Tanespimycin in Treating Patients With Stage III-IV Melanoma

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00087386
First received: July 8, 2004
Last updated: April 9, 2013
Last verified: April 2013
  Purpose

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 Intervention Phase
Recurrent Melanoma
Stage III Melanoma
Stage IV Melanoma
Drug: tanespimycin
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response rate (complete and partial response) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of patients with stable disease [ Time Frame: At 1 year ] [ Designated as safety issue: No ]
  • Frequency of toxicities [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 50
Study Start Date: June 2004
Primary Completion Date: February 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 17-AAG
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00087386

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Investigators
Principal Investigator: Paul Chapman Memorial Sloan-Kettering Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00087386     History of Changes
Other Study ID Numbers: NCI-2012-01453, 04-056, NCI-6480, CDR0000374980, MSKCC-04056, N01CM62206
Study First Received: July 8, 2004
Last Updated: April 9, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on April 17, 2014