Irinotecan And Docetaxel With Or Without Cetuximab In Treating Patients With Metastatic Pancreatic Cancer

Study Overview

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

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)

Pancreatic Cancer

BIOLOGICAL: cetuximab
DRUG: docetaxel
DRUG: irinotecan hydrochloride

CDR0000069486
U10CA021115 (U.S. NIH Grant/Contract)
E8200 [ECOG] (OTHER Identifier) (OTHER: Eastern Cooperative Oncology Group (ECOG))

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2002-08-05	Results First Submitted 2011-06-21	Last Update Submitted that met QC Criteria 2023-06-21
First Submitted that Met QC Criteria 2003-01-26	Results First Submitted that Met QC Criteria 2011-06-21	Last Update Posted (ACTUAL) 2023-07-06
First Posted (ACTUAL) 2003-01-27	Results First Posted 2011-07-19	Last Verified 2023-06

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
None

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 o	BIOLOGICAL: cetuximab Patients received cetuximab intravenous infusions, via infusion pump or syringe pump, once a week for 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. 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.
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. Th	BIOLOGICAL: cetuximab Patients received cetuximab intravenous infusions, via infusion pump or syringe pump, once a week for 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. 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.

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 o

BIOLOGICAL: cetuximab

Patients received cetuximab intravenous infusions, via infusion pump or syringe pump, once a week for 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.

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.

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. Th

BIOLOGICAL: cetuximab

Patients received cetuximab intravenous infusions, via infusion pump or syringe pump, once a week for 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.

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.

Primary Outcome Measures	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	Measure Description	Time Frame
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.	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

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Cancer Institute (NCI)

Investigators

STUDY_CHAIR: Barbara A. Burtness, MD, Fox Chase Cancer Center

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

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.

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