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FOR GROUP MEETING

OCTOBER 8-10, 2002

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Gastrointestinal Program

The GI program had a productive year in 2002 thanks to your efforts and the hard work of the personnel at the research base. Our total accrual including registrations for intergroup trials chaired by NCCTG was 1048 for treatment trials and 439 for translational trials for the last 12 months. We opened 2 trials and closed 6 trials during the year. There are 8 studies currently in development. All 11 of the ASCO/AACR abstracts that we submitted for the 2002 meetings were accepted for presentation. In charting the momentum for our program we remain on a very positive trajectory.

Colorectal/Anal Cancer Program:

Adjuvant Studies: The CALGB led Stage II study (C9581) of no treatment versus

17-1A monoclonal antibody closed in July. We contributed about 263 of the 2000 patients enrolled. A successor trial for Stage II patients is in development by ECOG. The current concept includes enrollment of 3100 patients with mandatory tissue submission and real time testing for MSI and 18q allelic deletion. Patients deemed to be at high-risk are randomized to 5-FU/LV +/- a signal transduction inhibitor. Plans to use Iressa were derailed by the negative data in combination with chemotherapy that came from trials done in non small cell lung cancer. In this study the low-risk patients will be followed for recurrence and survival. The Stage III trial (C89803) of the Saltz regimen versus 5-FU/leucovorin is maturing. NCCTG is leading the next Stage III adjuvant trial of 5-FU/LV administered as an infusion plus either oxaliplatin or CPT-11. Since the last meeting a third arm of 12 weeks of FOLFOX plus 12 weeks of FOLFIRI has been added. Tissue and blood will be requested from all patients. The NCI has developed a position paper on this issue that will be made public soon. At least some NCCTG sites will be asked to collect frozen tissue for analysis using microarray technology in this trial. The use of rofecoxib versus placebo after completion of adjuvant therapy in patients with Stages II and III colon cancer is the subject of the VICTOR trial for which we will be the US coordinating site. The QUASAR group from England is the lead group on this trial. We anticipate that this trial will open in early 2003. Two rectal neo/adjuvant studies are planned. Patients treated preoperatively will be randomized to capecitabine versus infusion of 5-FU. The original study design also called for a second randomization to erythropoietin or placebo which may or may not be included in the final design. After surgery patients will be eligible for a second trial, regardless of whether or not preoperative chemotherapy and radiation was given. The randomization in this study is to one of three arms: 5-FU/LV +/- CPT-11 or oxaliplatin. If postoperative radiation is needed it will be provided. A concept will be discussed at the meeting for an NCCTG only trial of capecitabine plus celecoxib plus radiation as adjuvant therapy to be done in lieu of particiaption in the NSABP study. In the setting of resectable colorectal cancer metastatic only to the liver NCCTG is leading a

collaboration with the NSABP on a Phase II trial (N9945) of intraarterial FUDR, oxaliplatin + capecitabine. Because of tissue considerations, patients need to be enrolled before surgery. Subsequently, a randomized Phase III trial of capecitabine + oxaliplatin +/- intraarterial FUDR with NSABP as the lead group is planned. NSABP wants to deviate from our study design by eliminating the fifth week, a week of rest with no treatment administered in each cycle. At the meeting we will discuss the merits of this and whether or not to add a cohort of 15-20 patients

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using this more intensive scehdule in order to collect some pilot tolerability data for the

modification. The RTOG led trial of 5-FU + either mitomycin or cisplatin with radiation in anal cancer remains open with modest NCCTG accrual to date.

Advanced Disease:

The three arm study (N9741) of the Saltz regimen versus oxaliplatin + 5-FU/leucovorin versus oxaliplatin + CPT-11 for first-line therapy is closed to new patients and resulted in considerable attention for the group at ASCO. The blood samples and QOL data are being analyzed. We hope to have a manuscript ready for submission by early 2003. The data from N9741 were used to support the NDA for oxaliplatin that was approved by the FDA for second line therapy in August of 2002. A replacement randomized Phase III trial for previously untreated patients will randomize patients between 5-FU/LV plus oxaliplatin or capecitabine plus oxaliplatin plus or minus OSI-774 in a 2x2 randomization scheme.

The second-line study (N9841) of CPT-11 versus 5-FU/leucovorin + oxaliplatin with cross over to the other arm upon progression, is accruing more slowly than we had hoped. About 420 of 550 patients needed are on study. It is unclear if the approval of oxaliplatin for second line therapy will affect accrual to N9841 in a positive or negative manner. Two additional treatment programs in N0048 for patients progressing after oxaliplatin/5-FU/LV using CPT-11 or after CPT-11 + oxaliplatin using 5-FU/LV are accruing more slowly than expected as well.

The study of FOLFOX + C225 for non-optimally resectable liver-limited recurrent colon cancer is nearly ready for activation. Contract issues and the final NCI approval are in progress.

Translational and Record Studies: Dr. Thibodeau (98-46-54) and Dr. Witzig (95-04-52) are

both working on analyses of the data culled from the blocks for their respective studies on chromosomal and flow cytometric analyses and manuscripts are in various phases of preparation. In addition a manuscript has been submitted to the NEJM from NCCTG and Dr. Steven Gallinger’s lab at the University of Toronto showing that patients whose tumors show high levels of microsatellite instability are actually adversely affected when given 5-FU based adjuvant chemotherapy. Tim Hobday will be writing a manuscript on his review from the NCCTG database exploring the characteristics of patients entered on our studies for advanced colorectal cancer who survived more than 5 years after diagnosis of advanced disease.

Upper Gastrointestinal Cancer Program:

Gastroesophageal Cancer: The GI intergroup is piloting several approaches that we expect to culminate in an adjuvant trial to open in 2003. The trial of paclitaxel, 5-FU and cisplatin with radiation and amifostine (N0044) is open. Pharmacogenomic analysis in collaboration with Dr. Howard Mcleod from Washington University will be a part of this study. Toxicity led to temporary suspension of this trial with dose modifications adopted to enhance tolerability. The advanced esophageal and gastroesophageal junction cancer trial (N9941) of taxotere and CPT-11 is complete and a manuscript has been submitted for publication. A replacement study of

oxaliplatin and capecitabine (N0149) is in development and should be activated by the time of this publication. The study of CPT-11 in gastric cancer (96-41-52) met its accrual goal with 68

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enrolled patients on study. This study is being analyzed and the translational studies are in progress so that an ASCO abstract can be submitted for 2003. A follow up study of capecitabine plus taxotere is in development. N0242, A Phase II Study of Docetaxel and Capecitabine in Patients with Measurable Metastatic Adenocarcinoma of the Stomach and Gastroesophageal Junction Is also in development.

Pancreatic Cancer: A manuscript on the pilot trial (96-43-52) in locally advanced

pancreas/gastric cancer study with gemcitabine plus cisplatin radiosensitization has been submitted. Accrual on the Phase II study successor trial is underway. Four cycles of gemcitabine post radiation are incorporated in the Phase II trial. A manuscript on the oxaliplatin + gemcitabine trial (98-43-51) in advanced disease is in preparation. The trial evaluating a regimen of gemcitabine plus ISIS 2503 (N0043) is also nearly ready for analysis. The next generation advanced pancreatic cancer study will randomize patients to gemcitabine plus the proteosome inhibitor PS-341 or to PS341 followed by the addition of gemcitabine to that drug at the time of progression on the single agent drug (N014C). The opening of that study depends on the determination of the final Phase II dose from a phase I trial that is being completed at Dana Farber Cancer Center.

