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

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.

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