD) will be generated. (SMI will be 
calculated based on CSA and patient height.) 
 
The associations of these 9 parameters with baseline clinical (weight, body 
surface area, body mass index, ECOG PS) and laboratory variables 
(hemoglobin, albumin), and with weight loss during treatment will be estimated 
using linear regression. 
 
Associations of baseline CT measurements of muscle and adipose tissue with 
chemotoxicity incidence and OS will be estimated via logistic and Cox regression 
models, respectively.  Specific adverse event types of interest are listed above. 
 
Approximately 100 patients were eligible and evaluable for survival and toxicity 
outcomes. For simplicity of power calculations, we assume that the baseline CT 
measurements will be modeled as binary variables with values categorized as 
above vs below the median. This sample size provides at least 80% power to 
detect 16-28 percentage point differences between binomial proportions (e.g., 
1% vs 17%, 15% vs 40%, or 35% vs 63%), with a 2-sided alpha of 5%. One 
hundred patients also provide 80% power to detect a hazard ratio of 2 between 
median OS (e.g.,18 vs 36 months), based on a two-sample survival comparison 
with 2-sided alpha of 5%. 
 
Analyses will also be performed for the approximately 45 ineligible patients with 
evaluable outcomes, for exploratory purposes. 
 
Eligibility:  
 
Patients who participated in SWOG-1505. Baseline CT scans are submitted for 
central archiving. All 147 patients have submitted evaluable baseline scans.  
 
Clinical Endpoint(s) to be used in analyses: 
 
• 
Overall survival 
• 
Chemotherapy toxicity endpoints: Grade 3 or 4 neutropenia, febrile 
neutropenia, anemia, thrombocytopenia, sensory neuropathy, diarrhea, 
elevated ALT/AST, and weight loss during treatment. 
• 
Other clinical variables: Clinical (weight, body surface area, body mass 
index, ECOG PS) and laboratory variables (hemoglobin, albumin) at 
baseline; weight and body surface area at end of chemotherapy. 
 
e. 
Data Analysis 
 
CT scans are currently archived for all patient at Imaging and Radiation 
Oncology Core (IROC) at Ohio via TRIAD Imaging Submission. 
 
S1505 Archived images will be sent to: 
Dr.Boutin’s group at Stanford University School of Medicine, Stanford, CA. 
 
Images will be retrospectively reviewed by: 
Dr. Chang, Dr. Boutin, and Dr Lenchik 
 

 
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SWOG statisticians will perform the statistical analysis linking results with patient-
level data. 
 
f. 
Specimen Information 
 
CT scans are currently archived for all patient at Imaging and Radiation 
Oncology Core (IROC) at Ohio via TRIAD Imaging Submission. 

 
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g. 
References
 
1  
Bachmann J, Heiligensetzer M, Krakowski-Roosen H, et al. Cachexia worsens prognosis in 
patients with resectable pancreatic cancer. J Gastrointest Surg. 2008 Jul;12(7):1193-201. doi: 
10.1007/s11605-008-0505-z. Epub 2008 Mar 18. PubMed PMID: 18347879. 
 
2  
Lenchik L, Boutin RD. Sarcopenia: Beyond Muscle Atrophy and into the New Frontiers of 
Opportunistic Imaging, Precision Medicine, and Machine Learning. Semin Musculoskelet Radiol. 
2018 Jul;22(3):307-322. 
 
3 
Lenchik L, Lenoir KM, Tan J, Boutin RD, Callahan KE, Kritchevsky SB, Wells BJ. Opportunistic 
Measurement of Skeletal Muscle Size and Muscle Attenuation on Computed Tomography 
Predicts One-year Mortality in Medicare Patients. J Gerontol A Biol Sci Med Sci. 2018 Aug 16. 
doi: 10.1093/gerona/gly183. [Epub ahead of print] 
. 
4  
Boutin RD, Kritchevsky SB, Register TC, Wise BL, Bateni CP, Bayoumi A, Chen H, Chiles C, MD, 
Lenchik L. Low Paraspinous Muscle Attenuation on Computed Tomography (CT) Predicts All-
cause Mortality in the National Lung Screening Trial. Oral Presentation at the 103rd Scientific 
Assembly and Annual Meeting of the Radiological Society of North America. Chicago, IL, 
November 27, 2017 
 
5  
van Dijk DP, Bakens MJ, Coolsen MM, et al. Low skeletal muscle radiation attenuation and 
visceral adiposity are associated with overall survival and surgical site infections in patients with 
pancreatic 
cancer. 
J 
Cachexia 
Sarcopenia 
Muscle. 
2017 
Apr;8(2):317-326. 
doi: 
10.1002/jcsm.12155. Epub 2016 Oct. 
 
