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

Pancreatic Cancer Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00042939
• Other study ID #: CDR0000069486
• Secondary ID: U10CA021115E8200
• Status: Completed
• Phase: Phase 2
• Start date: December 9, 2003
• Est. completion date: August 2009

Study information

• Verified date: June 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 .

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 94
• Est. completion date: August 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

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.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Eastern Cooperative Oncology Group	National Cancer Institute (NCI)

References & Publications (2)

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 recepto

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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