Combination Chemotherapy in Treating Patients With Metastatic Colorectal Cancer

Phase II Trial of O6Benzylguanine and BCNU in Patients With Colon and Rectal Carcinoma

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy in treating patients who have metastatic colorectal cancer.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: O6-benzylguanine; Drug: carmustine

Detailed Description

OBJECTIVES:

• Determine the response rate of patients with metastatic colorectal carcinoma treated with O6-benzylguanine and carmustine.
• Evaluate tumor tissue biochemical and immunohistochemical predictors of response in patients treated with this regimen.
• Correlate carcinoembryonic antigen levels in the peripheral blood with response in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive O6-benzylguanine (BG) IV over 1 hour and carmustine IV over 1 hour (beginning 1 hour after completion of BG infusion) on day 1. Treatment continues every 6 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 19-36 patients will be accrued for this study within 1.7-3 years.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106-5065
      • Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive 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:

• Diagnosis of metastatic colorectal carcinoma
• Bidimensionally measurable disease

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

• WBC at least 4,000/mm^3
• Granulocyte count at least 1,500/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin greater than 8 g/dL

Hepatic:

• Bilirubin no greater than 1.2 mg/dL
• AST and ALT less than 2.5 times upper limit of normal (ULN)
• PT no greater than ULN (not on anticoagulation therapy)

Renal:

• Creatinine no greater than 1.5 mg/dL
• Creatine clearance greater than 60 mL/min

Pulmonary:

• DLCO at least 60%

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 2 months after study
• No other concurrent active malignancies
• Prior malignancies presumed to be cured allowed
• No other concurrent uncontrolled severe medical problem that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 6 months since prior adjuvant chemotherapy without disease recurrence
• No more than 1 prior chemotherapy regimen for metastatic disease

Endocrine therapy:

• Not specified

Radiotherapy:

• Prior adjuvant radiotherapy allowed
• No prior radiotherapy to more than 25% of total bone marrow

Surgery:

• Not specified

Other:

• No other prior therapy for advanced disease

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Determine the response rate of patients with metastatic colorectal carcinoma treated with O6-benzylguanine and carmustine.	Treatment continues every 6 weeks in the absence of disease progression or unacceptable toxicity.

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Smitha Krishnamurthi, MD, Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: June 1, 2000
• Primary Completion (Actual): November 1, 2003
• Study Completion (Actual): November 1, 2003

Study Registration Dates

• First Submitted: July 5, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): June 10, 2010
• Last Update Submitted That Met QC Criteria: June 9, 2010
• Last Verified: June 1, 2010

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; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Carmustine; O(6)-benzylguanine
• Other Study ID Numbers: CWRU1298; P30CA043703 (U.S. NIH Grant/Contract); U01CA063200 (U.S. NIH Grant/Contract); CWRU-1298; NCI-89