 
6  
Jin WH, Mellon EA, Frakes JM, Murimwa GZ, Hodul PJ, Pimiento JM, Malafa MP, Hoffe SE. 
Impact of sarcopenia in borderline resectable and locally advanced pancreatic cancer patients 
receiving stereotactic body radiation therapy. J Gastrointest Oncol. 2018 Feb;9(1):24-34. 
 
7  
van Dijk DP, Bakens MJ, Coolsen MM, et al. Low skeletal muscle radiation attenuation and 
visceral adiposity are associated with overall survival and surgical site infections in patients with 
pancreatic 
cancer. 
J 
Cachexia 
Sarcopenia 
Muscle. 
2017 
Apr;8(2):317-326. 
doi: 
10.1002/jcsm.12155. Epub 2016 Oct  
 
 
 
 
 
 
 

 
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18.3 
Instructions for the SWOG Specimen Bank 
 
The SWOG Biospecimen Bank receives, accessions, barcodes, and banks all formalin-
fixed, paraffin-embedded tissue blocks and unstained slides at room temperature.  
 
At the end of the study, the SWOG Statistical and Data Management Center (SDMC) will 
send the Bank a list of patients and specimens to distribute to Dr. Gregory Beatty. For 
each patient, 1 H&E stained slide will be scanned to a 20x digital image and saved to a 
hard drive, and 5 unstained positively charged slides (each at 5 microns thick) will be 
shipped for analysis. 
 

 
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Informed Consent Model for  S1505 
   
*NOTES FOR LOCAL INSTITUTION INFORMED CONSENT AUTHORS:  
 
This model informed consent form has been reviewed by the DCTD/NCI and is the official 
consent document for this study. Local IRB changes to this document are allowed.  (Institutions 
should attempt to use sections of this document that are in bold type in their entirety.)  Editorial 
changes to these sections may be made as long as they do not change information or intent.  If 
the institutional IRB insists on making deletions or more substantive modifications to the risks or 
alternatives sections, they may be justified in writing by the investigator and approved by the 
IRB.  Under these circumstances, the revised language, justification and a copy of the IRB 
minutes must be forwarded to the SWOG Operations Office for approval before a patient may be 
registered to this study.   
 
Please particularly note that the questions related to banking of specimens for future study 
are in bolded type and may not be changed in any way without prior approval from the 
SWOG Operations Office. 
Readability Statistics:   
 
Flesch Reading Ease  
60 (targeted above 55) 
Flesch-Kincaid Grade Level 8.8 (targeted below 8.5) 
 
• 
Instructions and examples for informed consent authors are in [italics].  
• 
A blank line,  __________, indicates that the local investigator should provide the 
appropriate information before the document is reviewed with the prospective 
research participant.  
• 
The term "study doctor" has been used throughout the model because the local 
investigator for a cancer treatment trial is a physician.   If this model is used for a 
trial in which the local investigator is not a physician, another appropriate term 
should be used instead of "study doctor".  
• 
The dates of protocol updates in the header and in the text of the consent is for 
reference to this model only and should not be included in the informed consent 
form given to the prospective research participant.  
• 
The local informed consent must state which parties may inspect the research 
records. This includes the NCI, the drug manufacturer for investigational studies, 
any companies or grantors that are providing study support (these will be listed in 
the protocol's model informed consent form) and SWOG.  
 
"SWOG" must be listed as one of the parties that may inspect the research records 
in all protocol consent forms for which patient registration is being credited to 
SWOG.  This includes consent forms for studies where all patients are registered 
directly through the SWOG Data Operations Office, all intergroup studies for 
which the registration is being credited to SWOG (whether the registration is 

 
S1505 
 
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through the SWOG Data Operations Office or directly through the other group), as 
well as consent forms for studies where patients are registered via CTSU and the 
registration is credited to SWOG. 
• 
When changes to the protocol require revision of the informed consent document, 
the IRB should have a system that identifies the revised consent document, in order 
to preclude continued use of the older version and to identify file copies.  An 
appropriate method to identify the current version of the consent is for the IRB to 
stamp the final copy of the consent document with the approval date.  The stamped 
consent document is then photocopied for use.  Other systems of identifying the 
current version of the consent such as adding a version or approval date are allowed 
as long as it is possible to determine during an audit that the patient signed the most 
current version of the consent form.  
 
