Cetuximab, Gemcitabine, and Oxaliplatin in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer

OBJECTIVES:

Primary

• Determine the progression-free survival of patients with locally advanced or metastatic pancreatic cancer treated with cetuximab, gemcitabine hydrochloride, and oxaliplatin.

Secondary

• Determine the complete response and partial response in patients treated with this regimen.
• Determine the time to progression in patients treated with this regimen.
• Determine the duration of response in patients treated with this regimen.
• Determine the survival of patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.

OUTLINE: This is a nonrandomized, open-label, pilot study.

Patients receive cetuximab IV over 1-2 hours on days 1 and 8, gemcitabine hydrochloride IV over 100 minutes on day 1, and oxaliplatin IV over 2-4 hours on day 2. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed pancreatic cancer
• Locally advanced or metastatic disease
• No active CNS metastases

• Patients with stable CNS disease, who have undergone radiotherapy within the past 4 weeks and who have been on a stable dose of corticosteroids for > 3 weeks, are eligible

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 1.5 mg/dL
• Alkaline phosphatase ≤ 3 times upper limit of normal (ULN) (5 times ULN if known hepatic metastases)
• AST and ALT ≤ 3 times ULN (5 times ULN if known hepatic metastases)
• Creatinine ≤ 1.5 mg/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 90 days after completion of study treatment
• No significant history of uncontrolled cardiac disease, including any of the following:

• Uncontrolled hypertension
• Unstable angina
• Myocardial infarction within the past 6 months
• Uncontrolled congestive heart failure
• Cardiomyopathy with decreased ejection fraction
• No prior severe infusion reaction to a monoclonal antibody
• No active infection or fever ≥ 38.5°C within the past 3 days
• No known hypersensitivity to any components of gemcitabine hydrochloride, oxaliplatin, or to a monoclonal antibody
• No peripheral neuropathy ≥ grade 2
• No known HIV positivity
• No hepatitis B or C infection (active, previously treated, or both)
• No other medical condition, including mental illness or substance abuse, that would preclude study compliance

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from all prior therapy, including surgery
• More than 30 days since prior investigational therapy
• More than 4 weeks since prior radiotherapy
• No prior radiotherapy to more than 25% of bone marrow
• More than 30 days since prior chemotherapy
• No prior chemotherapy for metastatic pancreatic cancer
• Prior fluoropyrimidine as a radiosensitizer allowed
• Prior gemcitabine hydrochloride in the adjuvant setting allowed
• No prior therapy that specifically and directly targets the epidermal growth factor receptor (EGFR) pathway
• No prior allogeneic transplantation
• No other concurrent investigational therapy, chemotherapy, or systemic antineoplastic therapy
• No other concurrent treatment that targets the EGFR
• No other concurrent monoclonal antibody therapy
• No concurrent radiotherapy except for local control of bone pain