MS-275 in Treating Patients With Advanced Solid Tumors or Lymphoma
RATIONALE: MS-275 may stop the growth of cancer cells by blocking the enzymes necessary for their growth.
PURPOSE: This phase I trial is studying the side effects and best dose of MS-275 in treating patients with advanced solid tumors or lymphoma.
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of an Oral Histone Deacetylase Inhibitor, MS-275, in Refractory Solid Tumors and Lymphomas|
- Dose-limiting toxicities and maximum tolerated dose [ Designated as safety issue: Yes ]
- Pharmacology and pharmacokinetics [ Designated as safety issue: No ]
- Acetylation of histones in peripheral blood [ Designated as safety issue: No ]
- Tumor response by CT scan every 12 weeks [ Designated as safety issue: No ]
|Study Start Date:||March 2001|
|Study Completion Date:||October 2008|
|Primary Completion Date:||April 2008 (Final data collection date for primary outcome measure)|
- 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.
|United States, Maryland|
|National Naval Medical Center|
|Bethesda, Maryland, United States, 20889-5000|
|NCI - Center for Cancer Research|
|Bethesda, Maryland, United States, 20892|
|Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support|
|Bethesda, Maryland, United States, 20892-1182|
|Principal Investigator:||Shivaani Kummar, MD||NCI - Medical Oncology Branch|