Monoclonal Antibody Therapy in Treating Patients With Advanced Colorectal Cancer

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Primary Purpose

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

monoclonal antibody hu3S193

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring stage IV colon cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Memorial Sloan-Kettering Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Arm Label

Hu3S193 10 mg/m2

Hu3S193 25 mg/m2

Hu3S193 50 mg/m2

Hu3S193 100 mg/m2

Hu3S193 200 mg/m2

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT00006046

First Posted

July 5, 2000

Last Updated

October 2, 2023

Sponsor

Ludwig Institute for Cancer Research

1. Study Identification

Unique Protocol Identification Number

NCT00006046

Brief Title

Monoclonal Antibody Therapy in Treating Patients With Advanced Colorectal Cancer

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Terminated

Why Stopped

poor recruitment

Study Start Date

July 12, 2000 (Actual)

Primary Completion Date

October 5, 2001 (Actual)

Study Completion Date

September 24, 2002 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Ludwig Institute for Cancer Research

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colorectal Cancer

Keywords

stage IV colon cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

7 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Hu3S193 10 mg/m2

Arm Type

Experimental

Arm Description

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.

Arm Title

Hu3S193 25 mg/m2

Arm Type

Experimental

Arm Description

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.

Arm Title

Hu3S193 50 mg/m2

Arm Type

Experimental

Arm Description

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.

Arm Title

Hu3S193 100 mg/m2

Arm Type

Experimental

Arm Description

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.

Arm Title

Hu3S193 200 mg/m2

Arm Type

Experimental

Arm Description

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.

Intervention Type

Biological

Intervention Name(s)

monoclonal antibody hu3S193

Primary Outcome Measure Information:

Title

Number of Patients With Dose-limiting Toxicities (DLTs)

Description

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.

Time Frame

up to 10 weeks.

Secondary Outcome Measure Information:

Title

Number of Patients With Tumor Responses

Description

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.

Time Frame

8 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sydney Welt, MD

Organizational Affiliation

Memorial Sloan Kettering Cancer Center

Official's Role

Study Chair

Facility Information:

Facility Name

Memorial Sloan-Kettering Cancer Center

City

New York

State/Province

New York

ZIP/Postal Code

10021

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

No

Colorectal Cancer

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial