RATIONALE: Monoclonal antibodies can locate tumor cells and deliver tumor-killing substances, such as radioactive iodine, to them without harming normal cells.

PURPOSE: Phase I trial to study the effectiveness of radiolabeled monoclonal antibody 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: iodine I 131 monoclonal antibody A33	Phase I

Further Study Details: 

OBJECTIVES: I. Define the toxicity and determine the maximum tolerated dose of iodine I 131 humanized monoclonal antibody A33 (131I-huAb A33) in patients with advanced colorectal cancer.

II. Describe pharmacokinetics and biodistribution of 131I-huAb A33 by external imaging in these patients.

III. Determine the effect of human antihuman antibody response on pharmacokinetics and targeting of 131I-huAb A33 in this patient population.

IV. Determine whether the dose planning methodology used here can adequately and safely be applied to routine radioimmunotherapy planning.

PROTOCOL OUTLINE: Patients receive iodine I 131 humanized monoclonal antibody A33 (131I-huAb A33) by IV infusion over 20 minutes every 6-8 days for up to 8 weeks (depending on dosage). Patients receive a minimum of 6 weeks of treatments. In the absence of disease progression or unacceptable toxicity, patients are retreated no sooner than 6 weeks after the previous course.

Cohorts of 3-6 patients receive escalating doses of 131I-huAb A33 to determine the maximum tolerated dose (MTD). The MTD is defined as the highest dose at which no more than 2 of 6 patients experience dose limiting toxicity.

Patients are followed for 6 weeks after the last treatment.

PROJECTED ACCRUAL: There will be 3-24 patients accrued into this study over 16 months.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed advanced colorectal cancer; Must have unresectable (Stage IV) disease or have failed or refused conventional chemotherapy
• Measurable disease by conventional imaging methods
• Liver involvement no greater than 50%
• No CNS involvement
• Not positive for human antimouse antibody titer

--Prior/Concurrent Therapy--

• Biologic therapy: No prior mouse monoclonal antibody or antibody fragment, chimeric or humanized antibody, or constructs derived from antibodies; At least 4 weeks since prior immunotherapy
• Chemotherapy: No prior mitomycin/radiotherapy combination; At least 4 weeks since prior chemotherapy
• Endocrine therapy: No concurrent steroids or other antiinflammatory agents
• Radiotherapy: No prior radiotherapy/mitomycin combination
• Surgery: Not specified

--Patient Characteristics--

• Age: 18 and over
• Performance status: Karnofsky 80-100%
• Life expectancy: At least 12 weeks
• Hematopoietic: WBC at least 3,500/mm3; Platelet count at least 150,000/mm3; Prothrombin time less than 1.3 times control
• Hepatic: Bilirubin no greater than 1 mg/dL
• Renal: Creatinine no greater than 1.5 mg/dL
• Cardiovascular: No significant cardiac disease (New York Heart Association class II/IV heart disease)
• Other: 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:  CDR0000066342; MSKCC-98011; NCI-H98-0017
Record last reviewed:  August 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003360
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08