OBJECTIVES: I. Determine the maximum tolerated dose and recommended phase II dose of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) when administered with paclitaxel in patients with metastatic or unresectable solid malignancy. II. Determine the dose-limiting and non-dose-limiting toxic effects of this regimen in these patients. III. Determine the pharmacokinetics of this regimen in these patients. IV. Determine tumor response in patients treated with this regimen. OUTLINE: This is a multicenter, dose-escalation study of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG). Patients receive 17-AAG IV over 1 hour on days 1\*, 4, 8, 11, 15 and 18 and paclitaxel IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. NOTE: \*17-AAG is not administered on day 1 of course 1. Cohorts of 3-6 patients receive escalating doses of 17-AAG 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. Once the MTD is determined, 6-12 patients are treated at the recommended phase II dose.
Inclusion Criteria: * Histologically confirmed solid malignancy * Metastatic or unresectable disease * Not amenable to standard curative or palliative therapy * No known brain metastases * Performance status - ECOG 0-2 * More than 12 weeks * 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 * Bilirubin normal * Creatinine normal * Creatinine clearance ≥ 60 mL/min * QTc \< 450 msec for male patients (470 msec for female patients) * LVEF \> 40% by MUGA * No history of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row) * No myocardial infarction within the past year * No New York Heart Association class III or IV congestive heart failure * No poorly controlled angina * No history of uncontrolled dysrhythmia or requirement for antiarrhythmic drugs * No history of congenital long QT syndrome * No active ischemic heart disease within the past year * No left bundle branch block * No other significant cardiac disease * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective double barrier contraception for at least 1 week before, during, and for at least 2 weeks after study participation * No prior allergy to eggs * No prior allergic reaction to compounds of similar chemical or biologic composition to 17-AAG or paclitaxel * No peripheral neuropathy \> grade 1 * No concurrent uncontrolled illness * No active or ongoing infection * No psychiatric illness or social situation that would preclude study compliance * No concurrent granulocyte colony-stimulating factors * Prior paclitaxel allowed * More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered * No prior 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) * More than 4 weeks since prior radiotherapy * No prior radiotherapy that included the heart in the field (e.g., mantle radiotherapy) * No concurrent combination antiretroviral therapy for HIV-positive patients * No concurrent therapeutic-dose warfarin for anticoagulation * No concurrent medications that may prolong QTc interval * No other concurrent investigational agents * No other concurrent anticancer agents or therapies
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