Clinical Trial: Entinostat and Sorafenib Tosylate in Treating Patients With Advanced or Metastatic Solid Tumors or Refractory or Relapsed Acute Myeloid Leukemia

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Phase I Study of Sorafenib in Combination With the Histone Deacetylase Inhibitor, Entinostat in Patients With Advanced Cancers

Brief Summary: This phase I trial is studying the side effects and the best dose of entinostat when given together with sorafenib tosylate in treating patients with advanced or metastatic solid tumors or refractory or relapsed acute myeloid leukemia. Entinostat and sorafenib tosylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine the maximum-tolerated dose of entinostat in combination with sorafenib tosylate in patients with advanced, inoperable, or metastatic solid tumors.

II. To determine the safety and tolerability of this regimen in these patients.

SECONDARY OBJECTIVES:

I. To determine the pharmacokinetic profile of this regimen in patients with refractory/relapsed acute myeloid leukemia (AML).

II. To assess the preliminary anti-tumor activity of this regimen in patients with advanced, inoperable, or metastatic solid tumors or refractory/relapsed AML.

III. To evaluate histone deacetylase (HDAC) inhibition of histone acetylation in leukemia blast cells.

TERTIARY OBJECTIVES (EXPLORATORY):

I. To evaluate the expression of downstream markers of drug activity such as p38, MCL-1, FLT-3, and VEGFR-2 in leukemia blast cells.

II. To evaluate SNDX-induced expression of p21^WAF1/CIP1 in leukemia blast cells.

OUTLINE: This is a multicenter, dose-escalation study of entinostat.

Patients receive oral entinostat once daily on days 1 and 15 and oral sorafenib tosylate twice daily on days 1-28 (days 15-28 only of course 1). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients in the expansion cohort undergo blood, bone marrow aspiration, or biopsy for pharmacokinetic studies and biomarke
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • Maximum-tolerated dose as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: 28 days ]
  • Safety as assessed by the NCI CTCAE version 4.0 [ Time Frame: Up to 30 days ]


Original Primary Outcome:

  • Maximum-tolerated dose
  • Safety and tolerability


Current Secondary Outcome:

  • Pharmacokinetic profile of sorafenib tosylate [ Time Frame: At baseline, and at days 15, 16, and 28 of course 1, and day 1 of course 2 ]
  • Pharmacokinetic profile of entinostat [ Time Frame: At baseline and at days 1, 8, 15, 16, and 22 ]
  • Objective response rate (ORR) based on the best overall response recorded for each patients or according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [ Time Frame: Up to 30 days ]
    For ORR the 95% confidence interval will be estimated. The 95% confidence interval for percent of patients in each RECIST response category (i.e., CR, PR, SD, and PD) and disease control rate will also be estimated.


Original Secondary Outcome:

  • Pharmacokinetic profile
  • Objective response


Information By: National Cancer Institute (NCI)

Dates:
Date Received: July 8, 2010
Date Started: June 2010
Date Completion:
Last Updated: September 18, 2013
Last Verified: September 2013