Combination Chemotherapy in Treating Patients With Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: O6-benzylguanine
* Drug: carmustine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 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

| Intervention/Treatment |
| --- |
|Drug: O6-benzylguanine|Patients receive O6-benzylguanine (BG) IV over 1 hour. Treatment continues every 6 weeks in the absence of disease progression or unacceptable toxicity.|
|Drug: carmustine|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.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV colon cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer