Geldanamycin Analogue in Treating Patients With Advanced Cancer

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: This phase I trial is studying the side effects and best dose of a geldanamycin analogue in treating patients with advanced cancer.

OBJECTIVES:

* Determine the maximum tolerated dose for a geldanamycin analogue, 17-allylamino-17-demethoxygeldanamycin (AAG), in patients with advanced malignancies.
* Determine the toxic effects and dose-limiting toxicity of AAG in this patient population.
* Determine the safe dose of AAG for a Phase II study.
* Measure the pharmacokinetic and pharmacodynamic profiles of AAG in these patients.
* Assess time to tumor progression and any antitumor activity in patients treated with AAG.

OUTLINE: This is a dose-escalation study.

Patients receive a geldanamycin analogue, 17-allylamino-17-demethoxygeldanamycin (AAG), IV over 15-30 minutes every week. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of AAG until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.

Patients are followed at 4 weeks.

PROJECTED ACCRUAL: Approximately 20-40 patients will be accrued for this study.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Histologically or cytologically proven malignancies refractory to conventional treatment or for which no standard therapy exists
* Primary brain tumor or brain metastases allowed if stable symptoms within 2 weeks prior to study and able to give informed consent

PATIENT CHARACTERISTICS:

Age:

* 18 to 75

Performance status:

* WHO 0-2

Life expectancy:

* At least 3 months

Hematopoietic:

* WBC at least 3,500/mm\^3
* Platelet count at least 100,000/mm\^3
* Hemoglobin at least 10.0 g/dL
* Absolute neutrophil count at least 1,500/mm\^3

Hepatic:

* Bilirubin less than 1.0 mg/dL
* AST and ALT no greater than 2.5 times upper limit of normal if due to liver metastases
* No chronic liver disease

Renal:

* Creatinine less than 1.47 mg/dL OR
* Creatinine clearance greater than 60 mL/min

Cardiovascular:

* No myocardial infarction within the past 6 months
* No angina requiring treatment within the past 6 months
* No uncompensated coronary artery disease by electrocardiogram or physical examination
* No prior transient ischemic attacks, stroke, or peripheral vascular disease
* LVEF at least 45%

Other:

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 4 weeks after study
* No allergy to egg products
* No nonmalignant systemic disease that would increase risk
* No active uncontrolled infection
* No diabetes mellitus with evidence of severe peripheral vascular disease or diabetic ulcers

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* At least 4 weeks since prior immunotherapy and recovered

Chemotherapy:

* At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin) and recovered
* No other concurrent chemotherapy

Endocrine therapy:

* At least 4 weeks since other prior endocrine therapy and recovered
* Concurrent corticosteroids for symptom control allowed if no change in dose requirement within 2 weeks prior to study

Radiotherapy:

* At least 4 weeks since prior radiotherapy (except for palliative reasons) and recovered
* Concurrent radiotherapy allowed for control of bone pain or as indicated

Surgery:

* Not specified

Other:

* No other concurrent investigational treatment
* No concurrent treatment with drugs interfering with hepatic CYP3A4 metabolism (e.g., grapefruit juice or warfarin)