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