gefitinib in treating patients with recurrent metastatic colorectal cancer

Conditions: Colorectal Cancer

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.

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

Keywords: stage iv colon cancer stage iv rectal cancer recurrent colon cancer recurrent rectal cancer adenocarcinoma of the colon adenocarcinoma of the rectum