Hepatobiliary cancer: The gemcitabine + docetaxel for primary hepatocellular cancer (N0041) trial is reopened after a dose adjustment. Accrual has been slow. The 5-FU/leucovorin + gemcitabine (N0042) study for gall bladder and bile duct cancers will be analyzed for an ASCO 2003 submission. The study of Alimta + Gemcitabine for gallbladder and biliary cancer is nearing finalization (N9943).

Goals for the near future include: identifying active regimens for phase II testing based on preclinical leads identified in collaboration with the Novel Therapeutics Committee and maintaining a strong record of accrual. The integration of translational studies whenever appropriate and incorporation of QOL measures into trials are also priorities.

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Program Status Reports for GASTROINTESTINAL - October 2002

Table of Contents - Page 1 of 5

GI NCCTG GI Committee

Lower GI

974651 A Phase II Study of Patients With Unresectable Hepatic Metastases fromMetastatic Adenocarcinoma of the Colon or Rectum

C9581 Phase III Randomized Study of Adjuvant Immunotherapy With Mono-clonalAntibody 17-1A Versus No Adjuvant Therapy Following Resec-tion forStage II (Modified Astler-Coller B2) Adenocarcinoma of the Colon

N0048 Phase II Studies of Irinotecan (CPT-11) or 5-Fluorouracil(5-FU)/Leuco-vorin (CF) in Patients With Metastatic ColorectalCarcinoma Previously Treated With Oxaliplatin (OXAL) or a Combinationof CPT-11 and OXAL

N0148 Study to Estimate the Benefit of 5-FU-Based Treatment as SurgicalAd-juvant Therapy by Gender, Primary Site and Nodal Stage in Patientswith Dukes' C Colon Cancer Compared to Controls Who Were Not Treated N9741 A Randomized Phase III Trial of Combinations of Oxaliplatin

(OXAL),5-Fluorouracil (5-FU), and Irinotecan (CPT-11) as Initial Treat-ment ofPatients With Advanced Adenocarcinoma of the Colon and Rec-tum

N9841 A Randomized Phase III Equivalence Trial of Irinotecan (CPT-11) Ver-susOxaliplatin (OXAL)/5-Fluorouracil (5-FU)/Leucovorin (CF) in PatientsWith Advanced Colorectal Carcinoma Previously Treated With 5-FU

N9945 A Phase II Trial Evaluating Multiple Metastasectomy Combined With-Hepatic Artery Infusion of Floxuridine (FUDR) and Dexamethasone (DXM)Alternating With Systemic Oxaliplatin (OXAL) and Capecitab-ine (CAPCIT)for Colorectal Carcinoma Metastatic to the Liver

N9946 A Phase II Study of Oxaliplatin (OXAL), 5-Fluorouracil (5-FU), andLeucovorin (CF)in Patients With Metastatic Colorectal Carcino-maPreviously Treated With Irinotecan (CPT-11)

R9811 A Phase III Randomized Study of 5-fluorouracil, Mitomycin-C, andRa-diotherapy Versus 5-fluorouracil, Cisplatin and RaandRa-diotherapy inCarci-noma of the Anal Canal

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Program Status Reports for GASTROINTESTINAL - October 2002

964152 A Phase II Trial of CPT-11 in Patients With Advanced Adenocarcinoma ofthe Stomach or Gastroesophageal Junction Incorporating Pretreat-mentand Posttreatment Biopsies for Evaluation of Tumor Thymidylate-Synthase, MIB-1, Topoisomerase I, and p53

N0041 Phase II Trial of Gemcitabine and Docetaxel in Patients WithMeasurable Unresectable or Metastatic Hepatocellular Carcinoma

N0042 Phase II Trial of Gemcitabine, 5-Fluouracil, and Leucovorin inPatients With Unresectable or Metastatic Biliary Tract Carcinoma(Intrahepatic, Extrahepatic, Ampulla of Vater) and GallbladderCarcinoma

N0043 Phase II Trial of Gemcitabine and ISIS 2503 in Patients With Locally-Advanced or Metastatic Pancreatic Adenocarcinoma

N0044 A Phase II Trial of Preoparative Radiation and Chemotherapy(Pacli-taxel, Carboplatin, and Continuous Infusion 5-FU) in CombinationWith Subcutaneous Amifostine for Locally Advanced Esophageal Cancer N0093 Topoisomerase Inhibitors in Gastric and Glioma Tumors

N9942 A Phase II Study of Gemcitabine, Cisplatin and Radiation Therapy inPa-tients with Locally Advanced Pancreatic Cancer

Translational Studies

MC9944 Colorectal Cancer Screening: Fecal Blood vs. DNA

Other Closed Trials

904652 A Controlled Phase III Evaluation of 5FU Combined with Levamisole andLeucovorin as Surgical Adjuvant Treatment Following Total Gross-Resection of Metastatic Colorectal Cancer

914652 Intergroup - Phase III Study of Radiation Therapy, Levamisole, and5-Fluorouracil vs 5-and5-Fluorouracil and Levamisole in Selected PatientsWith Completely Resected Colon Cancer

914653 A Phase III Evaluation of High-Dose Levamisole Plus 5-Fluorouracil andLeucovorin as Surgical Adjuvant Therapy for High Risk Colon Can-cer

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Program Status Reports for GASTROINTESTINAL - October 2002

924652 Phase II Trial: Evaluation of the Role of Multiple MetastasectomyCom-bined with Systemic and Hepatic Artery Infusion Chemotherapy forCol-orectal Carcinoma Metastatic to the Liver

934652 Evaluation of Tumor Thymidylate Synthase, Ki-67, DCC, and p53 asPrognostic Parameters in Patients With High-Risk Primary Colon Cancer

934653 A Phase III Prospective Randomized Trial ComparingLaparoscopic-Assisted Colectomy Versus Open Colectomy for Colon Cancer 934751 Postoperative Evaluation of 5FU by Bolus Injection VS5FU by

Pro-longedVenous Infusion Prior to and Following Combined Prolonged VenousInfusion Plus Pelvic XRT Vs. Bolus 5FU Plus Leucovorin Plus LevamisolePrior to and Following Combined PelvicXRT in Patients With RectalCancer, Phase III

950452 Apoptosis, Cell Proliferation, and DNA Ploidy in Patients with

Dukes'B2 and C Stage Adenocarcinoma: An Ancillary Study to NCCT-GChemotherapy Protocols for Colon Cancer

954651 A Phase II Trial of a Seven Day Regimen of Oral 776C85 and Oral5-Flourouracil (5-FU) in Untreated Patients with Unresectable orMeta-static Colorectal Cancer

964252 Phase II Study of CPT-11 in Patients With Advanced Gallbladder or BileDuct Tumors

964352 Phase I Study of Gemcitabine, Cisplatin and Radiation Therapy inPa-tients with Locally Advanced Pancreatic and Gastric Cancer

984351 A Phase I (Limited)/Phase II Study of Oxaliplatin (OXAL) andGemcit-abine (GEMZAR) in Patients with Metastatic Pancreatic Carcinoma 984654 The Clinical and Pathologic Significance of Allelic Imbalance of 8p

inPatients With Colorectal Cancer

C89803 Phase III Intergroup Trial of Irinotecan (CPT-11) (NSC #616348) Plus-Fluorouracil/Leucovorin (5-FU/LV) Versus Plus-Fluorouracil/Leucovorin AloneAfter Curative Resection for Patients with Stage III Colon Cancer C9781 A Prospective Randomized Phase III Trial Comparing Trimodality

Ther-apy(Cisplatin, 5-FU, Radiotherapy, and Surgery) to Surgery Alone ForEsophageal Cancer.

