OBJECTIVES:

• Determine the maximum tolerated dose of geldanamycin analogue (AAG) in patients with advanced solid tumors.
• Determine the toxic effects of this drug in this patient population.
• Determine the biochemical and molecular effects of this drug in normal and accessible tumor tissue in these patients.
• Determine the pharmacokinetics of this drug in these patients.
• Assess any antitumor activity of this drug in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive geldanamycin analogue (AAG) IV over 1-6 hours once daily on days 1, 4, 15, and 18. Courses repeat every 4 weeks 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 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional 10 patients are treated at the MTD.

Patients are followed every 6 weeks.

PROJECTED ACCRUAL: A total of 45 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed advanced solid tumor for which no curative therapy exists

  • Non-Hodgkin's lymphoma allowed
• No leukemia
• No active CNS involvement with tumor

PATIENT CHARACTERISTICS:

Age:

• 19 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 3 months

Hematopoietic:

• Absolute neutrophil count at least 2,000/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin ≤ upper limit of normal (ULN)
• AST no greater than 2 times ULN (no greater than 98 U/L)

Renal:

• Creatinine ≤ ULN OR
• Creatinine clearance at least 60 mL/min

Cardiovascular

• None of the following significant cardiac diseases:

  • New York Heart Association class III or IV heart failure
  • History of myocardial infarction within the past year
  • Uncontrolled dysrhythmias
  • Poorly controlled angina
• No serious ventricular arrhythmia (i.e., ventricular tachycardia (VT) or ventricular fibrillation (VF) ≥ 3 beats in a row)
• QTc interval ≤ 450 msec for men or ≤ 470 msec for women
• LVEF ≥ 40% by MUGA

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No other serious medical condition that would preclude study participation
• No serious hypersensitivity to egg products

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No concurrent anticancer immunotherapy

Chemotherapy:

• At least 4 weeks since prior chemotherapy and recovered
• No other concurrent anticancer chemotherapy (e.g., cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP] or mechlorethamine, vincristine, procarbazine, and prednisone [MOPP])

Endocrine therapy:

• No concurrent anticancer hormonal therapy

• No concurrent anticancer glucocorticoids

  • Concurrent glucocorticoids as antiemetics for nonmalignant disease allowed

Radiotherapy:

• At least 4 weeks since prior radiotherapy and recovered
• No concurrent radiotherapy

Surgery:

• No concurrent major surgery

Other:

• No concurrent drugs that interfere with hepatic CYP3A4 metabolism (e.g., grapefruit juice, ketoconazole, fluconazole, itraconazole, cyclosporine, erythromycin, clarithromycin, cimetidine, terfenadine, astemizole, indinavir, or nelfinavir mesylate)
• No concurrent medications that cause QTc prolongation