SB-715992 in Treating Patients With Metastatic or Recurrent Malignant Melanoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as SB-715992, work in different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: This phase II trial is studying how well SB-715992 works in treating patients with metastatic or recurrent malignant melanoma.

Detailed Description
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OBJECTIVES: Determine the efficacy of SB-715992, in terms of response rate, in patients with previously untreated metastatic or recurrent malignant melanoma. Determine the toxic effects of this drug in these patients. Determine the early progression rate and response duration in patients treated with this drug. Determine the pharmacokinetics of this drug in these patients. Correlate pharmacokinetics with safety and efficacy endpoints of this drug in these patients. Correlate β-tubulin and kinesin spindle protein expression in tumor tissue with clinical outcomes in patients treated with this drug. OUTLINE: This is a nonrandomized, multicenter study. Patients receive SB-715992 IV over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients are followed at 4 weeks after completion of protocol therapy. Patients with ongoing complete response, partial response, or stable disease are followed every 3 months thereafter until relapse. PROJECTED ACCRUAL: A total of 15-25 patients will be accrued for this study within 12-14 months.

Official Title
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A Phase II Study of SB-715992 (NSC 727990) in Previously Untreated Patients With Metastatic or Recurrent Malignant Melanoma

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Drug: ispinesib


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed malignant melanoma Previously untreated metastatic or recurrent disease Considered incurable by standard therapies Measurable disease At least one unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan Bone metastases are not considered measurable disease Outside any previously irradiated area Patients whose sole site of measurable disease is in a previously irradiated area are ineligible unless there is evidence of progression or new lesions documented in the irradiated field No known CNS metastases CT scans or MRI are not required to rule out CNS metastases unless patient exhibits neurological signs or symptoms Patients with a prior solitary brain metastasis surgically resected with no evidence of residual disease are eligible provided CT scan or MRI confirms no evidence of disease within the past 28 days Archival paraffin tumor specimen available PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy At least 12 weeks Hematopoietic Absolute granulocyte count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic Bilirubin normal AST and ALT ≤ 2.5 times upper limit of normal (ULN) Renal Creatinine ≤ 1.5 times ULN Cardiovascular No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other malignancy except adequately treated nonmelanoma skin cancer, curatively treated carcinoma in situ of the cervix, or other curatively treated solid tumors with no evidence of disease for ≥ 5 years No other uncontrolled illness No ongoing or active infection No psychiatric illness or social situation that would preclude study participation No history of allergic reactions attributed to compounds of similar chemical or biological composition to SB-715992 PRIOR CONCURRENT THERAPY: Biologic therapy At least 3 months since prior adjuvant immunotherapy No prior immunotherapy for metastatic or recurrent disease Chemotherapy No prior chemotherapy, including regional therapy Endocrine therapy Not specified Radiotherapy See Disease Characteristics At least 4 weeks since prior radiotherapy except for low-dose, non-myelosuppressive radiotherapy Surgery See Disease Characteristics At least 4 weeks since prior major surgery Other More than 28 days since prior investigational agents More than 14 days since prior and no concurrent use of any of the following CYP3A4 inhibitors or inducers: Clarithromycin Erythromycin Troleandomycin Itraconazole Ketoconazole Fluconazole (≤ 200 mg/day allowed) Voriconazole Nefazodone Fluvoxamine Verapamil Diltiazem Grapefruit juice Bitter orange Phenytoin Carbamazepine Phenobarbital Oxcarbazepine Rifampin Rifabutin Rifapentine Hypericum perforatum (St. John's wort) Modafinil At least 6 months since prior and no concurrent amiodarone No concurrent antiretroviral therapy for HIV-positive patients No other concurrent anticancer treatment No other concurrent investigational therapies

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: ispinesib|SB-715992 will be given as a 1 hour intravenous infusion in a dose of 18 mg/m2 once every 3 weeks.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity |  | 2 years | 
| Pharmacokinetics at day 1 of course 1 (day 1 of course 2 if dose is changed) |  | 2 years | 
| Molecular correlates on archival tissue, fresh tumor tissue, and peripheral blood mononuclear cells (PVMCs) |  | 2 years | 

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