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Tanespimycin in Treating Patients With Stage III-IV Melanoma

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Terminated
CT.gov ID
NCT00087386
Collaborator
(none)
50
Enrollment
1
Location
1
Arm

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

PRIMARY OBJECTIVES:

  1. Determine if treatment with 17-AAG results in measurable anti-tumor effects and calculate the proportion of clinical responses.

  2. 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.

  3. 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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
50 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase II Trial of 17-N-allylamino-17-demethoxy Geldanamycin (17-AAG, NSC #330507) Diluted in EPL Diluent (NSC #704057) in Metastatic Melanoma Patients
Study Start Date :
Jun 1, 2004
Actual Primary Completion Date :
Feb 1, 2007

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment (tanespimycin)

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
Given IV
Other Names:
  • 17-AAG

    • Other: laboratory biomarker analysis
    Correlative studies

    Outcome Measures

    Primary Outcome Measures

    1. Response rate (complete and partial response) [Up to 3 years]

    Secondary Outcome Measures

    1. Proportion of patients with stable disease [At 1 year]

    2. Frequency of toxicities [Up to 3 years]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Memorial Sloan-Kettering Cancer Center New York New York United States 10065

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Paul Chapman, Memorial Sloan Kettering Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT00087386
    Other Study ID Numbers:
    • NCI-2012-01453
    • 04-056
    • NCI-6480
    • CDR0000374980
    • MSKCC-04056
    • N01CM62206
    First Posted:
    Jul 12, 2004
    Last Update Posted:
    Apr 10, 2013
    Last Verified:
    Apr 1, 2013
    Additional relevant MeSH terms:
    Melanoma

    Study Results

    No Results Posted as of Apr 10, 2013