S0205 Gemcitabine w/ or w/o Cetuximab as First-Line Therapy in Locally Advanced Pancreas Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies, such as cetuximab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known whether gemcitabine is more effective with or without cetuximab in treating pancreatic cancer. PURPOSE: This randomized phase III trial is studying giving gemcitabine together with cetuximab to see how well it works compared to giving gemcitabine alone as first-line therapy in treating patients with locally advanced unresectable or metastatic adenocarcinoma of the pancreas.

Detailed Description
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OBJECTIVES: Compare the overall survival of patients with locally advanced unresectable or metastatic adenocarcinoma of the pancreas treated with gemcitabine and cetuximab vs gemcitabine alone. Compare the time to treatment failure in patients treated with these regimens. Estimate the percentage of patients with epidermal growth factor receptor (EGFR) tumor expression in patients treated with these regimens. Compare the overall survival of patients in the EGFR-positive subset treated with these regimens. Compare the toxicity of these regimens in these patients. Compare the total response rate (confirmed and unconfirmed complete and partial response) in patients with measurable disease treated with these regimens. Compare the patient report of pain and quality of life of patients treated with these regimens. OUTLINE: This is an open-label, randomized, multicenter study. Patients are stratified according to disease status (locally advanced unresectable vs metastatic), Zubrod performance status (0 or 1 vs 2), and prior pancreatectomy (yes vs no). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, and 22 and gemcitabine IV over 30 minutes on days 1, 8, 15, and 22 for course 1 and days 1, 8, and 15 for all subsequent courses. Arm II: Patients receive gemcitabine as in arm I. In both arms, courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, before each course, and at the end of study therapy. Patients are followed every 6 months for 2 years and then annually for 1 year. PROJECTED ACCRUAL: A total of 704 patients (352 per treatment arm) will be accrued for this study within 5 years.

Official Title
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A Phase III Randomized Open-Label Study Comparing Gemcitabine Plus Cetuximab (IMC-C225) Versus Gemcitabine As First-Line Therapy Of Patients With Advanced Pancreas Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Biological: cetuximab
* Drug: gemcitabine hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically* or cytologically confirmed pancreatic adenocarcinoma meeting 1 of the following criteria: Locally advanced unresectable disease Distant metastatic disease NOTE: If diagnosis is based on a metastatic site the histology must be compatible with pancreatic cancer Measurable or nonmeasurable disease by x-ray, scan, or physical examination Tumor tissue must be submitted for evaluation of epidermal growth factor receptor expression before study entry None of the following tumor types are allowed: Endocrine tumors Lymphoma of the pancreas Ampullary cancer No known brain metastases PATIENT CHARACTERISTICS: Age Not specified Performance status Zubrod 0-2 Life expectancy At least 3 months Hematopoietic Absolute granulocyte count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic Bilirubin no greater than 2.0 times upper limit of normal (ULN) SGOT or SGPT no greater than 2.5 times ULN Renal Creatinine no greater than 2.0 mg/dL Cardiovascular No significant history of cardiac disease No uncontrolled hypertension No unstable angina No uncontrolled arrhythmia No congestive heart failure Other Not pregnant or nursing Fertile patients must use effective contraception HIV negative No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer that is currently in remission PRIOR CONCURRENT THERAPY: Biologic therapy No prior immunotherapy for advanced pancreatic cancer No prior cetuximab or other therapy that targets the epidermal growth factor pathway No prior chimerized or murine monoclonal antibody therapy No other concurrent anticancer immunotherapy Chemotherapy At least 6 months since prior adjuvant chemotherapy No prior chemotherapy or chemoradiotherapy for advanced pancreatic cancer No prior gemcitabine No other concurrent anticancer chemotherapy Endocrine therapy No prior hormonal therapy for advanced pancreatic cancer No concurrent anticancer hormonal therapy Radiotherapy See Chemotherapy At least 28 days since prior radiotherapy and recovered Prior palliative radiotherapy to metastatic sites allowed No concurrent anticancer radiotherapy, including whole brain radiotherapy for progressive disease (i.e., CNS metastasis) Surgery At least 14 days since prior pancreatic cancer surgery and recovered Other No other concurrent anticancer therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: gemcitabine hydrochloride + IMC-C225<br>Loading dose: gemcitabine hydrochloride 1000mg/m2, IV on Day 1; Cetuxiumab 400mg/m2, IV on Day 1 (cycle 1 only) Weekly maintenance: Cetuximab 250mg/m2, IV on Days 8,15,22 of cycle 1 & days 1,8,15,22 of all subsequent cycles; gemcitabine hydrochloride 1000mg/m2, IV on Days 8,15,22 of cycle 1 and Days 1,8,15 of all subsequent cycles. | Biological: cetuximab<br>* Loading dose: Cetuxiumab 400mg/m2, IV on Day 1 (cycle 1 only). Weekly maintenance: Cetuximab 250mg/m2, IV on Days 8,15,22 of cycle 1 & days 1,8,15,22 of all subsequent cycles<br>Drug: gemcitabine hydrochloride<br>* 1000mg/m2 IV over 30 minutes<br>|
| Experimental: gemcitabine hydrochloride alone<br>gemcitabine hydrochloride 1000mg/m2, IV on Days 1,8,15,22 of cycle 1 and Days 1,8,15 of all subsequent cycles. | Drug: gemcitabine hydrochloride<br>* 1000mg/m2 IV over 30 minutes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival comparison between treatment groups |  | every 4 weeks for 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate comparison between treatment groups as measured by RECIST and radiological evaluation at every other course |  | every 9 weeks until progression | 
| Time to treatment failure comparison between groups from registration to first observation of progressive disease, symptomatic deterioration, or death |  | every 4 weeks while on treatment | 
| Percentage of patients with EGFR tumor expression and compare overall survival of patients in the EGFR subset |  | every 4 weeks for 3 years | 
| Toxicity profile comparison of patients treated with 2 regimens and measured until 30 days after completion of study treatment |  | every 4 weeks while on treatment | 
| Total response rate comparison between treatment groups in the subset of patients with measurable disease by RECIST at every other course |  | every 9 weeks until progression | 
| Pain and quality of life comparison between treatment groups as measured by patient questionnaire at baseline, before each course, and then completion of study treatment |  | every 4 weeks while on treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the pancreas, stage III pancreatic cancer, stage IV pancreatic cancer