RATIONALE: Drugs used in chemotherapy, such as 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 metastatic or unresectable solid tumors.

Condition	Treatment or Intervention	Phase
Cancer	Drug: 17-dimethylaminoethylamino-17-demethoxygeldanamycin  Procedure: chemotherapy	Phase I

OBJECTIVES: Primary

• Determine the toxic effects and maximum tolerated dose of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) in patients with metastatic or unresectable solid tumors.

Secondary

• Determine the effects of this drug on the expression of Hsp90 client proteins in normal and tumor tissue samples from these patients.

OUTLINE: This is a dose-escalation study.

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

Cohorts of 1-2 patients receive accelerated escalating doses of 17-DMAG until at least 1 of 2 patients experience dose-limiting toxicity (DLT). Cohorts are then expanded to 3-6 patients who receive escalating doses (in a standard manner) 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 DLT. Once the MTD is determined, 10 additional patients are treated at that dose.

PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for this study.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed solid tumor, including, but not limited to, the following:
• Prostate
• Breast
• Ovary
• Colon
• Kidney
• Head and neck
• Stomach
• Melanoma
• Metastatic* or unresectable disease NOTE: *Metastatic disease, if present, should not be progressing so as to require palliative treatment within the next 4 weeks
• No standard curative or palliative therapy exists or is no longer effective
• Progressive disease as indicated by the following:
• Non-prostate cancer
• New lesions or increase in pre-existing lesions on bone scintigraphy, CT scan, MRI, or by physical examination
• No increase in biochemical markers (e.g., carcinoembryonic antigen or CA-15-3) or symptoms as sole evidence of disease progression
• Prostate cancer
• Must have castrate metastatic disease (i.e., disease progression after castration or treatment with a gonadotropin-releasing hormone [GnRH] analog)
• Patients who have not undergone surgical orchiectomy must continue with medical therapy (i.e., GnRH analogs) to maintain castrate levels of serum testosterone < 50 ng/dL
• Patients who received an antiandrogen as part of first-line hormonal therapy must show disease progression after discontinuing treatment
• Progressive metastatic disease on imaging studies (e.g., bone scan, CT scan, or MRI) OR metastatic disease and a rising prostate-specific antigen (PSA) allowed
• Biochemical progression is defined as a minimum of 3 rising PSA values from baseline obtained at least 1 week apart OR 2 rising PSA values obtained more than 1 month apart, with ≥ 25% increase in value
• No active brain metastases or epidural disease
• Hormone receptor status:
• Not specified

PATIENT CHARACTERISTICS: Age

• 18 and over

Sex

• Male or female

Menopausal status

• Not specified

Performance status

• Karnofsky 70-100% OR
• ECOG 0-1

Life expectancy

• More than 6 months

Hematopoietic

• WBC ≥ 3, 000/mm^3
• Absolute neutrophil count ≥ 1, 500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin normal
• AST and ALT ≤ 1.5 times upper limit of normal (ULN)
• PT normal

Renal

• Creatinine ≤ 1.4 mg/dL OR
• Creatinine clearance > 55 mL/min

Cardiovascular

• Ejection fraction ≥ 45% by radionuclide angiocardiography (RNCA) or echocardiography (ECHO)*
• No evidence of ventricular aneurysm by RNCA or ECHO*
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia NOTE: *Required for patients with a history or clinical findings requiring additional cardiac testing

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active or ongoing infection
• No symptomatic peripheral neuropathy ≥ grade 2
• No psychiatric illness or social situation that would preclude study compliance
• No other uncontrolled illness

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for mitomycin and nitrosoureas)

Endocrine therapy

• See Disease Characteristics
• At least 1 week since prior ketoconazole

Radiotherapy

• More than 4 weeks since prior radiotherapy

Surgery

• Not specified

Other

• Recovered from all prior therapy
• More than 4 weeks since prior investigational anticancer therapeutic drugs
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent administration of any of the following herbal remedies:
• Hydrastis canadensis (goldenseal)
• Hypericum perforatum (St. John's wort)
• Uncaria tomentosa (cat's claw)
• Echinacea angustifolia roots
• Trifolium pratense (wild cherry)
• Matricaria chamomila (chamomile)
• Glycyrrhiza glabra (licorice)
• Dillapiol
• Hypericin
• Naringenin
• No other concurrent investigational agents
• No other concurrent anticancer agents or therapies

New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting

Study chairs or principal investigators

David B. Solit, MD,  Study Chair,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000378288; MSKCC-04053; NCI-6542
Record last reviewed:  August 2004
Record first received:  August 4, 2004
ClinicalTrials.gov Identifier:  NCT00089362
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-10-29