*NOTES FOR LOCAL INVESTIGATORS:  
• 
The goal of the informed consent process is to provide people with sufficient 
information for making informed choices about participating in research.   The 
consent form provides a summary of the study, the individual's rights as a study 
participant, and documents their willingness to participate.  The consent form is, 
however, only one piece of an ongoing exchange of information between the 
investigator and study participant.  For more information about informed consent, 
review the "Recommendations for the Development of Informed Consent 
Documents for Cancer Clinical Trials" prepared by the Comprehensive Working 
Group on Informed Consent in Cancer Clinical Trials for the National Cancer 
Institute.  The Web site address for this document is 
http://cancer.gov/clinicaltrials/understanding/simplification-of-informed-consent-
docs/ 
• 
Suggestion for Local Investigators:  An NCI pamphlet explaining clinical trials is 
available for your patients.  The pamphlet is titled: "Taking Part in Cancer 
Treatment Research Studies".  This pamphlet may be ordered on the NCI Web site 
at https://cissecure.nci.nih.gov/ncipubs or call 1-800-4- CANCER (1-800-422-
6237) to request a free copy.  
• 
Optional feature for Local Investigators: Reference and attach drug sheets, 
pharmaceutical information for the public, or other material on risks.  Check with 
your local IRB regarding review of additional materials. 
 
*These notes for authors and investigators are instructional and should not be included in the 
informed consent form given to the prospective research participant. 

 
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Consent Form 
 
Study Title for Study Participants: Testing two approved chemotherapy 
combinations before and after surgery for pancreatic cancer 
 
Official Study Title for Internet Search on http://www.ClinicalTrials.gov: 
S1505, “A Randomized Phase II Study of Perioperative mFOLFIRINOX versus 
Gemcitabine/nab-Paclitaxel as Therapy for Resectable Pancreatic 
Adenocarcinoma.” 
 
What is the usual approach to my resectable pancreatic cancer?  
 
You are being asked to take part in this study because you have pancreatic cancer that can be 
removed by surgery. People who are not in a study are usually treated with surgery first and then 
with chemotherapy drugs approved by the Food and Drug Administration (FDA). Sometimes 
radiation is also used and your doctor can explain which may be best for you. For patients who 
receive the usual approach for this cancer, about 20 out of 100 are cancer-free at five years.  
 
What are my other choices if I do not take part in this study? 
 
If you decide not to take part in this study, you have other choices. For example: 
• you may choose to have the usual approach described above 
• you may choose to take part in a different study, if one is available 
• or you may choose not to be treated for cancer, but you may want to receive comfort 
care to relieve symptoms. 
 
Why is this study being done? 
 
The purpose of this study is to compare the effects of two different combinations of FDA-
approved chemotherapy drugs. These two combinations are called mFOLFIRINOX (oxaliplatin, 
irinotecan, and fluorouracil) and gemcitabine plus nab-paclitaxel. These chemotherapy drugs will 
be given before and after surgery. The addition of these chemotherapy drugs before surgery is a 
new approach that is being tested in this study. This new approach could prevent your cancer 
from returning, but it could also cause side-effects. This study will allow the researchers to know 
if it is a good idea to treat pancreatic cancer with chemotherapy drugs before surgery, and if so, 
to see which of the two drug combinations is better. To be better, the study approach should 
increase the number of people alive at 2 years from about 40% with the usual approach to about 
58% with the newer approach. There will be about 150 people taking part in this study. (05/9/17) 
 

 
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What are the study groups? 
 
This study has two study groups. 
• Group 1 will get the drug combination mFOLFIRINOX (5-fluorouracil, irinotecan, 
oxaliplatin) given through a vein on Day 1 and 15 of every 28-day cycle. Fluorouracil 
is given continuously on Days 1-3 and 15-17 of each cycle. After 3 cycles of 
treatment (about 3 months), you will have a recovery period of about 1 month, and 
then you will have surgery to remove your cancer. Then 4-8 weeks after surgery, you 
will begin another 3 cycles of mFOLFIRINOX on the same schedule. 
• Group 2 will get the drug combination of gemcitabine and nab-paclitaxel through a 
vein on Days 1, 8, and 15 of every 28-day cycle. After 3 cycles of treatment (about 3 
months), you will have a recovery period of about 1 month, and then you will have 
surgery to remove your cancer. Then 4-8 weeks after surgery, you will begin another 
3 cycles of gemcitabine and nab-paclitaxel on the same schedule. 
 
Below is a timeline for patient treatment during the study.   
 
3 months 
Up to 4 weeks 
4 to 8 weeks 
3 months 
Chemotherapy treatment 
Group 1: On Days 1 and 
15 of each 28 day cycle 
for 3 cycles. 
Group 2: On Days 1, 8, 
& 15 of each 28 day 
cycle for 3 cycles 
Both groups: 
Undergo surgery 
after completion 
of Cycle 3 
 
Both groups: 
Recovery after 
surgery, 
timeframe will 
vary by patient 
 
Chemotherapy treatment 
Group 1: On Days 1 and 
15 of each 28 day cycle 
for 3 cycles. 
Group 2: On Days 1, 8, 
& 15 of each 28 day 
cycle for 3 cycles 
 
 
A computer will by chance assign you to treatment groups in the study.  This is called 
randomization.  This is done by chance because no one knows if one study group is better or 
worse than the others.  
 
