O6-benzylguanine and Carmustine in Treating Patients With Unresectable Locally Recurrent or Metastatic Melanoma

Study Overview
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Brief Summary
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Phase II trial to study the effectiveness of O6-benzylguanine and carmustine in treating patients who have unresectable locally recurrent or metastatic melanoma. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than once chemotherapy drug may kill more tumor cells.

Detailed Description
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OBJECTIVES: I. Determine the objective clinical response rate and duration of response in patients with unresectable locally recurrent or metastatic melanoma treated with O6-benzylguanine and carmustine. II. Compare the toxicities of this regimen in patients with no prior chemotherapy vs prior chemotherapy failure. III. Correlate clinical response to this regimen in these patients with O6-alkylguanine DNA alkyltransferase (AGT) depletion and baseline AGT in peripheral blood mononuclear cells and tumor tissue. OUTLINE: This is a multicenter study. Patients are stratified according to prior chemotherapy (chemotherapy failure vs chemotherapy naive). Patients receive O6-benzylguanine IV over 1 hour, followed 1 hour later by carmustine IV over 1 hour on day 1. Treatment continues every 6 weeks for a minimum of 2 courses in the absence of disease progression or unacceptable toxicity. Patients with disease progression are followed every 6 months. All other patients are followed every 3 months for 1 year.

Official Title
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A Phase II Trial of O6-Benzylguanine (NSC 637037) and BCNU (Carmustine) in Patients With Metatstatic Melanoma

Conditions
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Melanoma (Skin)

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: Histologically proven unresectable locally recurrent or metastatic melanoma Chemotherapy naive with no more than 2 prior immunotherapy regimens (including cytokines, vaccines, or adjuvant interferon) OR Prior chemotherapy failure with no more than 2 prior immunotherapy regimens (including adjuvant interferon) and no more than 1 prior chemotherapy regimen (which may include carmustine) not including antiangiogenesis therapy Measurable disease At least 20 mm in at least 1 dimension by conventional technique OR at least 10 mm in at least 1 dimension by spiral CT scan No disease confined only to the CNS No uncontrolled symptomatic brain metastases regardless of other disease sites PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: At least 12 weeks Hematopoietic: WBC at least 3,000/mm^3 Absolute neutrophil count at least 1,200/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Bilirubin no greater than 1.5 mg/dL AST and/or ALT no greater than 3 times upper limit of normal PT normal Renal: Creatinine no greater than 1.5 mg/dL OR Creatinine clearance greater than 60 mL/min Pulmonary: DLCO at least 70% predicted Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No concurrent significant psychiatric or medical illness, including active infections, that would interfere with study therapy or increase risk No other malignancy within the past 5 years except curatively treated nonmelanomatous skin cancer, carcinoma in situ of the cervix, or superficial bladder cancer PRIOR CONCURRENT THERAPY: Chemotherapy: At least 4 weeks since prior systemic chemotherapy (at least 6 weeks since prior carmustine or mitomycin) and recovered No other concurrent chemotherapy or investigational antineoplastic drugs Radiotherapy: At least 2 weeks since prior radiotherapy and recovered No concurrent radiotherapy Surgery: At least 3 weeks since prior major surgery and recovered Other: At least 4 weeks since other prior anticancer systemic therapy and recovered

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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive O6-benzylguanine IV over 1 hour, followed 1 hour later by carmustine IV over 1 hour on day 1. Treatment continues every 6 weeks for a minimum of 2 courses in the absence of disease progression or unacceptable toxicity. | Drug: O6-benzylguanine<br> <br> Drug: carmustine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage III melanoma, stage IV melanoma, recurrent melanoma