RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as cetuximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining chemotherapy with cetuximab may kill more tumor cells. PURPOSE: This randomized phase II trial is studying giving irinotecan and docetaxel together with cetuximab to see how well it works compared to irinotecan and docetaxel alone in treating patients with metastatic pancreatic cancer .
OBJECTIVES: * Determine the efficacy of irinotecan and docetaxel with or without cetuximab, in terms of objective response rate, in patients with metastatic adenocarcinoma of the pancreas. * Determine the time to progression and overall survival of patients treated with these regimens. * Determine the proportion of patients with tumors that overexpress epidermal growth factor receptor. OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms. * Arm A: Patients receive docetaxel IV over 1 hour and irinotecan IV over 30 minutes weekly on days 1, 8, 15, and 22. * Arm B: Patients receive docetaxel and irinotecan as in arm A. Patients also receive cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, and 36. Courses repeat in both arms every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years, every 6 months for 1 year, and then periodically thereafter. PROJECTED ACCRUAL: A total of 92 patients (46 per treatment arm)
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
94
Patients received cetuximab intravenous infusions, via infusion pump or syringe pump, once a week for 6 weeks.
Docetaxel was administered intravenously over 60 minutes at a dose of 35 mg/m² once a week (days 1, 8, 15, 22) for 4 consecutive weeks followed by 2 weeks rest. Docetaxel was diluted in 100-150 ml of infusion solution.
After the completion of the docetaxel infusion, irinotecan was administered intravenously over 30 minutes at a dose of 50 mg/m² once a week (days 1, 8, 15, 22) for 4 consecutive weeks followed by 2 weeks rest.
Proportion of Patients With Objective Response Evaluated by RECIST (Solid Tumor Response Criteria)
Per RECIST criteria, Complete response (CR)= disappearance of all target and nontarget lesions Partial response (PR)= \>=30% decrease in the sum of the longest diameters of target lesions from baseline, and persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits. Objective response = CR + PR
Time frame: Assessed every 12 weeks until progression
Progression-free Survival
Progression-free survival was defined as the shorter of: 1. The time from registration to progression. or 2. The time from registration to death without documentation of progression given that the death occured within 4 months of the last disease assessment without progression (or registration, whichever is more recent). Progression is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s) or unequivocal progression of existing nontarget lesions.
Time frame: Assessed every 3 months for 2 years and then every 6 months for 1 year
Overall Survival
Overall survival was defined as time from registration to death from any cause.
Time frame: Assessed every 3 months for 2 years and then every 6 months for 1 year
Epidermal Growth Factor Receptor (EGFR) Status
EGFR expression was be evaluated by staining 5-micron paraffin sections of tumor biopsies with anti-EGFR clone 2-18C9 (DAKO Corporation, Carpinteria, CA) using an indirect immunoperoxidase technique according to the instructions provided by DAKO. In brief, this includes an antigen retrieval pretreatment, the blocking of endogenous peroxidase activity, incubation with anti-EGFR antibody or a negative reagent control, staining with a detection system, visualization, and coverslipping.
Time frame: Original tumor tissue samples submitted within one month of patient randomization
Proportion of Patients With Thromboembolic Events
To determine the rate of thromboembolic events in this population when prophylactic enoxaparin sodium is administered.
Time frame: Assessed every 6 weeks while on treatment and for 30 days after the end of treatment
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