PhI Study of Erbitux & Gemcitabine w/Radiation Therapy for Locally Adv. Pancreas Ca

OBJECTIVES:

• Determine the maximum tolerated dose of gemcitabine hydrochloride when administered with cetuximab and radiotherapy in patients with unresectable locally advanced pancreatic or periampullary region cancer.
• Determine the toxicity of this regimen in these patients.

OUTLINE: This is a dose-escalation study of gemcitabine hydrochloride.

Patients receive cetuximab IV over 1-2 hours once weekly in weeks 1-7 and gemcitabine hydrochloride IV over 15-40 minutes once weekly in weeks 2-7. Patients also undergo radiotherapy 5 days a week in weeks 2-7. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of gemcitabine hydrochloride until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

After completion of study treatment, patients are followed for 30 days and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 12-30 patients will be accrued for this study.

Inclusion criteria

• Histologically confirmed adenocarcinoma of the pancreas (head, body, or tail) or periampullary region, meeting both of the following criteria:

• Unresectable disease
• Locally advanced disease
• Measurable or evaluable disease by CT scan or MRI
• No evidence of metastatic disease outside of the planned irradiation field
• ECOG performance status 0-2
• WBC ≥ 3,000/mm³
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 8.5 g/dL
• AST and ALT ≤ 5 times upper limit of normal
• Bilirubin ≤ 2.0 mg/dL
• Creatinine ≤ 2.0 mg/dL
• No clinical indication of compromised function of nonirradiated kidney
• No secondary malignancies within the past 5 years except for resected nonmelanoma skin cancer or carcinoma in situ of the cervix
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

Exclusion criteria

• No acute hepatitis
• No known HIV infection
• No other active or uncontrolled infection
• No significant history of uncontrolled cardiac disease, including any of the following:

• Hypertension
• Unstable angina
• Myocardial infarction within the past 6 months
• Congestive heart failure
• Cardiomyopathy with decreased ejection fraction
• No prior severe infusion reaction to a monoclonal antibody

PRIOR CONCURRENT THERAPY:

• No prior radiotherapy to planned field of treatment
• No prior therapy that specifically and directly targets EGFR pathway
• At least 14 days since prior surgery or biopsy
• At least 28 days since prior bypass procedures
• More than 5 years since prior and no other concurrent chemotherapy
• No other concurrent investigational agent