Pancreatic Cancer
Conditions
Keywords
stage IV pancreatic cancer, recurrent pancreatic cancer, adenocarcinoma of the pancreas
Brief summary
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
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.
Interventions
DRUGcetuximab
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.
DRUGtrastuzumab
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.
Sponsors
Institut du Cancer de Montpellier - Val d'Aurelle
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recommended dose of trastuzumab when given with cetuximab (Phase I) | 15 days | From baseline to the end of treatment |
| Objective response rate as assessed by RECIST criteria (Phase II) | Approximately 8 weeks | From baseline to the end of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival | Approximately 36 months | From baseline to the end of study |
| Overall survival | Approximately 36 months | From baseline to the end of study |
Countries
France
Outcome results
None listed