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

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies, such as cetuximab and trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving cetuximab together with trastuzumab may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of trastuzumab when given together with cetuximab and to see how well it works in treating patients with metastatic pancreatic cancer that progressed after previous treatment with gemcitabine.

Detailed Description
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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.

Official Title
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Phase I-II Study Evaluating Combined Treatment of Cetuximab and Trastuzumab in Metastatic Pancreatic Cancer Patients Progressing After Gemcitabine Based Chemotherapy.(THERAPY)

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: cetuximab
* Drug: trastuzumab


Participation Criteria
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Eligibility Criteria
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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

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: cetuximab, trastuzumab<br> | Drug: cetuximab<br>* Cetuximab at the initial dose of 400 mg/m² (J1S1) as a 2-hour infusion and then at the 250 mg/m² dose as a 1-hour infusion in subsequent weeks.<br>Drug: trastuzumab<br>* Two dose levels of trastuzumab will be evaluated for Phase 1: Level 1: a loading dose of 3 mg/kg as a 90-minute intravenous infusion at J1S1 and then 1.5 mg/kg as a 30-minute intravenous infusion for all subsequent weekly administrations; Level 2: a loading dose of 4 mg/kg as a 90-minute intravenous infusion at J1S1 and then 2 mg/kg as a 30-minute intravenous infusion for all subsequent weekly administrations.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recommended dose of trastuzumab when given with cetuximab (Phase I) | From baseline to the end of treatment | 15 days | 
| Objective response rate as assessed by RECIST criteria (Phase II) | From baseline to the end of treatment | Approximately 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | From baseline to the end of study | Approximately 36 months | 
| Overall survival | From baseline to the end of study | Approximately 36 months | 

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