Phase I Clinical and Pharmacological Study of Suberoylanilide Hydroxamic Acid- SAHA (MSK390) in Patients With Advanced Solid Tumors
18 Years
N/A
Both
Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Prostate Cancer, Small Intestine Cancer, Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
Phase I Clinical and Pharmacological Study of Suberoylanilide Hydroxamic Acid- SAHA (MSK390) in Patients With Advanced Solid Tumors
OBJECTIVES: I. Determine the maximum tolerated dose of suberoylanilide hydroxamic acid
(SAHA) in patients with refractory 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.
OUTLINE: This is a dose-escalation study. Patients receive suberoylanilide hydroxamic acid
(SAHA) IV over 2 hours on days 1-3. 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.
Inclusion Criteria
DISEASE CHARACTERISTICS: Histologically confirmed 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
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 PT no
greater than 14 seconds Renal: Creatinine no greater than 2.0 mg/dL Cardiovascular: No
significant cardiac disease No New York Heart Association class III or IV heart disease
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
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 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 No concurrent ketoconazole in patients with prostate cancer
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
William K. Kelly, DO
Investigator Role:
Study Chair
Investigator Affiliation:
Memorial Sloan-Kettering Cancer Center
Authority:
United States: Federal Government
Study ID:
99-059
NCT ID:
NCT00005634
Start Date:
January 2000
Completion Date:
October 2002
Related Keywords:
- Leukemia
- Lymphoma
- Multiple Myeloma and Plasma Cell Neoplasm
- Prostate Cancer
- Small Intestine Cancer
- Unspecified Adult Solid Tumor, Protocol Specific
- recurrent adult Hodgkin lymphoma
- recurrent cutaneous T-cell non-Hodgkin lymphoma
- isolated plasmacytoma of bone
- extramedullary plasmacytoma
- refractory multiple myeloma
- recurrent adult acute myeloid leukemia
- recurrent adult acute lymphoblastic leukemia
- relapsing chronic myelogenous leukemia
- refractory chronic lymphocytic leukemia
- small intestine lymphoma
- recurrent prostate cancer
- unspecified adult solid tumor, protocol specific
- chronic phase chronic myelogenous leukemia
- refractory hairy cell leukemia
- chronic myelomonocytic leukemia
- recurrent grade 1 follicular lymphoma
- recurrent grade 2 follicular lymphoma
- recurrent grade 3 follicular lymphoma
- recurrent adult diffuse small cleaved cell lymphoma
- recurrent adult diffuse mixed cell lymphoma
- recurrent adult diffuse large cell lymphoma
- recurrent adult immunoblastic large cell lymphoma
- recurrent adult lymphoblastic lymphoma
- recurrent adult Burkitt lymphoma
- recurrent adult T-cell leukemia/lymphoma
- secondary acute myeloid leukemia
- recurrent mantle cell lymphoma
- recurrent mycosis fungoides/Sezary syndrome
- recurrent marginal zone lymphoma
- recurrent small lymphocytic lymphoma
- extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
- nodal marginal zone B-cell lymphoma
- splenic marginal zone lymphoma
- Neoplasms
- Leukemia
- Lymphoma
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Plasmacytoma
- Prostatic Neoplasms
- Duodenal Neoplasms
- Ileal Neoplasms
- Jejunal Neoplasms
- Intestinal Neoplasms
Name | Location |
|---|---|
| Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
