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.

Condition	Treatment or Intervention	Phase
recurrent colon cancer Stage IV rectal cancer recurrent rectal cancer stage IV colon cancer	Drug: carmustine  Drug: fluorouracil  Drug: monoclonal antibody A33  Drug: streptozocin  Drug: vincristine	Phase I

Further Study Details: 

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.

PROTOCOL 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.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--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

--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

--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

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

Study chairs or principal investigators

Sydney Welt,  Study Chair,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000066597; MSKCC-98056; NCI-H98-0022
Record last reviewed:  August 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003543
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08