- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00006046
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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New York
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New York, New York, United States, 10021
- Memorial Sloan-Kettering Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Hu3S193 10 mg/m2
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.
|
|
Experimental: Hu3S193 25 mg/m2
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.
|
|
Experimental: Hu3S193 50 mg/m2
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.
|
|
Experimental: Hu3S193 100 mg/m2
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.
|
|
Experimental: Hu3S193 200 mg/m2
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Patients With Dose-limiting Toxicities (DLTs)
Time Frame: 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.
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up to 10 weeks.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Patients With Tumor Responses
Time Frame: 8 weeks
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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.
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8 weeks
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Collaborators and Investigators
Investigators
- Study Chair: Sydney Welt, MD, Memorial Sloan Kettering Cancer Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Colorectal Neoplasms
- Physiological Effects of Drugs
- Immunologic Factors
- Antibodies
- Antibodies, Monoclonal
Other Study ID Numbers
- CDR0000068062
- MSKCC-00005 (Other Identifier: Memorial Sloan-Kettering Cancer Center)
- LUD1999-007 (Other Identifier: Ludwig Institute for Cancer Research)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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