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Program Status Reports for GASTROINTESTINAL - October 2002

JCO10 A Phase III Study of Immediate versus Delayed Chemotherapy forAs-ymptomatic Advanced Colorectal Cancer

N004A Study to Estimate the Toxicity, Dose Intensity, and Benefit of5-FU-Based Treatment by Age Group in Patients with Advanced ColonCancer N0144 Profile of Long-Term Survivors on NCCTG Advanced Colorectal

Can-cerTreatment Trials

N9742 An Analysis of the Incidence by Grade of Acute GastrointestinalToxic-ity in Patients Receiving Adjuvant Continuous InfusionChemotherapy and Radiotherapy for High-Risk Rectal Carcinoma

N9743 Study to Estimate the Benefit of 5-FU-Based Treatment asSurgicalAdju-vant Therapy by Age Group in Patients With ResectableHigh-Risk Colon cancer Compared to Controls Who Were Not Treated

N9941 A Phase II Study of Taxotere and Irinotecan (CPT-11) in Patients with-Advanced Adenocarcinoma of the Lower Esophagus, Esophagogastric-Junction, and Gastric Cardia

N9949 Women Experience Greater Toxicity With 5FU-Based Chemotherapy (CTX)for Colorectal Cancer (CC): A North Central Cancer Treatment Group(NCCTG) Meta-Analysis

S9415 A Phase III Randomized Trial of 5-FU/Leucovorin/Levamisole Versus 5-FUContinuous Infusion/Levamisole as Adjuvant Therapy for High-RiskResectable Colon Cancer

Protocol Concepts

N004B Phase III Randomized, Double-Blind, Placebo-Controlled Study ofRO-FECOXIB (VIOXX) in Colorectal Cancer Patients Following Potential-lyCurative Therapy

N004C Evaluation of the Predictive Ability of Defective Mismatch

Repair(MMR) (Measured either by Microsatellite Instability (MSI-H) orAbsence of Protein Expression for hMLH1 and hMSH2) for Efficacy of5-FU Based Adjuvant Therapy for Stage II and III Colon Cancer N0147 Phase III Trial of Irinotecan (CPT-11) Plus

5-Fluorouracil(5-FU)/Leuco-vorin (CF) Versus Oxaliplatin (OXAL) Plus5-Fluoracil/Leuco5-Fluorouracil(5-FU)/Leuco-vorin After Curative Resection for Patients withStage III Colon Cancer

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Program Status Reports for GASTROINTESTINAL - October 2002

N0149 A Phase II Study of Oxaliplatin and Capecitabine in Patients withMeta-static Adenocarcinoma of the Esophagus, Gastroesophageal Junc-tion,and Gastric Cardia

N014A A Phase II Study of Oxaliplatin, 5-Fluorouracil, Leucovorin, and

C225for Patients With Unresectable Hepatic Metastases from Metastati-cAdenocarcinoma of the Colon or Rectum

N0242 A Phase II Study of Docetaxel and Capecitabine in Patients withMeasur-able Metastatic Adenocarcinoma of the Stomach andGastroesophageal Junction

N9943 Phase I/II Trial of Gemcitabine and MTA in Patients with Meaasurable-Unresectable or Metastatic Biliary Tract Carcinoma (Intrahepatic,Extra-hepatic, Ampulla of Vater) and Gallbladder Carcinoma

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NCCTG Status Report for Study 974651 - October 2002

974651 - Page 1 of 3

A Phase II Study of Patients With Unresectable Hepatic Metastases from

Met-astatic Adenocarcinoma of the Colon or Rectum

Purpose of Study:

1) To evaluate the resectability rate of this patient population group after treat-ment with OXAL, 5-FU and CF.

2) To assess the response rate, toxicity and overall survival of this same group.

Study Chairs: Steven R. Alberts M.D. William C. Sternfeld M.D. William L. Horvath M.D.

QC Specialist: Deborah J. Papenfus

Statistician: Michelle R. Mahoney M.S. Nurse Resource: Tammy Fischer R.N.

Status: 03/26/1999 08/31/2001

Activated Perm. Closed

Projected Number of Patients: 44

Excluded: 1 Final Accrual: 44

Stratification None

Schema: Register

OXAL + 5FU + CF

Treating Schedule:

Arm Agent Dose Route Days Freq

OXAL 85 mg/m2 IV over 2 hrs 1 2 wks

CF 200 mg/m2 IV over 2 hrs 1, 2 2 wks

5FU 400 mg/m2 IV bolus after CF 1, 2* 2 wks 5FU 600 mg/m2 Continuous IV infusion

after bolus 5FU

1, 2 2 wks

*Patients receive bimonthly high-dose CF with 5FU bolus and continuous infusion for 2 consecutive days. CF is given at 200 mg/m2/day as a 2-hr infusion followed by IV bolus 5FU at 400 mg/m2/day and 22-hr infusion 5FU 600 mg/m2/day, all repeated for 2 consecutive days.

Study Design: The primary endpoint is the surgical complete response (surgical CR) rate.

Thirty-nine evaluable patients will be enrolled with the provision that if 0 or more than 2 patients in the first 28 evaluable demonstrate a surgical CR, we will stop accrual to either report a poor result or a promising result, respectively. If 1 in 28 evaluable patients demonstrate a surgical CR, we will accrue an additional 11 patients. If 1 in 39 show surgical CR, we will conclude inactivity of this treatment in this population. If 2 or more in 39 patients demonstrate a surgical CR, we will consider the study of this treatment in larger studies.

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NCCTG Status Report for Study 974651 - October 2002

974651 - Page 2 of 3

Accrual: This study has completed accruing patients. See NCCTG 2001 book for accrual

information.

Patient Characteristics: The distribution of patient characteristics at study entry is located in

the Patient Characteristics Table.

Available Information: One patient is ineligible due to extrahepatic metastases. All other

patients are eligible.

Adverse Events: Toxicity data is available for 42 eligible patients. Grade IV toxicity has been

minimal (diarrhea-2 pts, arrythmia-2 pts, vomiting-1 pt, hypokalemia-1 pt). See Adverse Event Table for further details.

Study Status: This study is closed to accrual and data is maturing. An abstract accepted for

poster discussion at the ASCO 2001 meetings appeared in the 2001 NCCTG meeting book. A replacement study is currently in development and anticipated to open in late 2002 (i.e., N014A).

