Phase I Study of the Hsp90 Inhibitor, AT13387, in Adults With Refractory Solid Tumors

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed solid tumor malignancy

- Metastatic or unresectable disease for which no standard curative measures exist
OR failed ≥ 1 line of standard therapy

- Measurable or evaluable disease

- Archived tumor tissue must be HER2/neu ≥ 1+ by IHC (expansion phase)

- Disease amenable to biopsy

- No known brain metastases or carcinomatous meningitis

- Brain metastatic disease that has remained stable for ≥ 2 months after
treatment, without steroids or anti-seizure medications, allowed at the
discretion of the principal investigator

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2

- Life expectancy > 3 months

- ANC ≥ 1,500/μL

- Platelet count ≥ 100,000/μL

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST and ALT ≤ 2.5 times ULN

- Creatinine < 1.5 times ULN OR creatinine clearance ≥ 60 mL/min

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must agree to use adequate contraception (hormonal, barrier method
of birth control, or abstinence) prior to, during, and for 2 months after completion
of study

- Willingness to undergo pre- and post-treatment biopsies (expansion phase)

- No clinically significant intercurrent illnesses including, but not limited to, any
of the following:

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Uncontrolled cardiac arrhythmia

- Psychiatric illness and/or social situations that would limit compliance with
study requirements

- QTc > 450 msec (for men) or QTc > 470 msec (for women)

PRIOR CONCURRENT THERAPY:

- At least 4 weeks since prior chemotherapy, radiotherapy, or biologic therapy (6 weeks
for nitrosoureas or mitomycin C)

- At least 2 weeks since any prior drug in an exploratory IND/phase 0 study

- Recovered from prior toxicity or adverse events

- Concurrent bisphosphonates for any cancer allowed

- No concurrent combination antiretroviral therapy for HIV-positive patients