Monoclonal Antibody Therapy Plus Combination Chemotherapy in Treating Patients With Advanced Colorectal Cancer

Phase I Study of Combination Immunochemotherapy in Patients With Advanced Colorectal Carcinoma

RATIONALE: Monoclonal antibodies can find and locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and combining chemotherapy with monoclonal antibody therapy may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of monoclonal antibody therapy plus combination chemotherapy in treating patients with advanced colorectal cancer.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: fluorouracil; Drug: vincristine sulfate; Drug: carmustine; Drug: streptozocin; Biological: monoclonal antibody A33

Detailed Description

OBJECTIVES: I. Define toxicity and the maximum tolerated dose of humanized monoclonal antibody A33 (MOAB A33) when combined with carmustine, fluorouracil, vincristine, and streptozocin in patients with advanced colorectal cancer. II. Determine the effect of chemotherapy on human antihuman antibody response and on the pharmacokinetics of humanized MOAB A33 in these patients. III. Define the humanized MOAB A33 dose for a phase II study.

OUTLINE: This is a dose escalation study of humanized monoclonal antibody A33 (MOAB A33). Patients receive humanized MOAB A33 IV once a week for 14 weeks. Chemotherapy begins on day 29 and consists of carmustine IV on days 29-33, fluorouracil IV on days 29-33 and 64-68, vincristine IV on days 29 and 64, and streptozocin IV every 7 days, beginning on day 29, for 10 doses. Courses repeat every 14 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of humanized MOAB A33. The maximum tolerated dose is defined as the dose at which no more than 2 of 6 patients experience dose limiting toxicity.

PROJECTED ACCRUAL: There will be 3-18 patients accrued into this study over 2-9 months.

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS: Histologically confirmed unresectable stage IV colon or rectal cancer that has failed conventional chemotherapy for advanced disease or refused other treatment Measurable disease No liver involvement of greater than 50% No clinical evidence of CNS tumor involvement

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 80-100% Life expectancy: At least 14 weeks Hematopoietic: WBC at least 3,5000/mm3 Platelet count at least 150,000/mm3 Hepatic: Bilirubin no greater than 1.0 mg/dL Renal: Creatinine no greater than 1.5 mg/dL Cardiovascular: No clinically significant cardiac disease (New York Heart Association class III/IV heart disease) Other: No positive human antimouse antibody titer No serious infection requiring treatment with antibiotics No other serious illness Not pregnant or nursing Effective contraception required of all fertile patients

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior mouse monoclonal antibody or antibody fragment, or chimeric or humanized antibody At least 4 weeks since prior immunotherapy Chemotherapy: No prior carmustine, fluorouracil, vincristine, and streptozocin At least 4 weeks since prior chemotherapy Endocrine therapy: Not specified Radiotherapy: At least 4 weeks since prior radiotherapy Surgery: Not specified

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: June 1, 1998
• Primary Completion (ACTUAL): August 1, 2002
• Study Completion (ACTUAL): August 1, 2002

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: August 13, 2004
• First Posted (ESTIMATE): August 16, 2004

Study Record Updates

• Last Update Posted (ESTIMATE): June 27, 2013
• Last Update Submitted That Met QC Criteria: June 25, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: stage IV rectal cancer; stage IV colon cancer; recurrent colon cancer; recurrent rectal cancer
• 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; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Phytogenic; Antibiotics, Antineoplastic; Antibodies; Fluorouracil; Antibodies, Monoclonal; Vincristine; Carmustine; Streptozocin
• Other Study ID Numbers: 98-056; CDR0000066597 (REGISTRY: PDQ (Physician Data Query)); NCI-H98-0022