Clinical Trial: MS-275 and Isotretinoin in Treating Patients With Metastatic or Advanced Solid Tumors or Lymphomas
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: A Phase I Study of an Oral Histone Deacetylase Inhibitor, MS-275 (NSC 706995, IND 61,198), in Combination With 13-Cis-Retinoic Acid in Metastatic Progressive Cancer.
Brief Summary: Phase I trial to study the effectiveness of combining MS-275 with isotretinoin in treating patients who have metastatic or advanced solid tumors or lymphomas. MS-275 may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Isotretinoin may help cancer cells develop into normal cells. MS-275 may increase the effectiveness of isotretinoin by making cancer cells more sensitive to the drug. MS-275 and isotretinoin may also stop the growth of solid tumors or lymphomas by stopping blood flow to the cancer. Combining MS-275 with isotretinoin may kill more cancer cells
Detailed Summary:
PRIMARY OBJECTIVES:
I. Determine the dose-limiting toxicity and maximum tolerated dose of MS-275 when administered with isotretinoin in patients with metastatic, progressive, refractory, or unresectable solid tumors or lymphomas.
SECONDARY OBJECTIVES:
I. Determine, preliminarily, tumor response in patients treated with this regimen.
II. Determine the pharmacokinetic profile of this regimen in these patients.
OUTLINE: This is an open-label, dose-escalation study of MS-275.
Patients receive oral MS-275 once on days 1, 8, and 15 and oral isotretinoin twice daily on days 1-21. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Cohorts of 3-6 patients receive escalating doses of MS-275 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 dose-limiting toxicity. Up to 12 patients are treated at the MTD.
Patients are followed monthly.
Sponsor: National Cancer Institute (NCI)
Current Primary Outcome:
- Dose limiting toxicities defined as an adverse event which is likely related to the study medication [ Time Frame: 28 days ]Graded using the CTCAE version 3.0.
- Maximum tolerated dose of entinostat and isotretinoin in combination [ Time Frame: 28 days ]
Original Primary Outcome:
Current Secondary Outcome:
- Pharmacokinetics [ Time Frame: Up to day 21 of course 2 ]
- Adverse events defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment [ Time Frame: Up to 30 days after completion of study treatment ]Graded using the CTCAE version 3.0. Summarized by dose level.
Original Secondary Outcome:
Information By: National Cancer Institute (NCI)
Dates:
Date Received: December 8, 2004
Date Started: October 2004
Date Completion:
Last Updated: January 23, 2013
Last Verified: January 2013