Irinotecan and Docetaxel With or Without Cetuximab in Treating Patients With Metastatic Pancreatic Cancer

Eastern Cooperative Oncology Group

Status and phase: Completed; Phase 2

Conditions: Pancreatic Cancer

Treatments: Drug: irinotecan hydrochloride; Biological: cetuximab; Drug: docetaxel

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00042939

E8200 [ECOG] (Other Identifier)

CDR0000069486

U10CA021115 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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 .

Full description

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)

Enrollment: 94 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically confirmed metastatic adenocarcinoma of the pancreas

• Sufficient tumor tissue from fine needle aspiration, core biopsy, or open biopsy available for epidermal growth factor receptor testing

• At least 1 unidimensionally measurable primary or metastatic lesionge

• Age of 18 and over

• ECOG performance status 0-1

• Negative pregnancy test

• Fertile patients must use effective contraception

• Creatinine clearance > 60 mL/min

• LVEF normal

• Absolute neutrophil count > 1,500/mm^3

• Platelet count > 100,000/mm^3

• Bilirubin ≤ upper limit of normal (ULN)*

• SGOT or SGPT and alkaline phosphatase must meet the criteria for 1 of the following*:

  • SGOT or SGPT ≤ 2.5 times ULN AND alkaline phosphatase ≤ ULN
  • SGOT or SGPT ≤ 1.5 times ULN AND alkaline phosphatase > ULN but ≤ 2.5 times ULN
  • SGOT or SGPT ≤ ULN AND alkaline phosphatase > 2.5 but ≤ 4 times ULN

NOTE: *Percutaneous stenting or endoscopic retrograde cholangiopancreatography may be used to normalize liver function tests

Exclusion criteria

• History of uncontrolled arrhythmias
• History of congestive heart failure
• History of uncontrolled angina pectoris
• Prior chemotherapy
• Pre-existing neuropathy ≥ grade 2
• Prior hypersensitivity to polysorbate 80
• Pregnant or nursing

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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94 participants in 2 patient groups

Irinotecan/Docetaxel

Active Comparator group

Description:

Docetaxel was administered intravenously over 60 minutes at a dose of 35 mg/m². 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. Chemotherapy was administered once a week (days 1, 8, 15, 22) for 4 consecutive weeks followed by 2 weeks rest. This constituted a cycle of treatment. Patients were evaluated after 2 cycles.

Treatment:

Drug: docetaxel

Drug: irinotecan hydrochloride

Irinotecan/Docetaxel/Cetuximab

Experimental group

Description:

Patients received Cetuximab intravenously once a week for 6 weeks. On day 1 of cycle 1 only, an initial dose of 400 mg/m² (over 120 minutes) was administered. Thereafter, a once-a-week maintenance dose of 250 mg/m² (infused over 60 minutes), was given. The infusion rate never exceeded 5 ml/minute. On the day of the initial dose, the administration of Cetuximab was followed by the administration of docetaxel, after a 60-minute observation period. (The observation period was 30 minutes following maintenance doses.) Docetaxel was administered intravenously over 60 minutes at a dose of 35 mg/m². 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. Chemotherapy was administered once a week (days 1, 8, 15, 22) for 4 consecutive weeks followed by 2 weeks rest. Cetuximab was administered once a week for 6 consecutive weeks. A cycle of treatment was 6 weeks.

Treatment:

Drug: docetaxel

Biological: cetuximab

Drug: irinotecan hydrochloride