Baseline Characteristics Table:

Characteristics Arm A Gender f 20 m 24 Liver Metastases MULTIPLE 21 ILL-LOCATED 3 LARGE 3 COMBINATION 15 Race Black 1 Native Americian 1 White 42

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NCCTG Status Report for Study 974651 - October 2002

974651 - Page 3 of 3

Grade 4/5 and Most Frequent Adverse Event Table: Arm A Evaluable Patients: 42

Body System Adverse Event A R M

Maximum Severity Per Patient Grade 1/2 Grade 3 Grade 4 Grade 5

N % N % N % N % Hematology NEUTROPENIA A ₁₀ ₂₄ ₄ ₁₀ ₀ ₀ ₀ ₀ LEUKOPENIA A ₂₄ ₅₇ ₁₁ ₂₆ ₀ ₀ ₀ ₀ ANEMIA A ₁₈ ₄₃ ₂ ₅ ₀ ₀ ₀ ₀ THROMBOCYTOPENIA A ₂₇ ₆₄ ₁ ₂ ₀ ₀ ₀ ₀ Cardiovascular ARRHYTHMIA-SVT A ₀ ₀ ₂ ₅ ₁ ₂ ₀ ₀ Constitutional Symptoms FATIGUE A ₂₂ ₅₂ ₀ ₀ ₀ ₀ ₀ ₀ Dermatology/Skin ALOPECIA A ₁₇ ₄₀ ₀ ₀ ₀ ₀ ₀ ₀ RASH A ₁₁ ₂₆ ₀ ₀ ₀ ₀ ₀ ₀ Gastrointestinal ANOREXIA A ₁₂ ₂₉ ₃ ₇ ₀ ₀ ₀ ₀ NAUSEA A ₂₆ ₆₂ ₅ ₁₂ ₀ ₀ ₀ ₀ STOMATITIS A ₁₉ ₄₅ ₁ ₂ ₀ ₀ ₀ ₀ CONSTIPATION A ₆ ₁₄ ₁ ₂ ₀ ₀ ₀ ₀ VOMITING A ₁₈ ₄₃ ₃ ₇ ₁ ₂ ₀ ₀ DIARRHEA-NO COLOSTOM A ₁₈ ₄₃ ₅ ₁₂ ₂ ₅ ₀ ₀

Hepatic SGOT (AST) A ₁₄ ₃₃ ₀ ₀ ₀ ₀ ₀ ₀

ALK PHOS A ₁₆ ₃₈ ₀ ₀ ₀ ₀ ₀ ₀ BILIRUBIN A ₅ ₁₂ ₀ ₀ ₀ ₀ ₀ ₀ Metabolic/Laboratory HYPOKALEMIA A ₁ ₂ ₁ ₂ ₁ ₂ ₀ ₀ Neurology NEURO A ₃₇ ₈₈ ₃ ₇ ₀ ₀ ₀ ₀ Pain PAIN-ABDOMINAL A ₈ ₁₉ ₂ ₅ ₀ ₀ ₀ ₀ Renal/Genitourinary CREATININE A ₁₁ ₂₆ ₀ ₀ ₀ ₀ ₀ ₀ Maximum Grade Adverse Event A ₉ ₂₁ ₂₇ ₆₄ ₅ ₁₂ ₀ ₀

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NCCTG Status Report for Study C9581 - October 2002

C9581 - Page 1 of 2

Phase III Randomized Study of Adjuvant Immunotherapy With Monoclonal

Antibody 17-1A Versus No Adjuvant Therapy Following Resection for Stage II

(Modified Astler-Coller B2) Adenocarcinoma of the Colon

1) To determine whether adj MoAb 17-1A will improve overall/disease-free survival, and increase disease-free intervals in study patients.

2) To evaluate prognostic markers in order to correlate survival and recurrence for study patients.

Study Chairs: Richard M. Goldberg M.D. Rex B. Mowat M.D. Fredric H. Itzkowitz D.O.

QC Specialist: Carol A. Leonard

Statistician: Nurse Resource:

Status: 11/26/1997 05/31/2002

Activated Perm. Closed

Excluded: None Final Accrual: 263

Stratification Histology-degree of differentiation Histology-vascular or lymphatic inva-sion

Factors: Preoperative serum CEA

Schema: Randomize A) MoAb-17 B) Observation

A MOAB 17-1A 500 MG INFUSION OVER 2 HRS 1 CYCLE 1 ONLY A MOAB 17-1A 100 MG INFUSION OVER 2 HRS 1 EVERY 28 DAYS CYCLES 2-5

Study Design: The goal of this CALGB-coordinated study is to determine whether adjuvant

immunotherapy with infusion of MoAb 17-1A improves the overall and disease-free survival of patients with Stage B2 colon cancer compared to an observation group receiving the current rec-ommended standard of care, i.e., no adjuvant therapy after surgical resection. In addition, this study will evaluate a panel of prognostic markers, in order to correlate these measures with sur-vival and recurrence after adjuvant therapy in patients who have undergone resection of a Stage II (pT3N0 or pT4bN0) colon cancer.

Accrual: This study closed 5/31/2002. As of March 31, 2002, 1656 patients, had been accrued,

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NCCTG Status Report for Study C9581 - October 2002

C9581 - Page 2 of 2

Adverse Events: With toxicity information available on 836 patients, there have been 69

instances of Grade 3 toxicities and 15 instances of Grade 4 toxicity. The Grade 4 toxicities include diarrhea (6), dyspnea (1), vomiting (1), lymphocytopenia (1), dysrhythemias (1), GI other (1), and allergy (3).

Study Status: The study is closed to accrual.

Accrual Table: Randomizing Membership Total Entered Past 6 Months Past 12 Months Ann Arbor 1 0 0 Bismarck 2 0 0 Carle 18 4 6 Cedar Rapids 27 1 3 Des Moines 24 1 4 Duluth 16 1 3 Fargo 12 1 2 Grand Forks 1 0 0 Mayo 21 2 3 Mo Valley 28 3 7 Rapid City 4 0 0 Saskatchewan 39 2 6 Scottsdale 14 2 2 Sioux City 3 0 0 St. Cloud 12 0 3 Toledo 41 2 3

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NCCTG Status Report for Study N0048 - October 2002

N0048 - Page 1 of 4

Phase II Studies of Irinotecan (CPT-11) or 5-Fluorouracil (5-FU)/Leucovorin

(CF) in Patients With Metastatic Colorectal Carcinoma Previously Treated

With Oxaliplatin (OXAL) or a Combination of CPT-11 and OXAL

1) To evaluate tumor response rate to CPT-11, and 5FU/CF in this patient pop-ulation.

2) To evaluate time to tumor progression, time to treatment failure, treatment toxicity, and overall survival.

3) Assess the quality-of-life during chemotherapy.

Study Chairs: Henry C. Pitot IV M.D. Martin Wiesenfeld M.D.

Statistician: Michelle R. Mahoney M.S. Nurse Resource: Tammy Fischer R.N.

Status: 04/13/2001 Activated Projected Number of Patients: 80

Excluded: None Final Accrual: NA

Schema: Register

For patients with prior OXAL A) CPT-11

For patients with prior CPT-11 + OXAL B) CF + 5FU

A CPT-11 350 mg/m2 IV infusion of 500 ml D5W over 90 min 1 3 wks B CF 200 mg/m2 IV over 2 hrs in 250 ml D5W 1,2 2 wks

5FU 400 mg/m2 IV bolus followed by IV 1,2 2 wks 5FU 600 mg/m2 Continuous IV infusion

after bolus 5FU

1,2 2 wks

Study Design: This study evaluates two treatments (i.e., Arms) in a concurrent manner. The

primary endpoint of this trial is confirmed tumor response. The same statistical design will be independently applied to evaluate each arm with respect to the primary endpoint. We will enroll 20 patients onto this study. If 1 or fewer confirmed responses are observed in 20 evaluable patients, we will terminate the study. Otherwise, we will expand accrual to a total of 40 patients. Five confirmed responses in all 40 evaluable patients is considered sufficient evidence of prom-ising activity in this patient population.

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NCCTG Status Report for Study N0048 - October 2002

N0048 - Page 2 of 4

Accrual: This study has had an accrual of 10 patients thus far. Four patients have been accrued

in the last 6 months. See Accrual Table.

Available Information: One patient has been registered to date. Eight patients are in active

treatment and one has begun event monitoring.

Adverse Events: Toxicity data is available for 6 patients. See Adverse Event Table for details.

Study Status: This study is currently open. Patients registered to N9741 and receiving one of

the OXAL-based regimens, may be eligible for this study after progression.

Accrual Table for OXAL BASED CHEMO:

Randomizing Membership Total Entered Past 6 Months Past 12 Months Carle 1 1 1 Cedar Rapids 1 1 1 Jacksonville 1 0 1 Mayo 3 2 3 Mo Valley 2 0 2 Peoria 1 0 0 Saskatchewan 1 0 1

Total Membership Accrual 10 4 9

Accrual Table for COMBINED CPT-11 AND OXAL CHEMO:

Randomizing Membership Total Entered Past 6 Months Past 12 Months Cedar Rapids 1 0 1 Des Moines 1 1 1 Metro 1 1 1 Saskatchewan 2 0 2

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NCCTG Status Report for Study N0048 - October 2002

N0048 - Page 3 of 4 GI NCCTG GI Committee Characteristics Arm A Arm B Gender f 2 0 m 8 0

Prior Treatment Received

COMBINED CPT-11 AND OXAL CHEMO 0 0

OXAL BASED CHEMO 10 0

Race

Other 1 0

White 9 0

Baseline Characteristics Table for COMBINED CPT-11 AND OXAL CHEMO:

Characteristics Arm A Arm B Gender f 0 2 m 0 3

Prior Treatment Received

COMBINED CPT-11 AND OXAL CHEMO 0 5

OXAL BASED CHEMO 0 0

Race

Other 0 0

White 0 5

Grade 4/5 and Most Frequent Adverse Event Table for OXAL BASED CHEMO: Arm A Evaluable Patients: 6

N % N % N % N % Hematology NEUTROPENIA A ₁ ₁₇ ₁ ₁₇ ₄ ₆₇ ₀ ₀ LEUKOPENIA A ₁ ₁₇ ₄ ₆₇ ₁ ₁₇ ₀ ₀ ANEMIA A ₃ ₅₀ ₀ ₀ ₀ ₀ ₀ ₀ LYMPHOPENIA A ₀ ₀ ₁ ₁₇ ₀ ₀ ₀ ₀ THROMBOCYTOPENIA A ₅ ₈₃ ₀ ₀ ₀ ₀ ₀ ₀ Allergy/Immunology AUTOIMMUNE DISORDER A ₁ ₁₇ ₀ ₀ ₀ ₀ ₀ ₀ Constitutional Symptoms FATIGUE A ₁ ₁₇ ₀ ₀ ₀ ₀ ₀ ₀ Dermatology/Skin ALOPECIA A ₆ ₁₀₀ ₀ ₀ ₀ ₀ ₀ ₀ Gastrointestinal ANOREXIA A ₁ ₁₇ ₀ ₀ ₀ ₀ ₀ ₀

NAUSEA A ₅ ₈₃ ₁ ₁₇ ₀ ₀ ₀ ₀

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NCCTG Status Report for Study N0048 - October 2002

N0048 - Page 4 of 4 GI NCCTG GI Committee VOMITING A ₂ ₃₃ ₀ ₀ ₀ ₀ ₀ ₀ DIARRHEA-NO COLOSTOM A ₄ ₆₇ ₀ ₀ ₁ ₁₇ ₀ ₀ DIARRHEA-COLOSTOM A ₁ ₁₇ ₀ ₀ ₀ ₀ ₀ ₀

Hepatic SGOT (AST) A ₂ ₃₃ ₀ ₀ ₀ ₀ ₀ ₀

ALK PHOS A ₃ ₅₀ ₀ ₀ ₀ ₀ ₀ ₀

HYPOALBUMINEMIA A ₁ ₁₇ ₀ ₀ ₀ ₀ ₀ ₀ Metabolic/Laboratory HYPOKALEMIA A ₁ ₁₇ ₀ ₀ ₀ ₀ ₀ ₀ HYPOPHOSPHATEMIA A ₁ ₁₇ ₀ ₀ ₀ ₀ ₀ ₀ METABOLIC/LAB A ₀ ₀ ₁ ₁₇ ₀ ₀ ₀ ₀ Neurology LOW CONSCIOUSNESS A ₁ ₁₇ ₀ ₀ ₀ ₀ ₀ ₀

DEPRESSION A ₀ ₀ ₁ ₁₇ ₀ ₀ ₀ ₀

CONFUSION A ₀ ₀ ₀ ₀ ₁ ₁₇ ₀ ₀

ANXIETY A ₀ ₀ ₁ ₁₇ ₀ ₀ ₀ ₀

PERSONALITY CHANGE A ₀ ₀ ₁ ₁₇ ₀ ₀ ₀ ₀ Maximum Grade Adverse Event A ₁ ₁₇ ₁ ₁₇ ₄ ₆₇ ₀ ₀

Grade 4/5 and Most Frequent Adverse Event Table for COMBINED CPT-11 AND OXAL CHEMO:

Arm B Evaluable Patients: 2

N % N % N % N %

Hematology NEUTROPENIA B ₂ ₁₀₀ ₀ ₀ ₀ ₀ ₀ ₀

LEUKOPENIA B ₁ ₅₀ ₀ ₀ ₀ ₀ ₀ ₀

ANEMIA B ₁ ₅₀ ₀ ₀ ₀ ₀ ₀ ₀

LYMPHOPENIA B ₁ ₅₀ ₀ ₀ ₀ ₀ ₀ ₀ Allergy/Immunology RHINITIS ALLERGIC B ₁ ₅₀ ₀ ₀ ₀ ₀ ₀ ₀ Constitutional Symptoms FATIGUE B ₁ ₅₀ ₀ ₀ ₀ ₀ ₀ ₀

RIGORS B ₁ ₅₀ ₀ ₀ ₀ ₀ ₀ ₀ WEIGHT GAIN B ₁ ₅₀ ₀ ₀ ₀ ₀ ₀ ₀ Dermatology/Skin RASH B ₁ ₅₀ ₀ ₀ ₀ ₀ ₀ ₀ Gastrointestinal ANOREXIA B ₁ ₅₀ ₀ ₀ ₀ ₀ ₀ ₀ DIARRHEA-NO COLOSTOM B ₂ ₁₀₀ ₀ ₀ ₀ ₀ ₀ ₀ Metabolic/Laboratory METABOLIC/LAB B ₂ ₁₀₀ ₀ ₀ ₀ ₀ ₀ ₀ Ocular/Visual TEARING B ₁ ₅₀ ₀ ₀ ₀ ₀ ₀ ₀

Maximum Grade Adverse Event B ₂ ₁₀₀ ₀ ₀ ₀ ₀ ₀ ₀ Body System Adverse Event A R M

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NCCTG Status Report for Study N0148 - October 2002

N0148 - Page 1 of 1

Study to Estimate the Benefit of 5-FU-Based Treatment as Surgical Adjuvant

Therapy by Gender, Primary Site and Nodal Stage in Patients with Dukes' C

Colon Cancer Compared to Controls Who Were Not Treated

1) To estimate via pooled-analysis the benefit of 5FU-based treatment as surgi-cal adjuvant therapy by gender, primary site & nodal stage groups in

patients with resectable high-risk colon cancer compared to controls who were not treated.

Study Chairs: Steven R. Alberts M.D. Stephan D. Thome M.D.

QC Specialist:

Statistician: Daniel J. Sargent Ph.D. Nurse Resource:

Status: 12/07/2001 Activated Projected Number of Patients: 3351

Factors:

Schema: Not Applicable

Not applicable

Study Design: This retrospective trial is using data previously collected from multiple

random-ized phase III trials throughout the U.S. and Europe. The goal is to determine if the benefit received from 5-FU based treatment varies by patient gender, primary site, nodal stage, and tumor grade.

