Monoclonal Antibody Therapy in Treating Patients With Advanced Colorectal Cancer

Phase I Study of Humanized 3S193 (Anti-Lewis-Y) Antibody in Patients With Advanced 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 I trial to study the effectiveness of monoclonal antibody therapy in treating patients who have advanced colorectal cancer.

OBJECTIVES:

• Determine the toxicity, maximum tolerated dose, and pharmacokinetics of monoclonal antibody hu3S193 in patients with advanced colorectal carcinoma.
• Determine the immune response in these patients treated with this regimen.

OUTLINE: This is a dose escalation study.

Patients receive monoclonal antibody hu3S193 (mAb hu3S193) IV over 30 minutes to 4 hours weekly for 8 weeks followed by 2 weeks of rest. Patients with stable or responding disease at week 10 receive maintenance mAb hu3S193 weekly. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of mAb hu3S193 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 patients experience dose limiting toxicities.

Inclusion Criteria:

• Histologically proven stage IV colorectal carcinoma.
• Failed or refused conventional chemotherapy.
• Lewis Y antigen present on more than 50% of tumor cells.
• Measurable or evaluable disease.
• No central nervous system (CNS) tumor involvement.
• Karnofsky 80-100%.
• Life expectancy: At least 6 weeks.
• Granulocyte count greater than 1,500/mm^3.
• Platelet count greater than 100,000/mm^3.
• Bilirubin no greater than 1.0 mg/dL.
• Prothrombin time less than 3 times upper limit of normal.
• Creatinine no greater than 1.4 mg/dL.
• Female patients of childbearing age and male patients must be asked to use effective contraception during the study.
• At least 4 weeks since other prior immunotherapy. Exclusion Criteria
• New York Heart Association class III or IV heart disease.
• Serious infection requiring antibiotics or other serious illness.
• Pregnancy or nursing.
• History of bleeding gastric ulcers or pancreatitis.
• Diabetes mellitus requiring insulin.
• Human antimouse antibodies (HAMA).
• No prior mouse monoclonal antibody or antibody fragments.
• Illness requiring the use of steroids or other anti-inflammatory agents.
• Positive anti-hu3S193 antibody (HAHA) titer.