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

Phase II Trial of Irinotecan/Docetaxel for Advanced Pancreatic Cancer, With Randomization Between Irinotecan/Docetaxel and Irinotecan/Docetaxel Plus C225 a Monoclonal Antibody to the Epidermal Growth Factor Receptor (EGF-r)

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 .

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: docetaxel; Drug: irinotecan hydrochloride; Biological: cetuximab

Detailed 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)

• Study Type: Interventional
• Enrollment (Actual): 94
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Irinotecan/Docetaxel; 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.	Drug: docetaxel; 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.; Other Names: Taxotere; Drug: irinotecan hydrochloride; 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.; Other Names: Camptosar
Experimental: Irinotecan/Docetaxel/Cetuximab; 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.	Drug: docetaxel; 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.; Other Names: Taxotere; Drug: irinotecan hydrochloride; 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.; Other Names: Camptosar; Biological: cetuximab; Patients received cetuximab intravenous infusions, via infusion pump or syringe pump, once a week for 6 weeks.; Other Names: C225; Erbitux

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Assessed every 12 weeks until progression

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	Progression-free survival was defined as the shorter of: The time from registration to progression. or; 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.	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.	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.	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.	Assessed every 6 weeks while on treatment and for 30 days after the end of treatment

Collaborators and Investigators

• Sponsor: Eastern Cooperative Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Barbara A. Burtness, MD, Fox Chase Cancer Center

Publications and helpful links

General Publications

• Burtness BA, Powell ME, Berlin JD, et al.: Phase II ECOG trial of irinotecan/docetaxel with or without cetuximab in metastatic pancreatic cancer: updated survival and CA19-9 results. [Abstract] J Clin Oncol 26 (Suppl 15): A-4642, 2008.
• Burtness BA, Powell M, Berlin J, et al.: Phase II trial of irinotecan/docetaxel for advanced pancreatic cancer with randomization between irinotecan/docetaxel and irinotecan/docetaxel plus C225, a monoclonal antibody to the epidermal growth factor receptor (EGF-r) : Eastern Cooperative Oncology. [Abstract] J Clin Oncol 25 (Suppl 18): A-4519, 2007.

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2003
• Primary Completion (Actual): June 1, 2009
• Study Completion (Actual): August 1, 2009

Study Registration Dates

• First Submitted: August 5, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimated): January 27, 2003

Study Record Updates

• Last Update Posted (Actual): July 6, 2023
• Last Update Submitted That Met QC Criteria: June 21, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: pancreatic cancer; metastatic pancreatic cancer; irinotecan; EGF-r; docetaxel; cetuximab
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Topoisomerase I Inhibitors; Docetaxel; Irinotecan; Cetuximab
• Other Study ID Numbers: CDR0000069486; U10CA021115 (U.S. NIH Grant/Contract); E8200 [ECOG] (Other Identifier: Eastern Cooperative Oncology Group (ECOG))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No