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