Clinical Trial: MK2206 in Treating Younger Patients With Recurrent or Refractory Solid Tumors or Leukemia

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase I Study of MK-2206, an AKT Inhibitor, in Pediatric Patients With Recurrent or Refractory Solid Tumors or Leukemia

Brief Summary: This phase I trial is studying the side effects, best way to give, and best dose of Akt inhibitor MK2206 (MK2206) in treating patients with recurrent or refractory solid tumors or leukemia. MK2206 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Detailed Summary:

PRIMARY OBJECTIVES:

l. To estimate the maximum-tolerated dose (MTD) and/or recommended phase 2 dose of MK-2206 (Akt inhibitor MK2206) administered orally every other day (schedule 1) or once weekly (schedule 2) to children with refractory or recurrent solid malignancies, including central nervous system (CNS) tumors or lymphomas.

II. To define and describe the toxicities of MK-2206 in children with refractory solid malignancies administered on this schedule.

III. To assess the tolerability of MK-2206 at the solid tumor MTD in patients with recurrent or refractory leukemia.

IV. To characterize the pharmacokinetics of MK-2206 in children with recurrent or refractory cancer. (exploratory)

SECONDARY OBJECTIVES:

I. To preliminarily define the antitumor activity of MK-2206 within the confines of a phase 1 study.(exploratory) II. To evaluate biological activity of MK-2206 by measuring phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling in tumor and peripheral blood mononuclear cells and measure the expression of biomarkers related to AKT activation phenotypes. (exploratory)

OUTLINE: This is a dose-escalation study (part A) followed by treatment at the maximum-tolerated dose (part B).

Patients receive Akt inhibitor MK2206 orally (PO) every other day (schedule 1) OR once weekly (schedule 2) on days 1-28. Treatment repeats every 28 days for up 12 courses (1 year) in the absence of disease progression or unacceptable toxicity.

After com
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: MTD and/or recommended phase 2 dose of Akt inhibitor MK2206 determined according to incidence of dose-limiting toxicities (DLTs) graded using CTCAE v4.0 (Part A) [ Time Frame: 28 days ]

The MTD will be the maximum dose at which fewer than one-third of patients experience DLT during course 1 of therapy.


Original Primary Outcome:

  • Maximum-tolerated dose (MTD) and/or recommended phase 2 dose of Akt inhibitor MK2206
  • Toxicities of this treatment in children with refractory solid malignancies administered on this schedule
  • Tolerability of this treatment at the solid tumor MTD in patients with recurrent or refractory leukemia


Current Secondary Outcome:

  • Pharmacokinetic (PK) parameters of Akt inhibitor MK-2206 [ Time Frame: Baseline, 0.5, 1.5, 3, 6-8, 24, 48 hours day 1 course 1; pre-dose and 6-8 hours post-dose (optional) day 15 (Schedule 1); baseline, 0.5, 1.5, 3, 6-8, 24, 48 hours day 1 course 1; pre-dose days 8 and 15; 6-8 hours post-dose day 15 (optional) (Schedule 2) ]
    Summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).
  • Antitumor activity assessed by Response Evaluation Criteria for Solid Tumors (RECIST) 1.1 [ Time Frame: Up to 30 days ]
  • Levels of activation of downstream signaling molecules [ Time Frame: Up to day 15 of course 1 ]
    Summarized using descriptive statistics at each timepoint. The Wilcoxon signed-rank test or Friedman's test may be used as a preliminary test of change in activity over two or more timepoints.
  • Mutations or amplification of upstream signaling molecules [ Time Frame: Baseline ]
    Summarized using descriptive statistics at each timepoint. The Wilcoxon signed-rank test or Friedman's test may be used as a preliminary test of change in activity over two or more timepoints.


Original Secondary Outcome:

Information By: National Cancer Institute (NCI)

Dates:
Date Received: October 29, 2010
Date Started: January 2011
Date Completion:
Last Updated: April 28, 2014
Last Verified: April 2013