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NCCTG Status Report for Study N9741 - October 2002

N9741 - Page 1 of 15

A Randomized Phase III Trial of Combinations of Oxaliplatin (OXAL),

5-Flu-orouracil (5-FU), and Irinotecan (CPT-11) as Initial Treatment of Patients

With Advanced Adenocarcinoma of the Colon and Rectum

Purpose of 1) To evaluate time to progression for the study population.

Study: 2) To evaluate toxicity, response rate, time to treatment failure and survival. 3) To compare quality of life parameters.

Study Chairs: Richard M. Goldberg M.D. Roscoe F. Morton M.D.

Statistician: Daniel J. Sargent Ph.D. Nurse Resource: Tammy Fischer R.N.

Status: 10/27/1998 03/24/2000 04/28/2000 04/25/2001 06/29/2001 07/19/2002 Activated Temp. Closed Reopened Temp. Closed Reopened Perm. Closed

Excluded: 32 Final Accrual: 1752

Stratification Age Dominant Disease Status

Factors: Membership Prior Adjuvant Chemotherapy

Prior Immunotherapy ECOG PS

Schema: Randomize

A) Saltz Regimen

B) Mayo CPT-11 Regimen (closed) C) Wilke Regimen (closed)

D) Standard 5FU/CF Regimen (closed) E) OXAL bolus Regimen (closed) F) OXAL Infusion Regimen G) OXAL + CPT-11 (closed)

A CPT-11 100 mg/m2 IV infusion 500 ML D5W over 90 min

1 Every 42 days (Rx Wks 1-4 Rest Wks 5 & 6)

A CF 20 mg/m2 IV infusion 15 min 1-after CPT-11 Every 42 days (Rx Wks 1-4 Rest Wks 5 & 6)

A 5FU 400 mg/m2 IV bolus 1-after CF Every 42 days (Rx Wks 1-4 Rest Wks 5 & 6)

F OXAL 85 mg/m2 IV infusion 500 ML D5W over 120 min

1 Every 14 days (Rx Wk 1 Rest Wk 2)

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NCCTG Status Report for Study N9741 - October 2002

N9741 - Page 2 of 15

F CF 200 mg/m2 120 min infusion 1, 2 Every 14 days (Rx Wk 1 Rest Wk 2)

F 5FU 400 mg/m2 then 600 mg/m2

IV BOLUS then IV infu-sion thru ambulatory

pump over 22 hrs

1, 2 after CF Every 14 days (Rx Wk 1 Rest Wk 2)

G OXAL 85 mg/m2 IV infusion in 500 ML D5W over 120 min

1 Every 21 days (Rx Wk 1 Rest Wks 2 & 3) G CPT-11 200 mg/m2 30 min infusion 1 Every 21 days (Rx Wk 1 Rest

Wks 2 & 3)

Study Design: Two drugs are currently FDA-approved in the U.S. for treatment of first-line

advanced colon cancer. The combination of CPT-11, 5-FU, and CF is standard therapy in the U.S. for patients with advanced disease. Oxaliplatin (OXAL) is a cisplatinum analogue with activity in colorectal cancer that is now approved for second-line treatment in the U.S. A com-parison of regimens which combine 5-FU + OXAL + CF and OXAL + CPT-11 is of great inter-est to advance the therapy of advanced colorectal cancer. This trial's results will also provide data that can be used to help develop future adjuvant trials.

The primary objective of this trial is to compare the time-to-progression in patients with locally advanced or metastatic colorectal cancer (previously untreated for advanced disease) who receive OXAL + 5-FU + CF or CPT-11 + OXAL to those receiving standard CPT-11 + 5-FU + CF. This is a 3-arm randomized trial with equal allocation to each arm. The total sample size required is 1705 patients.

Accrual: Accrual to the study closed on July 19, 2002 with a total accrual of 1752 patients.

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NCCTG Status Report for Study N9741 - October 2002

N9741 - Page 3 of 15

Adverse Events: Toxicity information is available for 1251 patients, 71% of the enrolled 1752

patients. In late fall 1999, multiple grade 5 toxicities were observed on arms B and E, specifi-cally, on each of these two arms 3 patients died from at least possibly treatment related causes. These two arms were subsequently removed from the study, in part due to this toxicity. In the spring of 2001, what had been a trend toward an increased early fatality rate on arm A became more pronounced. This finding led to a suspension of accrual pending a dose modification on arm A. Subsequent to the study closing, the toxicity on arm A was extensively investigated and reported. The experience on this trial, and a related CALGB trial, were described in a letter to the editor of the New England Journal of Medicine dated July 12, 2001. Subsequently, an exter-nal, independent panel reviewed each death within 60 days of study entry on this and the related CALGB study. The report of this committee was published in the Journal of Clinical Oncology (19(18):3801-3807, 2001). Alopecia, anorexia, nausea, fatigue, stomatitis, vomiting and diar-rhea are the most common non hematologic toxicities. See the attached toxicity tables for com-plete toxicity information. Specifically, the adverse event profile of the reduced doses of arm A has been very acceptable.

Study Status: Accrual to this study closed in July. All patients enrolled on the trial have the

option of receiving treatment on arm F. In addition, after progression on arms F or G, patients may be eligible for trial NCCTG N0048. Intense efforts are now underway to obtain, enter, Q/C, and analyze the data from this trial in order to allow a presentation to the FDA in support of a first-line indication for Oxaliplatin.

Additional Information: An updated abstract presented at the 2002 ASCO meetings is

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NCCTG Status Report for Study N9741 - October 2002

N9741 - Page 4 of 15 GI NCCTG GI Committee Accrual Table: Randomizing Membership Total Entered Past 6 Months Past 12 Months Ann Arbor 26 1 9 Bismarck 8 0 1 Carle 26 4 5 Cedar Rapids 34 2 6 Des Moines 14 5 11 Duluth 45 11 15 Fargo 9 4 5 Geisinger 15 3 6 Grand Forks 12 1 3 Jacksonville 4 4 4 Mayo 30 3 15 Metro 31 7 8 Mo Valley 41 6 11 Ochsner 10 0 1 Peoria 40 7 15 Rapid City 9 2 2 Saskatchewan 51 2 15 Scottsdale 25 1 12 Sioux City 5 0 0 Sioux Falls 11 0 3 St. Cloud 7 0 1 Toledo 27 3 4 Wichita 35 6 12

Randomizing Group Total Entered Past 6 Months Past 12 Months NCCTG 515 72 164 ECOG 298 79 162 SWOG 266 99 150 CALGB 443 100 153 NCIC CTG 170 44 65 EPP 60 2 10

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NCCTG Status Report for Study N9741 - October 2002

N9741 - Page 5 of 15

Baseline Characteristics Table:

Characteristics Arm A Arm B Arm C Arm D Arm E Arm F Arm G Age <65 265 39 9 37 28 419 235 >=65 162 22 5 24 19 274 145 Disease Status MEASURABLE 373 46 9 48 46 590 328 EVALUABLE 54 15 5 13 1 103 52 ECOG PS 0-1 408 56 14 58 44 661 361 2 19 5 0 3 3 32 19 Gender f 153 28 6 23 20 282 153 m 277 33 8 38 27 414 230