Another way to find out what will happen to you during this study is to read the chart below. 
Start reading at the left side and read across to the right, following the lines and arrows. 
 
 
 
 
Randomize 
(The computer will 
randomly put you in a 
study group) 
Group 2 
Gemcitabine/nab-
paclitxael + Surgery + 
Gemcitabine/nab-
paclitaxel 
You agree to 
take part in the 
study 
Group 1 
mFOLFIRINOX + 
Surgery + 
mFOLFIRINOX 

 
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How long will I be in this study? 
You will receive the study treatment for up to 8 months. After you finish study treatment, your 
doctor will continue to watch you for side effects and follow your condition for four years. 
 
What extra tests and procedures will I have if I take part in this study? 
The exams, tests, and procedures you will have are part of the usual approach for your cancer. 
Therefore, there are not any extra exams and tests that you will need to have if you take part in 
this study. 
 
What possible risks can I expect from taking part in this study? 
If you choose to take part in this study, there is a risk that: 
• You may lose time at work or home and spend more time in the hospital or doctor’s 
office than usual 
• You may be asked sensitive or private questions which you normally do not discuss 
• The study approach may not be better, and could possibly be worse, than the usual 
approach for your cancer. 
• The study approach of chemotherapy before surgery may prevent you from getting 
the surgery if your cancer continues to grow during chemotherapy 
• The study approach of adding combination chemotherapy before surgery may 
result in increased side-effects from the surgery 
 
The chemotherapy and surgery used in this study may affect how different parts of your 
body work such as your liver, kidneys, heart, and blood. The study doctor will be testing 
your blood and will let you know if changes occur that may affect your health. 
 
There is also a risk that you could have side effects from the study drug(s)/study approach. 
 
Here are important points about side effects: 
• The study doctors do not know who will or will not have side effects. 
• Some side effects may go away soon, some may last a long time, or some may never 
go away. 
• Some side effects may interfere with your ability to have children. 
• Some side effects may be serious and may even result in death. 
 
Here are important points about how you and the study doctor can make side effects less of 
a problem: 
• Tell the study doctor if you notice or feel anything different so they can see if you 
are having a side effect. 
• The study doctor may be able to treat some side effects. 
• The study doctor may adjust the study drugs to try to reduce side effects. 
 
The tables below show the most common and the most serious side effects that researchers 
know about. There might be other side effects that researchers do not yet know about. If 
important new side effects are found, the study doctor will discuss these with you.  

 
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Study Group 1 - Possible Side Effects of mFOLFIRINOX (5-Fluorouracil, Irinotecan, 
and Oxaliplatin) 
 
COMMON, SOME MAY BE SERIOUS 
In 100 people receiving mFOLFIRINOX (5-Fluorouracil, Irinotecan, and Oxaliplatin),  
more than 20 and up to 100 may have: 
• Severe diarrhea 
• Constipation, nausea, vomiting, diarrhea, loss of appetite 
• Weakness 
• Infection, especially when white blood cell count is low 
• Hair loss 
• Loss of appetite, weight loss 
• Anemia which may require a blood transfusion 
• Fever, pain 
• Dizziness, tiredness 
• Cough, shortness of breath 
• Rash, increased risk of sunburn, itching 
• Bruising, bleeding 
• Sores in mouth which may cause difficulty swallowing 
• Redness, pain or peeling of palms and soles 
• Numbness and tingling of the arms and legs 
• Feeling of "pins and needles" in arms and legs 
• Heartburn 
• Headache 

 
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OCCASIONAL, SOME MAY BE SERIOUS 
In 100 people receiving mFOLFIRINOX (5-Fluorouracil, Irinotecan, and Oxaliplatin),  
from 4 to 20 may have: 
• A tear or hole in internal organs that may require surgery 
• Allergic reaction which may cause rash, low blood pressure, wheezing, shortness of 
breath, swelling of the face or throat 
• Blood clot which may cause swelling, pain, shortness of breath 
• Scarring of the lungs 
• Chest pain 
• Abnormal heartbeat which may cause fainting 
• Hoarseness 
• Abnormal eye movement, watering eyes, discomfort from light, blurred vision with 
chance of blindness 
• Swelling and redness of the eye 
• Problem with eyelid 
• Hearing loss 
• Dry eye, mouth, skin 
• Fluid in the belly 
• Difficulty walking, opening mouth, talking, with balance and hearing, smelling, eating, 
sleeping, emptying the bladder 
• Swelling of the body which may cause shortness of breath 
• Blockage of the airway which may cause shortness of breath, cough, wheezing 
• Bleeding from multiple sites including vaginal bleeding, bleeding of the testis, or 
bleeding of the brain 
• Internal bleeding which may cause black tarry stool, blood in vomit or urine, or 
coughing up blood 
• Damage to organs which may cause shortness of breath 
• Chills 
• Swelling and redness at the site of the medication injection 
• Liver damage which may cause yellowing of eyes and skin 
• Kidney damage which may require dialysis 
• Weight gain, dehydration, passing gas 
• Changes in taste, voice 
• Stroke which may cause paralysis, weakness 
• Inability to move shoulder or turn head 
• Muscle weakness 
• Seizure 
• Worry, confusion, depression 
• Increased urination 
• Stuffy nose, hiccups, sinus problems 
• Increased sweating, flushing, hot flashes 
• High blood pressure 
• Low blood pressure which may cause feeling faint 

