Radiolabeled Monoclonal Antibody Therapy in Treating Patients With Recurrent or Persistent Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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Phase I trial to study the effectiveness of radiolabeled monoclonal antibody therapy in treating patients who have recurrent or persistent metastatic colorectal cancer. Radiolabeled monoclonal antibodies can locate tumor cells and deliver tumor-killing substances to them without harming normal cells. Radiolabeled monoclonal antibody therapy may be effective treatment for colorectal cancer

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the maximum tolerated dose of iodine I 131 monoclonal antibody CC49-deltaCH2 (deleted CH2 region) in patients with colorectal cancer. II. Determine the toxic effects, plasma pharmacokinetics, whole body biodistribution, and conjugate stability of this drug in these patients. III. Determine the ability of this drug to localize to tumor sites in these patients. IV. Determine the immune response in patients treated with this drug. OUTLINE: This is a dose-escalation study. Patients receive a tracer dose of iodine I 131 monoclonal antibody CC49-deltaCH2 IV on day 1 and a therapy dose over 30 minutes on day 8. Cohorts of 3-5 patients receive escalating doses of iodine I 131 monoclonal antibody CC49-deltaCH2 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 3 of 5 patients experience grade 3 or greater toxicity while 0-2 of 5 patients experience reversible grade 4 hematologic toxicity. Patients are followed weekly for a minimum of 7 weeks and then every 6 weeks until disease progression.

Official Title
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Phase I Trial of 131I-HuCC49^CH2 for Colon Cancer

Conditions
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Adenocarcinoma of the Colon, Adenocarcinoma of the Rectum, Recurrent Colon Cancer, Recurrent Rectal Cancer, Stage IV Colon Cancer, Stage IV Rectal Cancer

Intervention / Treatment
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* Drug: iodine I 131 monoclonal antibody CC49-deltaCH2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed metastatic adenocarcinoma of the colon or rectum Not amenable to surgical resection Recurrent or persistent disease after standard surgery, radiotherapy, and chemotherapy, including fluorouracil and irinotecan TAG-72 positive Performance status - ECOG 0-2 WBC greater than 3,500/mm^3 Platelet count greater than 125,000/mm^3 Hemoglobin greater than 10 g/dL No nucleated RBC or significant teardrop RBC morphology Bilirubin less than 1.5 mg/dL SGOT/SGPT less than 4 times normal Hepatitis B surface antigen negative Creatinine less than 2.0 mg/dL HIV negative No other malignancy within the past 5 years except basal cell skin cancer No allergy to iodine No detectable antibody to monoclonal antibody CC49 Not pregnant or nursing Fertile patients must use effective contraception At least 3 weeks since prior immunotherapy and recovered No prior bone marrow or stem cell transplantation No other concurrent immunotherapy See Disease Characteristics At least 3 weeks since prior chemotherapy and recovered No concurrent chemotherapy See Disease Characteristics At least 3 weeks since prior radiotherapy and recovered No prior radiotherapy to more than 25% of red marrow No concurrent radiotherapy See Disease Characteristics At least 3 weeks since prior surgery and recovered

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (monoclonal antibody)<br>Patients receive a tracer dose of iodine I 131 monoclonal antibody CC49-deltaCH2 IV on day 1 and a therapy dose over 30 minutes on day 8. Cohorts of 3-5 patients receive escalating doses of iodine I 131 monoclonal antibody CC49-deltaCH2 until the MTD is determined. The MTD is defined as the dose at which 3 of 5 patients experience grade 3 or greater toxicity while 0-2 of 5 patients experience reversible grade 4 hematologic toxicity. | Drug: iodine I 131 monoclonal antibody CC49-deltaCH2<br>* Given IV<br>* Other names: 131I-MOAB CC49-deltaCH2;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose of 131I-HuCC49^CH2 based on dose-limiting toxicities |  | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune response |  | Up to 54 weeks |