Monoclonal Antibody Therapy in Treating Patients With Advanced Colorectal Cancer
- Conditions
- Colorectal Cancer
- Interventions
- Biological: monoclonal antibody hu3S193
- Registration Number
- NCT00006046
- Lead Sponsor
- Ludwig Institute for Cancer Research
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 7
- 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.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Hu3S193 10 mg/m2 monoclonal antibody hu3S193 Hu3S193 was administered weekly for 8 consecutive weeks. The antibody was diluted in physiologic saline containing 5% human serum albumin and infused intravenously at a maximum rate of 100 mg/hour. If patients were stable or responding, they were eligible to receive 8-week maintenance cycles of hu3S193 at 10 mg/m2 starting in week 10 and continuing until progression. Hu3S193 25 mg/m2 monoclonal antibody hu3S193 Hu3S193 was administered weekly for 8 consecutive weeks. The antibody was diluted in physiologic saline containing 5% human serum albumin and infused intravenously at a maximum rate of 100 mg/hour. If patients were stable or responding, they were eligible to receive 8-week maintenance cycles of hu3S193 at 10 mg/m2 starting in week 10 and continuing until progression. Hu3S193 200 mg/m2 monoclonal antibody hu3S193 Hu3S193 was administered weekly for 8 consecutive weeks. The antibody was diluted in physiologic saline containing 5% human serum albumin and infused intravenously at a maximum rate of 100 mg/hour. If patients were stable or responding, they were eligible to receive 8-week maintenance cycles of hu3S193 at 10 mg/m2 starting in week 10 and continuing until progression. Hu3S193 50 mg/m2 monoclonal antibody hu3S193 Hu3S193 was administered weekly for 8 consecutive weeks. The antibody was diluted in physiologic saline containing 5% human serum albumin and infused intravenously at a maximum rate of 100 mg/hour. If patients were stable or responding, they were eligible to receive 8-week maintenance cycles of hu3S193 at 10 mg/m2 starting in week 10 and continuing until progression. Hu3S193 100 mg/m2 monoclonal antibody hu3S193 Hu3S193 was administered weekly for 8 consecutive weeks. The antibody was diluted in physiologic saline containing 5% human serum albumin and infused intravenously at a maximum rate of 100 mg/hour. If patients were stable or responding, they were eligible to receive 8-week maintenance cycles of hu3S193 at 10 mg/m2 starting in week 10 and continuing until progression.
- Primary Outcome Measures
Name Time Method Number of Patients With Dose-limiting Toxicities (DLTs) up to 10 weeks. Toxicity was graded in accordance with the Common Toxicity Scale developed by NCI (1998) where Grade 1 represents the lowest toxicity grade and Grade 5 death. Dose-limiting toxicity (DLT) was defined as Grade 3 and Grade 4 adverse events which were at least possibly related to study treatment.
- Secondary Outcome Measures
Name Time Method Number of Patients With Tumor Responses 8 weeks Complete response (CR); disappearance of all measurable disease lasting a minimum of 4 weeks. Partial Response (PR); 50% or greater decrease in the sum of the products of the perpendicular diameters or all measurable lesions, without development of new lesions or increase in size of any lesion, lasting a minimum of 4 weeks. Progressive disease (PD); Appearance of new lesions or increase by 25% or more in size of any measurable lesion. Stable disease (SD); Not meeting criteria for response or progression.
Trial Locations
- Locations (1)
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States