Clinical trial NCT00025350: Gefitinib in Treating Patients With Recurrent Metastatic Colorectal Cancer
Official title: A Randomized Phase II Trial of Two Dose Levels of ZD1839 (Iressa) (NSC 715055, IND 61187) in Patients With Recurrent Colorectal Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer
adenocarcinoma of the colon
adenocarcinoma of the rectum
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-10-22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center, Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Veterans Affairs Medical Center - Lakeside Chicago
state: Illinois
city: Decatur
country: United States
facility: CCOP - Central Illinois
state: Illinois
city: Evanston
country: United States
facility: CCOP - Evanston
state: Illinois
city: Kalamazoo
country: United States
facility: CCOP - Kalamazoo
state: Michigan
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey
state: New Jersey
city: New York
country: United States
facility: Veterans Affairs Medical Center - New York
state: New York
city: New York
country: United States
facility: NYU School of Medicine's Kaplan Comprehensive Cancer Center
state: New York
city: Fargo
country: United States
facility: CCOP - Merit Care Hospital
state: North Dakota
city: Cleveland
country: United States
facility: Ireland Cancer Center
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute
state: Pennsylvania
city: Nashville
country: United States
facility: Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Madison
country: United States
facility: Veterans Affairs Medical Center - Madison
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Comprehensive Cancer Center
state: Wisconsin
Study officials:
affiliation: Vanderbilt-Ingram Cancer Center
name: Mace L. Rothenberg, MD, FACP
role: STUDY_CHAIR
References:
citation: 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.
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 Cooperative Oncology Group study. [Abstract] J Clin Oncol 22 (Suppl 14): A-3000, 195s, 2004.