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.
- 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.
PROJECTED ACCRUAL: A total of 18-30 patients will be accrued for this study.
- 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 CNS tumor involvement
- 18 and over
- Karnofsky 80-100%
- 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 1.3 times control
- Creatinine no greater than 1.4 mg/dL
- No New York Heart Association class III or IV heart disease
- No serious infection requiring antibiotics or other serious illness
- Not pregnant or nursing
- No history of bleeding gastric ulcers or pancreatitis
- No diabetes mellitus requiring insulin
- Human antimouse antibody (HAMA) negative
PRIOR CONCURRENT THERAPY:
- No prior mouse monoclonal antibody or antibody fragments
- At least 4 weeks since other prior immunotherapy
- See Disease Characteristics
- At least 4 weeks since prior chemotherapy
- No concurrent steroids or other antiinflammatory agents
- At least 4 weeks since prior radiotherapy
- Not specified