Cetuximab and Trastuzumab in Treating Patients With Metastatic Pancreatic Cancer That Progressed After Previous Treatment With Gemcitabine

OBJECTIVES:

Primary

• Determine the recommended dose of trastuzumab when given with cetuximab in patients with metastatic pancreatic cancer that progressed after gemcitabine-based chemotherapy. (Phase I)
• Evaluate the objective response rate as assessed by RECIST criteria. (Phase II)

Secondary

• Evaluate the safety profile as assessed by NCI CTCAE v3.0.
• Evaluate progression-free survival.
• Evaluate overall survival.

OUTLINE: This is a multicenter, phase I dose-escalation study of trastuzumab followed by a phase II study.

Patients receive cetuximab IV over 1-2 hours and trastuzumab IV over 30-90 minutes on day 1. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

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

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic adenocarcinoma of the pancreas

• Progressed after first-line or adjuvant gemcitabine-based chemotherapy
• Measurable disease as assessed by RECIST criteria
• No known brain metastasis or symptomatic carcinomatous leptomeningitis

PATIENT CHARACTERISTICS:

• WHO performance status 0-1
• Life expectancy ≥ 3 months
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9 g/dL
• Creatinine ≤ 1.5 times upper limit of normal (ULN)
• Total bilirubin ≤ 2.5 times ULN
• ALT/AST ≤ 5 times ULN
• LVEF ≥ 55%
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No significant comorbidities, including any of the following:

• Cardiovascular disease
• Documented history of congestive heart failure
• Uncontrolled, high-risk arrhythmia
• Angina pectoris requiring treatment
• Clinically significant valvular disease
• Evidence of transmural myocardial infarction by ECG
• Uncontrolled hypertension
• Active bleeding
• Clinically significant active infection
• Severe dyspnea at rest
• Oxygen-dependency
• No other malignancy except basal cell carcinoma of the skin
• No severe hypersensitivity to cetuximab or trastuzumab
• No medical or psychological condition that would preclude study completion or giving informed consent
• No legal incapacity or limited legal capacity

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior cetuximab or trastuzumab
• No other concurrent experimental drugs or anticancer therapy