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

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

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

Study Overview

• Status: Completed
• Conditions: Stage IV Colon Cancer; Stage IV Rectal Cancer; Recurrent Colon Cancer; Recurrent Rectal Cancer; Adenocarcinoma of the Rectum; Adenocarcinoma of the Colon
• Intervention / Treatment: Drug: iodine I 131 monoclonal antibody CC49-deltaCH2

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (monoclonal antibody); 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; Given IV; Other Names: 131I-HuCC49-deltaCH2; 131I-MOAB CC49-deltaCH2

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Immune response	Up to 54 weeks

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Ruby Meredith, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start: October 1, 2001
• Primary Completion (Actual): July 1, 2005

Study Registration Dates

• First Submitted: September 13, 2001
• First Submitted That Met QC Criteria: June 19, 2003
• First Posted (Estimate): June 20, 2003

Study Record Updates

• Last Update Posted (Estimate): January 25, 2013
• Last Update Submitted That Met QC Criteria: January 24, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Disease Attributes; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Recurrence; Adenocarcinoma; Rectal Neoplasms; Colonic Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Antibodies, Monoclonal
• Other Study ID Numbers: NCI-2012-02406; UAB 9846; CDR0000068877 (Registry Identifier: PDQ (Physician Data Query))