 
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RARE, AND SERIOUS 
In 100 people receiving mFOLFIRINOX (5-Fluorouracil, Irinotecan, and Oxaliplatin),  
3 or fewer may have: 
• A new cancer resulting from treatment of earlier cancer 
• Brain damage, Reversible Posterior Leukoencephalopathy Syndrome, which may 
cause headache, seizure, blindness 
 
 
Study Group 2 - Possible Side Effects of Gemcitabine  
COMMON, SOME MAY BE SERIOUS 
In 100 people receiving Gemcitabine, more than 20 and up to 100 may have: 
• Flu-like symptoms of muscle pain, fever, headache, chills and fatigue 
• Nausea, vomiting 
• Rash 
• Hair loss 
• Infection, especially when white blood cell count is low 
• Bruising, bleeding 
• Anemia which may  require a blood transfusion 
• Muscle weakness 
• Blood in urine 
• Feeling of "pins and needles" in arms and legs 
• Numbness and tingling of the arms and legs 
• Tiredness 
• Difficulty sleeping 
• Hearing loss 
• Swelling of arms, legs 
 
OCCASIONAL, SOME MAY BE SERIOUS 
In 100 people receiving Gemcitabine, from 4 to 20 may have: 
• Diarrhea, constipation 
• Sores in mouth which may cause difficulty swallowing 
• Shortness of breath 
• Fluid in the organs which may cause low blood pressure, shortness of breath, swelling 
of ankles 
• Brain damage, Reversible Posterior Leukoencephalopathy Syndrome, which may 
cause headache, seizure, blindness 

 
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RARE, AND SERIOUS 
In 100 people receiving Gemcitabine, 3 or fewer may have: 
• Abnormal heartbeat 
• Heart failure or heart attack which may cause shortness of breath, swelling of ankles, 
and tiredness 
• Blisters on the skin 
• Sores on the skin 
• Blood clot 
• Liver damage which may cause yellowing of eyes and skin, swelling 
• Damage to organs which may cause shortness of breath 
• Allergic reaction which may cause rash, low blood pressure, wheezing, shortness of 
breath, swelling of the face or throat 
• Kidney damage which may require dialysis 
• Scarring of the lungs 
• Fluid around lungs 
• Blockage of the airway which may cause cough 
 
Study Group 2 – Possible Side Effects of nab-Paclitaxel  
COMMON, SOME MAY BE SERIOUS 
In 100 people receiving nab-Paclitaxel, more than 20 and up to 100 may have: 
• Anemia, which may cause tiredness, or may require blood transfusions 
• Infection, especially when white blood cell count is low 
• Diarrhea, nausea 
• Pain 
• Numbness and tingling of the arms and legs 
• Tiredness 
• Hair loss 
 
OCCASIONAL, SOME MAY BE SERIOUS 
In 100 people receiving nab-Paclitaxel, from 4 to 20 may have: 
• Abnormal heartbeat 
• Heart stops beating 
• Cloudiness of the eye, visual disturbances 
• Vomiting 
• Swelling of the body 
• Allergic reaction which may cause rash, low blood pressure, wheezing, shortness of 
breath, swelling of the face or throat 
• Mini stroke 
• Paralysis, weakness, headache 
• Stroke 
• Blood clot which may cause swelling, pain, shortness of breath 
• Hoarseness 

 
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RARE, AND SERIOUS 
In 100 people receiving nab-Paclitaxel, 3 or fewer may have: 
• Bruising, bleeding 
• Lung collapse which may cause chest pain 
 
Study Group 1 and 2 – Possible Side Effects of Surgery 
 
OCCASIONAL, SOME MAY BE SERIOUS 
In 100 people receiving surgery, from 4 to 20 may have: 
• Leakage around site of pancreatic repair  
• Infection inside the belly 
• Infection at the surgical incision 
• Pneumonia 
• Digestive problems related to food passage through stomach 
 
RARE, AND SERIOUS 
In 100 people receiving surgery, 3 or fewer may have: 
• Leakage of bile inside the belly 
• Post-operative bleeding requiring blood transfusion 
• Blood clot which may cause swelling, pain, shortness of breath  
 
 
Let your study doctor know of any questions you have about possible side effects. You can 
ask the study doctor questions about side effects at any time. 
 
