RATIONALE: Drugs used in chemotherapy, such as 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), work in different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of 17-DMAG in treating patients who have an advanced solid tumor or lymphoma.

Condition	Treatment or Intervention	Phase
adult solid tumor Leukemia Lymphoma small intestine cancer	Drug: 17-dimethylaminoethylamino-17-demethoxygeldanamycin  Procedure: chemotherapy	Phase I

OBJECTIVES: Primary

• Determine the maximum tolerated dose of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) in patients with an advanced malignant solid tumor or lymphoma.
• Determine the dose-limiting toxic effects and toxicity profile of this drug in these patients.

Secondary

• Compare the effects of this drug on heat shock protein 90 (Hsp90) client proteins when assayed in peripheral blood mononuclear cells (PBMC) vs tumor tissue from patients treated with this drug.
• Correlate disturbances in key signaling pathways with administration of this drug in these patients.
• Determine the dose that alters key proteins in the majority of patients treated with this drug.
• Correlate serum proteomic patterns with target interactions or DMAG clinical effects in patients treated with this drug.
• Determine the pharmacokinetics of this drug in these patients.

OUTLINE: This is a multicenter, dose-escalation study.

Patients receive 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) IV over 1 hour on days 2, 5, 9, 12, 16, 19, 23, and 26. Treatment repeats every 28 days for 8 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 1-6 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. Once the MTD is determined, 10 additional patients are treated at the MTD.

PROJECTED ACCRUAL: Approximately 40 patients will be accrued for this study within 2 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed malignant solid tumor OR lymphoma
• Metastatic or unresectable disease
• Standard curative or palliative measures are not available OR are associated with minimal survival benefit
• No known brain metastases
• Treated brain metastases allowed provided they have been stable ≥ 6 months without steroids or anti-seizure medications

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• More than 3 months

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• WBC ≥ 3,000/mm^3
• Hemoglobin > 8 g/dL

Hepatic

• AST and ALT ≤ upper limit of normal
• Bilirubin normal
• PT and PTT normal

Renal

• Creatinine normal OR
• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• No orthostatic hypotension > grade 2 (requiring more than brief fluid replacement or other therapy OR with physiological consequences)

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 2 months after study participation
• HIV negative
• No hyponatremia indicated by sodium < 130 mmol/L
• No known immunodeficiency syndromes
• No history of allergic reaction attributed to compounds of similar chemical or biological composition to 17-dimethylaminoethylamino-17-demethoxygeldanamycin (geldanamycin or 17-AAG)
• No concurrent uncontrolled illness
• No active or ongoing uncontrolled infection
• No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY: Biologic therapy

• More than 4 weeks since prior biologic therapy and recovered
• No concurrent prophylactic growth factors

Chemotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin, 8 weeks for UCN-01) and recovered

Endocrine therapy

• See Disease Characteristics
• Concurrent hormonal therapy for prostate cancer allowed provided patient has metastatic disease that has progressed despite prior hormonal therapy

Radiotherapy

• More than 4 weeks since prior radiotherapy and recovered

Surgery

• At least 4 weeks since prior major surgery

Other

• Concurrent bisphosphonates for any cancer allowed
• Concurrent preventative doses of aspirin or non-steroidal anti-inflammatory drugs allowed
• No concurrent full anticoagulation on a regular basis
• No concurrent prophylactic antiemetics
• No other concurrent investigational agents or therapies
• No other concurrent anticancer agents or therapies

Maryland
      Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support, Bethesda,  Maryland,  20892-1182,  United States; Recruiting

Study chairs or principal investigators

Barbara A. Conley, MD,  Study Chair,  National Cancer Institute (NCI)   
Patricia S. Steeg, PhD,  Principal Investigator,  National Cancer Institute (NCI)   

Study ID Numbers:  CDR0000377488; NCI-04-C-0218; NCI-6544
Record last reviewed:  August 2004
Record first received:  August 4, 2004
ClinicalTrials.gov Identifier:  NCT00088868
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-10-22