Monoclonal Antibody Therapy in Treating Patients With Advanced Colorectal Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase I Study of Humanized 3S193 (Anti-Lewis-Y) Antibody in Patients With Advanced Colorectal Carcinoma

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Biological: monoclonal antibody hu3S193


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hu3S193 10 mg/m2<br>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. | Biological: monoclonal antibody hu3S193<br> <br> |
| Experimental: Hu3S193 25 mg/m2<br>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. | Biological: monoclonal antibody hu3S193<br> <br> |
| Experimental: Hu3S193 50 mg/m2<br>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. | Biological: monoclonal antibody hu3S193<br> <br> |
| Experimental: Hu3S193 100 mg/m2<br>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. | Biological: monoclonal antibody hu3S193<br> <br> |
| Experimental: Hu3S193 200 mg/m2<br>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. | Biological: monoclonal antibody hu3S193<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Dose-limiting Toxicities (DLTs) | 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. | up to 10 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Tumor Responses | 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. | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV colon cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer