RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase I trial to study the effectiveness of suberoylanilide hydroxamic acid in treating patients who have advanced primary or metastatic solid tumors that have not responded to previous therapy.

Condition	Treatment or Intervention	Phase
Leukemia Lymphoma Prostate Cancer Multiple Myeloma Eye Cancer	Procedure: chemotherapy  Drug: suberoylanilide hydroxamic acid	Phase I

Further Study Details: 

OBJECTIVES: I. Determine the maximum tolerated dose of suberoylanilide hydroxamic acid (SAHA) in patients with advanced malignancies. II. Assess the pharmacokinetic profile of SAHA in these patients. III. Assess the biologic effects of SAHA on normal tissues and on tumor cells in these patients.

PROTOCOL OUTLINE: This is a dose-escalation study. Patients receive suberoylanilide hydroxamic acid (SAHA) IV over 2 hours for 3 consecutive days. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. Accelerated Phase: One patient per dose level receives escalating doses of SAHA until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which a patient experiences grade 2 or greater toxicity (other than hemoglobin anemia) with the first course, or when 2 different patients experience a grade 2 toxicity (other than hemoglobin anemia) during any course of treatment. Standard Phase: Cohorts of 3-6 patients receive escalating doses of SAHA until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: Approximately 45 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed advanced primary or metastatic malignancy refractory to standard therapy or for which no curative therapy exists
• No progressive metastatic disease requiring palliative therapy within 4 weeks of study
• Progressive disease; Increase in preexisting lesions on imaging or physical examination Patients with sole progression criterion of increased biochemical marker (e.g., carcinoembryonic antigen or CA 15-3) or increased symptoms not eligible
• Prostate cancer must be either progressive metastatic disease on imaging studies or have rising PSA values; Minimum of 3 rising PSA values obtained at least 1 week apart, or 2 rising PSA values more than 1 month apart, with at least a 25% overall increase; Serum testosterone less than 50 ng/mL; Must maintain castrate status
• No active CNS or epidural tumor

--Prior/Concurrent Therapy--

• Biologic therapy: Recovered from prior biologic therapy
• Chemotherapy: At least 4 weeks since prior chemotherapy and recovered
• Endocrine therapy: Recovered from prior endocrine therapy; No concurrent ketoconazole in patients with prostate cancer
• Radiotherapy: At least 4 weeks since prior radiotherapy and recovered; No concurrent radiotherapy to target lesions
• Surgery: Not specified
• Other: At least 4 weeks since other prior investigational anticancer drugs and recovered

--Patient Characteristics--

• Age: 18 and over
• Performance status: Karnofsky 70-100%
• Life expectancy: Not specified
• Hematopoietic: WBC at least 3,500/mm3; Platelet count at least 100,000/mm3
• Hepatic: Bilirubin no greater than 1.0 mg/dL; AST no greater than 37 U/L; PTT no greater than 14 seconds
• Renal: Creatinine no greater than 2.0 mg/dL
• Cardiovascular: No significant cardiac disease (i.e., New York Heart Association class III or IV)
• Pulmonary: No severe debilitating pulmonary disease
• Other: No infection requiring IV antibiotic treatment; No other severe medical problems that would preclude study; Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception

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

Study chairs or principal investigators

William K. Kelly,  Study Chair,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000067789; MSKCC-99059; NCI-H00-0051
Record last reviewed:  December 2003
Last Updated:  October 13, 2004
Record first received:  May 2, 2000
ClinicalTrials.gov Identifier:  NCT00005634
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08