A Phase I Study of an Oral Histone Deacetylase Inhibitor, MS-275, in Refractory Solid Tumors and Lymphomas
- Determine the dose-limiting toxicity and maximum tolerated dose of MS-275 in patients
with advanced solid tumors or lymphomas.
- Determine the profile of adverse events, including changes in laboratory parameters, in
patients treated with this drug.
- Assess the pharmacology and pharmacokinetics of this drug in these patients.
- Design MS-275 regimens with possibly more frequent dose administration based on the
pharmacology of MS-275 using the schedule in this study.
- Determine the antineoplastic activity of this drug in these patients.
OUTLINE: This is an open-label, dose-escalation study.
Patients receive oral MS-275 once on day 1. Courses repeat every 2 weeks (every 2-week
schedule). Alternatively, patients receive oral MS-275 once on days 1, 8, 15, and 22 (weekly
schedule). Courses repeat every 6 weeks. Treatment for both schedules continues in the
absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of MS-275 on the every 2-week schedule
until the maximum tolerated dose (MTD) is determined. Once the MTD for the every 2-week
schedule is determined, patients receive treatment on the weekly schedule as above. The MTD
is then determined for the weekly schedule. The MTD for both schedules is defined as the
dose preceding that at which at least 2 of up to 6 patients experience dose-limiting
toxicity. Once the MTD is determined for the weekly schedule, up to 3 additional patients
are accrued to receive MS-275 at the MTD of the weekly schedule.
Disease status is assessed every 3 months.
PROJECTED ACCRUAL: A total of 50-75 patients will be accrued for this study.
Masking: Open Label, Primary Purpose: Treatment
Dose-limiting toxicities and maximum tolerated dose
Shivaani Kummar, MD
NCI - Medical Oncology Branch
United States: Federal Government
|National Naval Medical Center||Bethesda, Maryland 20889|
|Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support||Bethesda, Maryland 20892-1182|
|NCI - Center for Cancer Research||Bethesda, Maryland 20892|