RATIONALE: Monoclonal antibodies such as ABX-EGF 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 ABX-EGF in treating patients who have metastatic colorectal cancer that has not responded to previous chemotherapy.

Condition	Treatment or Intervention	Phase
adenocarcinoma of the colon adenocarcinoma of the rectum recurrent colon cancer stage IV colon cancer recurrent rectal cancer Stage IV rectal cancer	Drug: monoclonal antibody ABX-EGF  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: monoclonal antibody therapy	Phase II

OBJECTIVES: Primary

• Determine the objective response rate and duration of response through week 16 of study treatment in patients with metastatic colorectal cancer treated with monoclonal antibody ABX-EGF after failing prior chemotherapy comprising fluoropyrimidine, irinotecan, and oxaliplatin.

Secondary

• Determine the objective response rate throughout the study, time to response, duration of stable disease, time to disease progression, time to treatment failure, and progression-free and overall survival time of patients treated with this drug.
• Determine change in patient-reported outcomes in patients treated with this drug.
• Determine the safety profile of this drug in these patients.

OUTLINE: This is an open-label, multicenter study.

Patients receive monoclonal antibody ABX-EGF IV over 1 hour once every other week (i.e., weeks 1, 3, 5, 7, etc.). Treatment continues for 60 weeks in the absence of disease progression, unacceptable toxicity, or a human anti-human antibody response.

Quality of life is assessed at baseline, once monthly during study treatment, and 4 weeks after completion of study treatment.

Patients are followed at 4 weeks and then every 3 months for 2 years.

PROJECTED ACCRUAL: A total of 300 patients will be accrued for this study within 5 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed colorectal adenocarcinoma
• Metastatic disease
• Diagnostic tissue obtained by tissue biopsy
• Documented radiographic evidence of disease progression during or after chemotherapy comprising fluoropyrimidine, irinotecan, and oxaliplatin within the past 6 months
• Must have received at least 2, but no more than 3, prior chemotherapy regimens for metastatic colorectal cancer
• Bidimensionally measurable disease
• At least 20 mm by CT scan, MRI, or spiral CT scan
• Tumor expressing epidermal growth factor receptor by immunohistochemistry
• Staining must be positive in ≥ 10% of evaluated tumor cells
• No symptomatic brain metastases requiring treatment

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• AST and ALT ≤ 3 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
• Bilirubin ≤ 2 times ULN

Renal

• Creatinine < 2 mg/dL

Cardiovascular

• LVEF ≥ 45% by echocardiogram or MUGA
• No myocardial infarction within the past year

Pulmonary

• No interstitial pneumonitis or pulmonary fibrosis by CT scan

Other

• HIV negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after study participation
• No allergy to the ingredients of the study drug or to Staphylococcus aureus protein A
• No chronic medical condition, unresolved complication, or laboratory abnormality that would preclude study participation
• No psychiatric illness that would preclude study compliance
• No other disorder that would preclude study consent or participation
• No other active malignancy within the past 5 years except basal cell carcinoma in situ of the cervix or surgically cured malignancy

PRIOR CONCURRENT THERAPY: Biologic therapy

• More than 30 days since prior treatment with any approved antitumor small molecules or biologic agents of short (< 1 week) serum and tissue half-life
• More than 3 months since prior experimental or approved proteins or antibodies

Chemotherapy

• See Disease Characteristics
• More than 30 days since prior systemic chemotherapy
• No prior chemotherapy for metastatic colorectal cancer except fluoropyrimidine, irinotecan, or oxaliplatin*
• Prior leucovorin calcium and levamisole allowed
• No concurrent chemotherapy NOTE: *Patients must have continued therapy until progressive disease was noted

Endocrine therapy

• Not specified

Radiotherapy

• More than 30 days since prior radiotherapy
• No prior radiotherapy to index lesions
• No concurrent radiotherapy

Surgery

• Not specified

Other

• More than 30 days since any other prior experimental agents
• More than 30 days since any other prior antitumor therapy
• No prior epidermal growth factor receptor (EGFR)-targeting agents
• No other concurrent investigational agents
• No other concurrent EGFR-targeting agents

California
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-7187,  United States; Recruiting

Study chairs or principal investigators

Joel Randolph Hecht, MD,  Principal Investigator,  Jonsson Comprehensive Cancer Center   

Study ID Numbers:  CDR0000373839; UCLA-0402029-01; AMGEN-2003167
Record last reviewed:  June 2004
Record first received:  July 8, 2004
ClinicalTrials.gov Identifier:  NCT00087243
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-08