Gefitinib in Treating Patients With Recurrent Metastatic Colorectal Cancer

Colorectal Cancer Clinical Trial

Official title:

A Randomized Phase II Trial of Two Dose Levels of ZD1839 (Iressa) (NSC 715055, IND 61187) in Patients With Recurrent Colorectal Adenocarcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00025350
• Other study ID #: CDR0000068952
• Secondary ID: E-6200
• Status: Completed
• Phase: Phase 2
• First received: October 11, 2001
• Last updated: June 20, 2013
• Start date: October 2001
• Est. completion date: June 2006

Study information

• Verified date: January 2006
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: June 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• gefitinib

Locations

Country	Name	City	State
United States	Robert H. Lurie Comprehensive Cancer Center, Northwestern University	Chicago	Illinois
United States	Veterans Affairs Medical Center - Lakeside Chicago	Chicago	Illinois
United States	Ireland Cancer Center	Cleveland	Ohio
United States	CCOP - Central Illinois	Decatur	Illinois
United States	CCOP - Evanston	Evanston	Illinois
United States	CCOP - Merit Care Hospital	Fargo	North Dakota
United States	CCOP - Kalamazoo	Kalamazoo	Michigan
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	Veterans Affairs Medical Center - Madison	Madison	Wisconsin
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus	Nashville	Tennessee
United States	Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	NYU School of Medicine's Kaplan Comprehensive Cancer Center	New York	New York
United States	Veterans Affairs Medical Center - New York	New York	New York
United States	University of Pennsylvania Cancer Center	Philadelphia	Pennsylvania
United States	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania

Sponsors (2)

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

Country where clinical trial is conducted

United States, 

References & Publications (2)

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 — View Citation

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 Coop