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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

Phase 2
18 Years
Not Enrolling
Recurrent Melanoma, Stage III Melanoma, Stage IV Melanoma

Thank you

Trial Information

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


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.

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

- 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

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response rate (complete and partial response)

Outcome Time Frame:

Up to 3 years

Safety Issue:


Principal Investigator

Paul Chapman

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

June 2004

Completion Date:

Related Keywords:

  • Recurrent Melanoma
  • Stage III Melanoma
  • Stage IV Melanoma
  • Melanoma



Memorial Sloan-Kettering Cancer Center New York, New York  10021