Tanespimycin in Treating Patients With Stage III-IV Melanoma

Study Overview
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Brief Summary
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This phase II trial is studying how well tanespimycin works in treating patients with stage III or stage IV melanoma. Antitumor antibiotics such as tanespimycin may stop the growth of melanoma by stopping blood flow to the tumor.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine if treatment with 17-AAG results in measurable anti-tumor effects and calculate the proportion of clinical responses. II. Test the hypothesis that treatment with 17-AAG can disrupt the MAPK pathway by depleting intra-tumor stores of RAF kinases and/or downstream proteins such as phospho-ERK, CDK4 and cyclin D1. III. Determine if either of these effects correlates with the presence of mutated BRAF within the melanoma tumor. OUTLINE: This is a multicenter study. Patients are stratified according to presence of BRAF mutation in tumor (yes vs no). Patients receive tanespimycin IV over 1-6 hours once weekly for 6 weeks. Courses repeat every 56 days in the absence of disease progression or unacceptable toxicity.

Official Title
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Phase II Trial of 17-N-allylamino-17-demethoxy Geldanamycin (17-AAG, NSC #330507) Diluted in EPL Diluent (NSC #704057) in Metastatic Melanoma Patients

Conditions
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Recurrent Melanoma, Stage III Melanoma, Stage IV Melanoma

Intervention / Treatment
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* Drug: tanespimycin
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed melanoma Stage III or IV disease No primary melanoma of the choroid or mucosa Measurable disease At least 1 unidimensionally measurable lesion >= 20 mm by conventional techniques OR >= 10 mm by spiral CT scan Tumor amenable to biopsy (for the first 10 patients in each stratum only) Patients must have measurable disease in addition to the tumor(s) to be biopsied No brain or epidural metastases Completely resected solitary brain metastases allowed provided patient has been free of CNS metastases for >= 6 months Performance status - Karnofsky 60-100% Performance status - ECOG 0-2 More than 3 months Absolute neutrophil count >= 1,500/mm^3 Platelet count >= 100,000/mm^3 WBC >= 3,000/mm^3 AST and ALT =< 2.5 times upper limit of normal Creatinine normal No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia No history of myocardial infarction No history of prolonged QTc interval No active ischemic heart disease within the past 12 months No uncontrolled dysrhythmia or dysrhythmias requiring medication No congenital prolonged QT syndrome No left bundle branch block Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No prior allergic reaction attributed to compounds of similar chemical or biological composition to 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) No prior serious allergic reaction to eggs No other uncontrolled illness No active or ongoing infection requiring systemic antimicrobial treatment No psychiatric illness or social situation that would preclude study compliance No more than 1 prior chemotherapy regimen for metastatic melanoma Prior vaccines, cytokines, or interferon alfa is not considered prior therapy unless administered with a chemotherapy drug More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered Prior radiotherapy dose =< 3,000 cGy to fields including substantial marrow More than 4 weeks since prior radiotherapy and recovered No prior radiotherapy field that included the heart (e.g., mantle) No concurrent combination antiretroviral therapy for HIV-positive patients No concurrent medications that may prolong the QTc interval No other concurrent anticancer therapy No other concurrent investigational agents No concurrent treatment with any of the following medications or herbal remedies: Inhibitors of CYP3A4: Fluconazole Itraconazole Ketoconazole Macrolide antibiotics (azithromycin, clarithromycin, erythromycin, or troleandomycin) Midazolam Nifedipine Verapamil Diltiazem Terfenadine Cyclosporine Cisapride Inducers of CYP3A4: Carbamazepine Phenobarbital Phenytoin Rifampin Herbal extracts and tinctures with CYP3A4 inhibitory activity: Hydrastis canadensis (goldenseal) Hypericum perforatum (St. John's wort) Uncaria tomentosa (cat's claw) Echinacea angustifolia roots Trifolium pratense (wild cherry) Matricaria chamomilla (chamomile) Glycyrrhiza glabra (licorice) Dillapiol Hypericin Naringin No other concurrent herbal extracts

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: Treatment (tanespimycin)<br>Patients receive tanespimycin IV over 1-6 hours once weekly for 6 weeks. Courses repeat every 56 days in the absence of disease progression or unacceptable toxicity. | Drug: tanespimycin<br>* Given IV<br>* Other names: 17-AAG;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate (complete and partial response) |  | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with stable disease |  | At 1 year | 
| Frequency of toxicities |  | Up to 3 years |