RATIONALE: Drugs used in chemotherapy, such as 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase I trial is studying the side effects and best dose of 17-DMAG in treating patients with metastatic solid tumors or tumors that cannot be removed by surgery.

OBJECTIVES:

Primary

• Determine the maximum tolerated dose, dose-limiting toxicity, and recommended phase II dose of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) in patients with unresectable or metastatic solid tumors.
• Determine the feasibility, safety, and toxicity profile of this drug in these patients.

Secondary

• Determine the clinical pharmacokinetic profile of this drug in these patients.
• Determine tumor response in patients treated with this drug.
• Determine the biologically effective dose.

OUTLINE: This is an open-label, non-randomized, dose-escalation, multicenter study.

Patients receive 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) IV over 1 hour on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of 17-DMAG until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional 10 patients are treated at the MTD.

After completion of study treatment, patients are followed for 28 days.

PROJECTED ACCRUAL: Approximately 25-35 patients will be accrued for this study within 12-18 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed solid tumor

  • Unresectable or metastatic disease

• Standard curative or palliative measures do not exist OR are no longer effective OR patient refused such measures

• No known brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• More than 12 weeks

Hematopoietic

• Absolute neutrophil count > 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9.0 g/dL

Hepatic

• Bilirubin normal
• ALT and AST ≤ 1.5 times upper limit of normal
• No chronic liver disease
• Hepatitis B or C negative

Renal

• Creatinine normal OR
• Creatinine clearance normal

Cardiovascular

• No symptomatic New York Heart Association class III-IV cardiac disease
• No myocardial infarction within the past year
• No active ischemic heart disease within the past year
• No poorly controlled angina
• No uncontrolled dysrhythmia or dysrhythmias requiring antiarrhythmic drugs
• No transient ischemic attack
• No stroke
• No peripheral vascular disease
• No congenital long QT syndrome
• No history of serious ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row)
• QTc < 450 msec (for men) and 470 msec (for woman)
• LVEF > 40% by MUGA
• No left bundle branch block

Pulmonary

• No symptomatic pulmonary disease requiring medication, including any of the following:

  • Dyspnea with or without exertion
  • Paroxysmal nocturnal dyspnea
  • Oxygen requirement
  • Significant pulmonary disease (e.g., chronic obstructive/restrictive pulmonary disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception 4 weeks before, during, and for 6 months after completion of study treatment
• No known HIV positivity
• No other malignancy within the past 5 years except adequately treated cone biopsied carcinoma in situ of the cervix or basal cell or squamous cell skin cancer
• No ongoing or active infection
• No diabetes mellitus (with evidence of severe peripheral vascular disease or ulcers)
• No psychiatric illness or social situation that would preclude study compliance
• No other uncontrolled illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 4 weeks since prior immunotherapy
• Concurrent epoetin alfa allowed

Chemotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
• No prior 17-N-allylamino-17-demethoxygeldanamycin (17-AAG)

Endocrine therapy

• More than 4 weeks since prior endocrine therapy
• Concurrent luteinizing hormone-releasing hormone analogues for androgen-insensitive prostate cancer and rising prostate-specific antigen allowed

Radiotherapy

• More than 4 weeks since prior radiotherapy (except for palliative treatment)
• No prior irradiation field that potentially included the heart (e.g., mantle)

Surgery

• Not specified

Other

• Recovered from all prior therapy
• Concurrent bisphosphonates allowed
• At least 5 half-lives since prior and no concurrent medication that prolong QTc
• No other concurrent anticancer or investigational agents
• No concurrent grapefruit juice