Patient case: 49-year-old male with colorectal cancer; genetic feature: NRAS

Clinical trial: Gefitinib in Treating Patients With Recurrent Metastatic 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.

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: 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

Relevance to patient case: not relevant