Gefitinib in Treating Patients With Recurrent Metastatic Colorectal Cancer

NCT ID: NCT00025350

Last Updated: 2013-06-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-10-31
• Study Completion Date: 2006-06-30

Brief Summary

RATIONALE: Biological therapies such as gefitinib may interfere with the growth of the tumor cells and slow the growth of recurrent metastatic colorectal cancer.

PURPOSE: Randomized phase II trial to compare the effectiveness of two different doses of gefitinib in treating patients who have recurrent metastatic colorectal cancer.

Detailed Description

OBJECTIVES:

• Determine the 4-month progression-free survival rate in patients with recurrent metastatic colorectal adenocarcinoma treated with gefitinib.
• Determine the objective tumor response rate, progression, and overall survival of patients treated with this drug.
• Determine the toxicity of this drug in these patients.

OUTLINE: This is a randomized, double-blind study. Patients are stratified according to ECOG performance status (0-1 vs 2), baseline serum CEA (less than 5 mg/L vs at least 5 mg/L), and number of metastatic sites (1 vs 2 or more). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral gefitinib once daily (twice daily on day 1 of course 1). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive a higher dose of oral gefitinib as in arm I. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 100 patients (50 per treatment arm) will be accrued for this study.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Interventions

gefitinib

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically proven adenocarcinoma of the colon or rectum
• Measurable disease
• Evidence of new or progressive metastatic disease within 6 months of last treatment
• Must have received prior systemic treatment with fluorouracil (and/or its analogs, with or without leucovorin calcium or levamisole) and irinotecan in the adjuvant or metastatic setting
• Metastatic tumor site accessible for biopsy
• No known brain metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• More than 12 weeks

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST or ALT no greater than 2.5 times ULN (5 times ULN if tumor involvement of the liver)

Renal:

• Creatinine no greater than 1.5 times ULN OR
• Creatinine clearance at least 60 mL/min

Cardiovascular:

• No New York Heart Association class III or IV heart disease
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No ongoing active or uncontrolled infections
• Other prior malignancies allowed provided prior therapy is discontinued and no evidence of disease
• No other uncontrolled illness or psychiatric illness/social situations that would preclude study
• Must be able to take and retain oral medications

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior signal transduction inhibitors (e.g., vascular endothelial growth factor-, vascular endothelial growth factor receptor-, and epidermal growth factor receptor-targeted agents) for colorectal cancer

Chemotherapy:

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy and recovered
• No other prior cytotoxic chemotherapy (e.g., oxaliplatin) for colorectal cancer

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior radiotherapy and recovered

Surgery:

• Not specified

Other:

• No other prior systemic therapy for colorectal cancer
• No other prior investigational or approved agents for colorectal cancer
• No other concurrent investigational agents
• No concurrent antiretroviral therapy for HIV-positive patients

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Eastern Cooperative Oncology Group

NETWORK

Sponsor Role: lead

Principal Investigators

Mace L. Rothenberg, MD, FACP

Role: STUDY_CHAIR

Vanderbilt-Ingram Cancer Center

Locations

Robert H. Lurie Comprehensive Cancer Center, Northwestern University

Chicago, Illinois, United States

Veterans Affairs Medical Center - Lakeside Chicago

Chicago, Illinois, United States

CCOP - Central Illinois

Decatur, Illinois, United States

CCOP - Evanston

Evanston, Illinois, United States

CCOP - Kalamazoo

Kalamazoo, Michigan, United States

Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Veterans Affairs Medical Center - New York

New York, New York, United States

NYU School of Medicine's Kaplan Comprehensive Cancer Center

New York, New York, United States

CCOP - Merit Care Hospital

Fargo, North Dakota, United States

Ireland Cancer Center

Cleveland, Ohio, United States

University of Pennsylvania Cancer Center

Philadelphia, Pennsylvania, United States

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, United States

Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus

Nashville, Tennessee, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Veterans Affairs Medical Center - Madison

Madison, Wisconsin, United States

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, United States

Countries

United States

References

Rothenberg ML, LaFleur B, Levy DE, Washington MK, Morgan-Meadows SL, Ramanathan RK, Berlin JD, Benson AB 3rd, Coffey RJ. Randomized phase II trial of the clinical and biological effects of two dose levels of gefitinib in patients with recurrent colorectal adenocarcinoma. J Clin Oncol. 2005 Dec 20;23(36):9265-74. doi: 10.1200/JCO.2005.03.0536.

Reference Type: RESULT

PMID: 16361624 (View on PubMed)

Rothenberg ML, Lafleur B, Washington MK, et al.: Changes in epidermal growth factor receptor signaling in serum and tumor biopsies obtained from patients with progressive metastatic colorectal cancer (MCRC) treated with gefitinib (ZD1839): an Eastern Cooperative Oncology Group study. [Abstract] J Clin Oncol 22 (Suppl 14): A-3000, 195s, 2004.

Reference Type: RESULT

Other Identifiers

E-6200

Identifier Type: -

Identifier Source: secondary_id

CDR0000068952

Identifier Type: -

Identifier Source: org_study_id