Clinical Trials Directory

Trials / Completed

CompletedNCT01935973

Trametinib With or Without GSK2141795 in Treating Patients With Recurrent or Persistent Endometrial Cancer

A Randomized Phase I Study With a Safety Lead-In to Assess the Antitumor Efficacy of the MEK Inhibitor Trametinib Alone or in Combination With GSK2141795, an AKT Inhibitor, in Patients With Recurrent or Persistent Endometrial Cancer NCT #01935973

Status
Completed
Phase
Phase 1
Study type
Interventional
Enrollment
26 (actual)
Sponsor
National Cancer Institute (NCI) · NIH
Sex
Female
Age
18 Years
Healthy volunteers
Not accepted

Summary

This randomized phase I trial studies how well trametinib with or without GSK 2141795 (protein kinase B \[Akt\] inhibitor GSK2141795) works in treating patients with endometrial cancer that has come back (recurrent) or does not go to remission despite treatment (persistent). Trametinib and Akt inhibitor GSK2141795 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether trametinib is a more effective treatment for endometrial cancer when given with or without ATK inhibitor GSK2141795.

Detailed description

PRIMARY OBJECTIVES: I. To assess the relative activity of trametinib (mitogen-activated protein kinase \[MEK\] inhibitor) alone or in combination with GSK2141795 (AKT inhibitor) for patients with recurrent or persistent endometrial cancer by progression-free survival. (Phase II) II. To determine the frequency and severity of adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE). (Phase II) III. To determine the tolerability of the combination regimen of trametinib and GSK2141795 through determination of dose-limiting toxicity in a two-stage safety lead in study. (Safety assessment lead-in) SECONDARY OBJECTIVES: I. To estimate the association between baseline Kirsten rat sarcoma viral oncogene homolog (KRAS) status and clinical activity (e.g. response and progression-free survival \[PFS\]) for patients with recurrent or persistent endometrial cancer who are treated with trametinib alone or in combination with GSK2141795. II. To estimate overall survival (OS) of patients with recurrent or persistent endometrial cancer treated with trametinib therapy alone (excluding patients who cross-over) and trametinib/GSK2141795 combination therapy in the two subgroups of patients defined above. III. Prognostic factors will be examined for associations with patients who do not crossover. IV. To estimate objective response and response duration associated with trametinib therapy and trametinib/GSK2141795 combination therapy in the two subgroups of patients defined above. V. To estimate the relative proportion of patients responding or have 6-month PFS on the therapies administered on this study with those studies that may serve as a historical control. TERTIARY OBJECTIVES: I. To estimate the association between baseline genomic biomarkers in the phosphatidylinositol 3 kinase (PI3K)/AKT pathway and clinical activity (e.g. response and PFS) in two subgroups of patients defined above with recurrent or persistent endometrial cancer who are treated with trametinib alone or in combination with GSK2141795. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive trametinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving disease progression may cross over to Arm II. ARM II: Patients receive trametinib PO QD and Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Conditions

Interventions

TypeNameDescription
OTHERLaboratory Biomarker AnalysisCorrelative studies
DRUGTrametinibGiven PO
DRUGUprosertibGiven PO

Timeline

Start date
2013-09-30
Primary completion
2015-09-08
Completion
2015-09-08
First posted
2013-09-05
Last updated
2020-10-14

Locations

22 sites across 1 country: United States

Source: ClinicalTrials.gov record NCT01935973. Inclusion in this directory is not an endorsement.