Prior Adjuvant Chemotherapy

Yes 60 7 2 8 8 109 55 No 367 54 12 53 39 584 325 Race Asian 1 0 0 0 1 15 3 Black 39 4 1 3 4 50 27 Hispanic 13 0 0 2 1 28 14 Native Americian 2 0 0 1 0 1 2

Native Hawaiian or Other Pacific Islande 1 0 0 1 0 3 1

Other 2 1 0 0 0 4 1

Unknown 0 0 0 0 0 5 0

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NCCTG Status Report for Study N9741 - October 2002

N9741 - Page 6 of 15

Adverse Event Table:

Arm A Evaluable Patients: 355 Arm B Evaluable Patients: 55 Arm C Evaluable Patients: 14 Arm D Evaluable Patients: 60 Arm E Evaluable Patients: 45 Arm F Evaluable Patients: 386 Arm G Evaluable Patients: 336

N % N % N % N % Hematology NEUTROPENIA A ₁₂₄ ₃₅ ₇₈ ₂₂ ₄₇ ₁₃ ₀ ₀ B ₁₂ ₂₂ ₂ ₄ ₆ ₁₁ ₀ ₀ C ₄ ₂₉ ₀ ₀ ₁ ₇ ₀ ₀ D ₅ ₈ ₁ ₂ ₁₅ ₂₅ ₀ ₀ E ₁₁ ₂₄ ₅ ₁₁ ₃ ₇ ₀ ₀ F ₁₀₉ ₂₈ ₁₁₂ ₂₉ ₅₅ ₁₄ ₀ ₀ G ₁₁₉ ₃₅ ₆₄ ₁₉ ₅₇ ₁₇ ₀ ₀ LEUKOPENIA A ₁₅₆ ₄₄ ₅₉ ₁₇ ₁₈ ₅ ₀ ₀ B ₉ ₁₆ ₈ ₁₅ ₅ ₉ ₀ ₀ C ₄ ₂₉ ₃ ₂₁ ₀ ₀ ₀ ₀ D ₂₄ ₄₀ ₉ ₁₅ ₂ ₃ ₀ ₀ E ₁₉ ₄₂ ₂ ₄ ₂ ₄ ₀ ₀ F ₁₇₉ ₄₆ ₆₃ ₁₆ ₃ ₁ ₀ ₀ G ₁₂₁ ₃₆ ₅₉ ₁₈ ₂₆ ₈ ₀ ₀ ANEMIA A ₉₃ ₂₆ ₁₁ ₃ ₂ ₁ ₀ ₀ B ₂₀ ₃₆ ₁ ₂ ₀ ₀ ₀ ₀ C ₂ ₁₄ ₀ ₀ ₀ ₀ ₀ ₀ D ₈ ₁₃ ₀ ₀ ₀ ₀ ₀ ₀ E ₁₂ ₂₇ ₀ ₀ ₀ ₀ ₀ ₀ F ₉₇ ₂₅ ₉ ₂ ₁ ₀ ₀ ₀ G ₇₅ ₂₂ ₁₁ ₃ ₁ ₀ ₀ ₀ THROMBOCYTOPENIA A ₂₆ ₇ ₉ ₃ ₀ ₀ ₀ ₀ B ₃ ₅ ₁ ₂ ₀ ₀ ₀ ₀ C ₁ ₇ ₀ ₀ ₀ ₀ ₀ ₀ D ₁ ₂ ₀ ₀ ₀ ₀ ₀ ₀ E ₉ ₂₀ ₃ ₇ ₁ ₂ ₀ ₀ F ₁₅₈ ₄₁ ₁₀ ₃ ₂ ₁ ₀ ₀ G ₆₈ ₂₀ ₁₃ ₄ ₁ ₀ ₀ ₀ Auditory/Hearing INNER EAR A ₁ ₀ ₀ ₀ ₀ ₀ ₀ ₀ B ₀ ₀ ₀ ₀ ₀ ₀ ₀ ₀ C ₀ ₀ ₀ ₀ ₀ ₀ ₀ ₀

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NCCTG Status Report for Study N9741 - October 2002

N9741 - Page 7 of 15 GI NCCTG GI Committee D ₀ ₀ ₀ ₀ ₀ ₀ ₀ ₀ E ₁ ₂ ₀ ₀ ₀ ₀ ₀ ₀ F ₄ ₁ ₀ ₀ ₁ ₀ ₀ ₀ G ₃ ₁ ₁ ₀ ₀ ₀ ₀ ₀ Cardiovascular HYPOTENSION A ₇ ₂ ₆ ₂ ₂ ₁ ₁ ₀ B ₃ ₅ ₀ ₀ ₀ ₀ ₀ ₀ C ₀ ₀ ₀ ₀ ₀ ₀ ₀ ₀ D ₁ ₂ ₁ ₂ ₀ ₀ ₀ ₀ E ₂ ₄ ₁ ₂ ₀ ₀ ₀ ₀ F ₃ ₁ ₈ ₂ ₀ ₀ ₀ ₀ G ₄ ₁ ₆ ₂ ₁ ₀ ₀ ₀ ISCHEMIA/INFARCTION A ₀ ₀ ₁ ₀ ₁ ₀ ₁ ₀ B ₀ ₀ ₀ ₀ ₀ ₀ ₀ ₀ C ₀ ₀ ₀ ₀ ₀ ₀ ₀ ₀ D ₀ ₀ ₀ ₀ ₁ ₂ ₀ ₀ E ₀ ₀ ₀ ₀ ₀ ₀ ₀ ₀ F ₀ ₀ ₀ ₀ ₂ ₁ ₀ ₀ G ₀ ₀ ₀ ₀ ₀ ₀ ₀ ₀ THROMBOSIS A ₀ ₀ ₁₄ ₄ ₃ ₁ ₁ ₀ B ₀ ₀ ₂ ₄ ₀ ₀ ₀ ₀ C ₀ ₀ ₂ ₁₄ ₀ ₀ ₀ ₀ D ₀ ₀ ₂ ₃ ₀ ₀ ₁ ₂ E ₀ ₀ ₁ ₂ ₁ ₂ ₁ ₂ F ₀ ₀ ₂₃ ₆ ₁ ₀ ₁ ₀ G ₀ ₀ ₅ ₁ ₂ ₁ ₀ ₀ EDEMA A ₃₅ ₁₀ ₁ ₀ ₁ ₀ ₀ ₀ B ₆ ₁₁ ₁ ₂ ₀ ₀ ₀ ₀ C ₂ ₁₄ ₀ ₀ ₀ ₀ ₀ ₀ D ₅ ₈ ₀ ₀ ₀ ₀ ₀ ₀ E ₅ ₁₁ ₀ ₀ ₁ ₂ ₀ ₀ F ₄₃ ₁₁ ₀ ₀ ₀ ₀ ₀ ₀ G ₃₂ ₁₀ ₁ ₀ ₀ ₀ ₀ ₀ Constitutional Symptoms FATIGUE A ₁₇₂ ₄₈ ₃₂ ₉ ₆ ₂ ₀ ₀ B ₂₅ ₄₅ ₅ ₉ ₀ ₀ ₀ ₀ C ₁₀ ₇₁ ₀ ₀ ₀ ₀ ₀ ₀ D ₂₄ ₄₀ ₂ ₃ ₀ ₀ ₀ ₀ E ₂₉ ₆₄ ₁ ₂ ₂ ₄ ₁ ₂ F ₂₂₉ ₅₉ ₁₈ ₅ ₁ ₀ ₀ ₀ G ₁₆₅ ₄₉ ₄₅ ₁₃ ₃ ₁ ₀ ₀ Body System Adverse Event A R M