Reproductive risks: You should not get pregnant, breastfeed, or father a baby while in this 
study. The chemotherapy drugs used in this study could be very damaging to an unborn 
baby. Check with the study doctor about what types of birth control, or pregnancy 
prevention, to use while in this study and for three months after the last dose of 
chemotherapy. 
 
 
What possible benefits can I expect from taking part in this study? 
 
It is not possible to know at this time if the study approach is better than the usual approach so 
this study may or may not help you. This study will help researchers learn things that will help 
people in the future. 
 

 
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Can I stop taking part in this study? 
 
Yes. You can decide to stop at any time. If you decide to stop for any reason, it is important to let 
the study doctor know as soon as possible so you can stop safely. If you stop, you can decide 
whether or not to let the study doctor continue to provide your medical information to the 
organization running the study. 
 
The study doctor will tell you about new information or changes in the study that may affect 
your health or your willingness to continue in the study. 
 
The study doctor may take you out of the study: 
• If your health changes and the study is no longer in your best interest 
• If new information becomes available 
• If you do not follow the study rules 
• If the study is stopped by the sponsor, IRB or FDA. 
 
What are my rights in this study? 
 
Taking part in this study is your choice. No matter what decision you make, and even if your 
decision changes, there will be no penalty to you. You will not lose medical care or any legal 
rights. 
 
For questions about your rights while in this study, call the ________________________ (insert 
name of center) Institutional Review Board at __________________ (insert telephone number). 
(Note to Local Investigator: Contact information for patient representatives or other individuals 
at a local institution who are not on the IRB or research team but take calls regarding clinical 
trial questions can also be listed here.) 
 
What are the costs of taking part in this study? 
 
You and/or your health plan/insurance company will need to pay for all of the costs of treating 
your cancer while in this study, including the cost of tests, procedures, or medicines to manage 
any side effects, unless you are told that certain tests are supplied at no charge. Before you 
decide to be in the study, you should check with your health plan or insurance company to find 
out exactly what they will pay for. 
 
You will not be paid for taking part in this study. 
 
What happens if I am injured or hurt because I took part in this study? 
 
If you are injured or hurt as a result of taking part in this study and need medical treatment, 
please tell your study doctor. The study sponsors will not offer to pay for medical treatment for 
injury.  Your insurance company may not be willing to pay for study-related injury.  If you have 
no insurance, you would be responsible for any costs.

 
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If you feel this injury was a result of medical error, you keep all your legal rights to receive 
payment for this even though you are in a study. 
 
Who will see my medical information? 
 
Your privacy is very important to us and the researchers will make every effort to protect it. 
Your information may be given out if required by law. For example, certain states require 
doctors to report to health boards if they find a disease like tuberculosis. However, the 
researchers will do their best to make sure that any information that is released will not identify 
you. Some of your health information, and/or information about your specimen, from this study 
will be kept in a central database for research. Your name or contact information will not be put 
in the database. 
 
There are organizations that may inspect your records. These organizations are required to make 
sure your information is kept private, unless required by law to provide information. Some of 
these organizations are: 
• The study sponsor (SWOG) 
• The Institutional Review Board, IRB, is a group of people who review the research with 
the goal of protecting the people who take part in the study. 
• The Food and Drug Administration and the National Cancer Institute in the U.S., and 
similar ones if other countries are involved in the study. 
 
Where can I get more information? 
 
You may visit the NCI Web site at http://cancer.gov/ for more information about studies or 
general information about cancer. You may also call the NCI Cancer Information Service to get 
the same information at: 1-800-4-CANCER (1-800-422-6237). 
 
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 21CFR50.25 (c) and must be included verbatim in all informed consent documents. The 
text in this paragraph cannot be revised.] 
 
Who can answer my questions about this study? 
 
You can talk to the study doctor about any questions or concerns you have about this study or to 
report side effects or injuries. Contact the study doctor __________________ (insert name of 
study doctor[s]) at __________________ (insert telephone number). 

 
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ADDITIONAL STUDIES SECTION:  
This section is about optional studies you can choose to take part in 
 
This part of the consent form is about optional studies that you can choose to take part in. You 
will not get health benefits from any of these studies. The researchers leading this optional study 
hope the results will help other people with cancer in the future. 
 
The results will not be added to your medical records and you or your study doctor will not know 
the results. 
 
You will not be billed for these optional studies. You can still take part in the main study even if 
you say ‘no’ to any or all of these studies. If you sign up for but cannot complete any of the 
studies for any reason, you can still take part in the main study. 
 
