Monoclonal Antibody Therapy in Treating Patients With Metastatic Colorectal Cancer

An Open Label Phase II Clinical Trial To Evaluate The Safety And Efficacy Of ABX-EGF In Patients With Metastatic Colorectal Carcinoma

RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

PURPOSE: Phase II trial to study the effectiveness of monoclonal antibody therapy in treating patients who have relapsed or refractory metastatic colorectal cancer.

OBJECTIVES:

• Determine the response rate of patients with metastatic colorectal cancer treated with monoclonal antibody ABX-EGF.
• Determine the additional measures of clinical efficacy of this drug, in terms of progression-free survival, overall survival, and time to treatment failure, in these patients.
• Determine the safety of this drug in these patients.

OUTLINE: This is a multicenter study.

Patients receive monoclonal antibody ABX-EGF IV over 1 hour weekly on weeks 1-8. Treatment repeats every 8 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed at 4 weeks, every 3 months for 1 year, and then every 6 months for 1 year.

PROJECTED ACCRUAL: A total of 20-100 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed colorectal carcinoma

  • Diagnosed by fine-needle aspirate or tissue biopsy
  • Metastatic disease
  • No squamous cell carcinoma

• Relapsed or refractory after prior chemotherapy with irinotecan and a fluoropyrimidine (i.e., fluorouracil, capecitabine, or ftorafur with or without leucovorin calcium) given concurrently or sequentially

  • Progressive disease within 2 months of last dose of this prior chemotherapy for metastatic disease OR
  • Evidence of relapse within 12 months after last dose of adjuvant therapy

• Bidimensionally measurable disease

• Overexpression of epidermal growth factor r (EGFr) by immunohistochemistry

  • Must be 2+ or 3+ in at least 10% of evaluated tumor cells

• No known brain metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count greater than 1,500/mm3
• Platelet count greater than 100,000/mm3

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST and ALT no greater than 3 times ULN
• Alkaline phosphatase no greater than 3 times ULN

Renal:

• Creatinine no greater than 2.2 mg/dL

Cardiovascular:

• LVEF at least 45% by MUGA
• No myocardial infarction within the past year

Other:

• HIV negative
• No other malignancy within the past 5 years except basal cell carcinoma or carcinoma in situ of the cervix
• No chronic medical or psychiatric condition that would preclude study
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 1 month after study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior EGFr-targeting agents or biological agents with antitumor activity

Chemotherapy:

• See Disease Characteristics
• At least 30 days since prior systemic chemotherapy
• No more than 2 prior fluoropyrimidine regimens (e.g., fluorouracil and leucovorin calcium followed by capecitabine)
• No other prior chemotherapy, except leucovorin calcium, for colorectal carcinoma

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 30 days since prior radiotherapy

Surgery:

• Not specified

Other:

• At least 30 days since other prior anticancer therapy
• No prior investigational drug with potential antitumor activity
• No other concurrent investigational drugs