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NCCTG Status Report for Study N9741 - October 2002

N9741 - Page 8 of 15 GI NCCTG GI Committee FEVER-NO ANC A ₃₁ ₉ ₀ ₀ ₀ ₀ ₀ ₀ B ₈ ₁₅ ₀ ₀ ₀ ₀ ₀ ₀ C ₄ ₂₉ ₀ ₀ ₀ ₀ ₀ ₀ D ₃ ₅ ₀ ₀ ₀ ₀ ₀ ₀ E ₉ ₂₀ ₁ ₂ ₀ ₀ ₀ ₀ F ₄₇ ₁₂ ₂ ₁ ₀ ₀ ₀ ₀ G ₂₃ ₇ ₀ ₀ ₀ ₀ ₀ ₀ WEIGHT LOSS A ₃₃ ₉ ₅ ₁ ₀ ₀ ₀ ₀ B ₇ ₁₃ ₀ ₀ ₀ ₀ ₀ ₀ C ₂ ₁₄ ₀ ₀ ₀ ₀ ₀ ₀ D ₁ ₂ ₁ ₂ ₀ ₀ ₀ ₀ E ₉ ₂₀ ₁ ₂ ₀ ₀ ₀ ₀ F ₃₆ ₉ ₀ ₀ ₀ ₀ ₀ ₀ G ₃₄ ₁₀ ₂ ₁ ₀ ₀ ₀ ₀ CONSTITUTIONAL SYMPT A ₂ ₁ ₀ ₀ ₀ ₀ ₀ ₀ B ₀ ₀ ₀ ₀ ₀ ₀ ₀ ₀ C ₀ ₀ ₀ ₀ ₀ ₀ ₀ ₀ D ₀ ₀ ₀ ₀ ₀ ₀ ₀ ₀ E ₁ ₂ ₀ ₀ ₀ ₀ ₂ ₄ F ₂ ₁ ₁ ₀ ₀ ₀ ₀ ₀ G ₂ ₁ ₀ ₀ ₀ ₀ ₀ ₀ Dermatology/Skin ALOPECIA A ₁₅₈ ₄₅ ₀ ₀ ₀ ₀ ₀ ₀ B ₃₃ ₆₀ ₀ ₀ ₀ ₀ ₀ ₀ C ₈ ₅₇ ₀ ₀ ₀ ₀ ₀ ₀ D ₂₇ ₄₅ ₀ ₀ ₀ ₀ ₀ ₀ E ₇ ₁₆ ₀ ₀ ₀ ₀ ₀ ₀ F ₁₃₄ ₃₅ ₀ ₀ ₀ ₀ ₀ ₀ G ₂₂₇ ₆₈ ₀ ₀ ₀ ₀ ₀ ₀ Gastrointestinal ANOREXIA A ₆₅ ₁₈ ₁₅ ₄ ₃ ₁ ₀ ₀ B ₁₁ ₂₀ ₂ ₄ ₀ ₀ ₀ ₀ C ₂ ₁₄ ₁ ₇ ₀ ₀ ₀ ₀ D ₉ ₁₅ ₁ ₂ ₀ ₀ ₀ ₀ E ₁₇ ₃₈ ₁ ₂ ₁ ₂ ₀ ₀ F ₁₀₅ ₂₇ ₆ ₂ ₀ ₀ ₀ ₀ G ₇₅ ₂₂ ₂₀ ₆ ₀ ₀ ₀ ₀ NAUSEA A ₁₈₇ ₅₃ ₅₃ ₁₅ ₀ ₀ ₀ ₀ B ₃₃ ₆₀ ₈ ₁₅ ₀ ₀ ₀ ₀ C ₇ ₅₀ ₆ ₄₃ ₀ ₀ ₀ ₀ D ₃₀ ₅₀ ₃ ₅ ₀ ₀ ₀ ₀ Body System Adverse Event A R M

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NCCTG Status Report for Study N9741 - October 2002

N9741 - Page 9 of 15 GI NCCTG GI Committee E ₃₃ ₇₃ ₆ ₁₃ ₀ ₀ ₀ ₀ F ₂₃₇ ₆₁ ₂₂ ₆ ₀ ₀ ₀ ₀ G ₂₁₄ ₆₄ ₆₈ ₂₀ ₀ ₀ ₀ ₀ STOMATITIS A ₇₉ ₂₂ ₂ ₁ ₁ ₀ ₀ ₀ B ₁₂ ₂₂ ₁ ₂ ₀ ₀ ₀ ₀ C ₂ ₁₄ ₁ ₇ ₀ ₀ ₀ ₀ D ₃₇ ₆₂ ₁ ₂ ₀ ₀ ₀ ₀ E ₁₉ ₄₂ ₁ ₂ ₀ ₀ ₀ ₀ F ₁₄₃ ₃₇ ₁ ₀ ₀ ₀ ₀ ₀ G ₆₅ ₁₉ ₁ ₀ ₀ ₀ ₀ ₀ DEHYDRATION A ₂₀ ₆ ₂₂ ₆ ₄ ₁ ₁ ₀ B ₂ ₄ ₁ ₂ ₀ ₀ ₀ ₀ C ₀ ₀ ₂ ₁₄ ₀ ₀ ₀ ₀ D ₁ ₂ ₁ ₂ ₀ ₀ ₀ ₀ E ₃ ₇ ₃ ₇ ₀ ₀ ₀ ₀ F ₁₅ ₄ ₁₁ ₃ ₁ ₀ ₁ ₀ G ₂₆ ₈ ₁₈ ₅ ₂ ₁ ₂ ₁ COLITIS A ₁ ₀ ₃ ₁ ₀ ₀ ₀ ₀ B ₀ ₀ ₁ ₂ ₀ ₀ ₀ ₀ C ₀ ₀ ₀ ₀ ₀ ₀ ₀ ₀ D ₀ ₀ ₀ ₀ ₀ ₀ ₀ ₀ E ₀ ₀ ₀ ₀ ₀ ₀ ₀ ₀ F ₁ ₀ ₃ ₁ ₀ ₀ ₀ ₀ G ₁ ₀ ₁ ₀ ₀ ₀ ₁ ₀ CONSTIPATION A ₈₈ ₂₅ ₆ ₂ ₃ ₁ ₀ ₀ B ₁₀ ₁₈ ₀ ₀ ₂ ₄ ₀ ₀ C ₀ ₀ ₁ ₇ ₁ ₇ ₀ ₀ D ₉ ₁₅ ₀ ₀ ₀ ₀ ₀ ₀ E ₁₂ ₂₇ ₀ ₀ ₀ ₀ ₀ ₀ F ₉₆ ₂₅ ₁₂ ₃ ₂ ₁ ₀ ₀ G ₆₂ ₁₈ ₁₀ ₃ ₀ ₀ ₀ ₀ ILEUS A ₀ ₀ ₇ ₂ ₄ ₁ ₀ ₀ B ₀ ₀ ₁ ₂ ₀ ₀ ₀ ₀ C ₀ ₀ ₁ ₇ ₀ ₀ ₀ ₀ D ₀ ₀ ₃ ₅ ₀ ₀ ₀ ₀ E ₀ ₀ ₁ ₂ ₀ ₀ ₀ ₀ F ₂ ₁ ₂ ₁ ₃ ₁ ₀ ₀ G ₃ ₁ ₇ ₂ ₃ ₁ ₀ ₀ VOMITING A ₁₀₅ ₃₀ ₃₃ ₉ ₇ ₂ ₀ ₀ Body System Adverse Event A R M