Circle your choice of “yes” or “no” for each of the following studies. 
 
Optional Sample Collection for Biobanking for Possible Future Studies 
 
Researchers are trying to learn more about cancer, diabetes, and other health problems. Much of 
this research is done using samples from your tissue, blood, urine, or other fluids. Through these 
studies, researchers hope to find new ways to prevent, detect, treat, or cure health problems. 
 
Some of these studies may be about genes. Genes carry information about features that are found 
in you and in people who are related to you. Researchers are interested in the way that genes 
affect how your body responds to treatment. 
 
If you choose to take part, tissue from your surgery will be collected. The researchers ask your 
permission to store and use your samples and related health information (for example, your 
response to cancer treatment, results of study tests and medicines you are given) for medical 
research. The research that may be done is unknown at this time. Storing samples for future 
studies is called “biobanking”. The Biobank is being run by SWOG and supported by the 
National Cancer Institute. 
 
WHAT IS INVOLVED? 
If you agree to take part, here is what will happen next: 
1) A sample from the tissue will be collected at the time of your surgery will be sent to 
the Biobank.  
a) Your sample and some related health information may be stored in the Biobank, 
along with samples and information from other people who take part. The 
samples will be kept until they are used up. Information from your medical record 
will be updated from time to time. 
2) Qualified researchers can submit a request to use the materials stored in the Biobanks. 
A science committee at the clinical trials organization, and/or the National Cancer 

 
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3) Institute, will review each request. There will also be an ethics review to ensure that 
the request is necessary and proper. Researchers will not be given your name or any 
other information that could directly identify you.  
4) Neither you nor your study doctor will be notified when research will be conducted or 
given reports or other information about any research that is done using your samples.  
5) Some of your genetic and health information may be placed in central databases that 
may be public, along with information from many other people. Information that 
could directly identify you will not be included. 
 
WHAT ARE THE POSSIBLE RISKS? 
1) There is a risk that someone could get access to the personal information in your 
medical records or other information researchers have stored about you. 
2) There is a risk that someone could trace the information in a central database back to 
you. Even without your name or other identifiers, your genetic information is unique 
to you. The researchers believe the chance that someone will identify you is very 
small, but the risk may change in the future as people come up with new ways of 
tracing information. 
3) In some cases, this information could be used to make it harder for you to get or keep 
a job or insurance. There are laws against the misuse of genetic information, but they 
may not give full protection. There can also be a risk in knowing genetic information. 
New health information about inherited traits that might affect you or your blood 
relatives could be found during a study. The researchers believe the chance these 
things will happen is very small, but cannot promise that they will not occur. 
 
HOW WILL INFORMATION ABOUT ME BE KEPT PRIVATE? 
Your privacy is very important to the researchers and they will make every effort to protect it. 
Here are just a few of the steps they will take: 
1) When your sample(s) is sent to the researchers, no information identifying you (such 
as your name) will be sent. Samples will be identified by a unique code only.  
2) The list that links the unique code to your name will be kept separate from your 
sample and health information. Any Biobank and SWOG staff with access to the list 
must sign an agreement to keep your identity confidential. 
3) Researchers to whom SWOG sends your sample and information will not know who 
you are. They must also sign an agreement that they will not try to find out who you 
are. 
4) Information that identifies you will not be given to anyone, unless required by law. 
5) If research results are published, your name and other personal information will not 
be used. 

 
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WHAT ARE THE POSSIBLE BENEFITS? 
You will not benefit from taking part.  The researchers, using the samples from you and others, 
might make discoveries that could help people in the future. 
 
ARE THERE ANY COSTS OR PAYMENTS? 
There are no costs to you or your insurance. You will not be paid for taking part. If any of the 
research leads to new tests, drugs, or other commercial products, you will not share in any 
profits. 
 
WHAT IF I CHANGE MY MIND? 
If you decide you no longer want your samples to be used, you can call the study doctor, 
_________________, (insert name of study doctor for main trial) at 
________________________ (insert telephone number of study doctor for main trial) who will 
let the researchers know. Then, any sample that remains in the bank will no longer be used and 
related health information will no longer be collected. Samples or related information that have 
already been given to or used by researchers will not be returned. 
 
WHAT IF I HAVE MORE QUESTIONS? 
If you have questions about the use of your samples for research, contact the study doctor, 
________________, (insert name of study doctor for main trial), at _____________________ 
(insert telephone number of study doctor for main trial). 
 
Please circle your answer to show whether or not you would like to take part in each option:  
 
SAMPLES FOR FUTURE RESEARCH STUDIES: 
 
My samples and related information may be kept in a Biobank for use in future 
health research. 
 
 
YES 
 
NO 
 
Future Contact: 
I agree to allow my study doctor, or someone approved by my study doctor, to 
contact me regarding future research involving my participation in this study.  
Yes 
No 
 

 
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My Signature Agreeing to Take Part in the Main Study 
 
I have read this consent form or had it read to me. I have discussed it with the study doctor and 
my questions have been answered. I will be given a signed copy of this form. I agree to take part 
in the main study and any additional studies where I circled ‘yes’.  
 
Participant’s signature________________________________ 
 
Date of signature_____________________________________ 
 
 
(The following signature and date lines for the person(s) conducting the discussion may be 
included at the discretion of the study sponsor.) 
 
Signature of person(s) conducting the informed consent 
discussion___________________________________ 
 
Date of signature_____________________________________ 
 
 

 
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Specimen Consent Supplemental Sheets 
 
How are Specimens Used for Research? 
 
Where do specimens come from? 
 
A specimen may be from a blood sample or from bone marrow, skin, toenails or other body materials.  
People who are trained to handle specimens and protect donors' rights make sure that the highest 
standards of quality control are followed by SWOG.  Your doctor does not work for SWOG, but has 
agreed to help collect specimens from many patients.  Many doctors across the country are helping in the 
same way.   
 
Why do people do research with specimens? 
 
Research with specimens can help to find out more about what causes cancer, how to prevent it, how to 
treat it, and how to cure it.  Research using specimens can also answer other health questions.  Some of 
these include finding the causes of diabetes and heart disease, or finding genetic links to Alzheimer's. 
 
What type of research will be done with my specimen? 
 
Many different kinds of studies use specimens.  Some researchers may develop new tests to find 
diseases.  Others may develop new ways to treat or even cure diseases.  In the future, some of the 
research may help to develop new products, such as tests and drugs.  Some research looks at diseases 
that are passed on in families (called genetic research).  Research done with your specimen may look for 
genetic causes and signs of disease. 
 
How do researchers get the specimen? 
 
Researchers from universities, hospitals, and other health organizations conduct research using 
specimens.  They contact SWOG and request samples for their studies.  SWOG reviews the way that 
these studies will be done, and decides if any of the samples can be used. SWOG gets the specimen and 
information about you from your hospital, and sends the specimen samples and some information about 
you to the researcher.  SWOG will not send your name, address, phone number, social security number 
or any other identifying information to the researcher. 
 
Will I find out the results of the research using my specimen? 
 
You will not receive the results of research done with your specimen.  This is because research can take 
a long time and must use specimen samples from many people before results are known.  Results from 
research using your specimen may not be ready for many years and will not affect your care right now, 
but they may be helpful to people like you in the future. 
 
Why do you need information from my health records? 
 
In order to do research with your specimen, researchers may need to know some things about you.  (For 
example:  Are you male or female?  What is your race or ethnic group? How old are you?  Have you ever 
smoked?)  This helps researchers answer questions about diseases.  The information that will be given to 
the researcher may include your age, sex, race, diagnosis, treatments and family history.  This 
information is collected by your hospital from your health record and sent to SWOG.  If more information 
is needed, SWOG will send it to the researcher. 

 
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Will my name be attached to the records that are given to the researcher? 
 
No.  Your name, address, phone number and anything else that could identify you will be removed before 
they go to the researcher.  The researcher will not know who you are. 
 
How could the records be used in ways that might be harmful to me? 
 
If your confidential genetic information is discovered, you may suffer from genetic discrimination. Genetic 
discrimination occurs if people are treated unfairly because of differences in their genes that increase 
their chances of getting a certain disease. In the past, this could have resulted in the loss of health 
insurance or employment. Because of this, The Genetic Information Nondiscrimination Act of 2008, also 
referred to as GINA, was passed by Congress to protect Americans from such discrimination. The new 
law prevents discrimination from health insurers and employers. This act was signed into federal law on 
May 21, 2008, and went into effect May 2009. This law does not cover life insurance, disability insurance 
and long-term care insurance. 
 
While this study has safeguards in place to protect your confidential genetic information and to make it 
extremely unlikely that your identity would be connected with any special studies that are performed on 
your tissue, it is possible that this information could be discovered by someone who is unauthorized to 
have access to it. 
 
How am I protected? 
 
SWOG is in charge of making sure that information about you is kept private.  SWOG will take careful 
steps to prevent misuse of records.  Your name, address, phone number and any other identifying 
information will be taken off anything associated with your specimen before it is given to the researcher.  
This would make it very difficult for any research results to be linked to you or your family.  Also, people 
outside the research process will not have access to results about any one person which will help to 
protect your privacy. 
 
What if I have more questions? 
 
If you have any questions, please talk to your doctor or nurse, or call our research review board at (Insert 
IRB's Phone Number).