Biospecimen Collection in Assessing the Effect of Trametinib With or Without Uprosertib on Biomarkers in Patients With Persistent or Recurrent Endometrial Cancer Enrolled on Trial GOG02290

A Translational Companion Protocol to GOG229O: A Randomized Phase II 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

This trial assesses blood and tumor samples for the effect of trametinib with or without uprosertib on biomarkers in patients enrolled on trial GOG02290 with endometrial cancer that is persistent or has come back. Biomarkers found in the blood and tissue may be related to the reaction or response to the study drugs.

Study Overview

• Status: Completed
• Conditions: Recurrent Endometrial Carcinoma
• Intervention / Treatment: Procedure: Biospecimen Collection

Detailed Description

PRIMARY OBJECTIVES:

I. To explore the impact of trametinib alone or in combination with uprosertib (GSK2141795) on RAF-MEK-ERK and PI3K pathway signaling.

SECONDARY OBJECTIVES:

I. To examine associations with early changes in functional proteomic biomarkers in tumor biopsies before and after treatment and tumor response in two subgroups of patients with recurrent or persistent endometrial cancer who are treated with trametinib alone or in combination with GSK2141795.

II. To examine levels of circulating tumor cells in blood samples before and after treatment and correlate with tumor response in two subgroups of patients with recurrent or persistent endometrial cancer who are treated with trametinib alone or in combination with GSK2141795.

III. To examine the bRaf/cRaf dimer or Raf/KSR/Mek1 dimers in paraffin sections from these patients before treatment by proximity ligation assay (PLA) assays.

IV. To quantify exosomes from these patients before and after treatment by enzyme-linked immunosorbent assay (ELISA) assay with CD63 antibody and explore bRaf/cRaf dimer or Raf/KSR/Mek1 dimers in exosomes from these patients before and after treatment by PLA assays.

OUTLINE:

Patients undergo collection of blood at screening, between days 3 and 5, 28, and 56. Patients also undergo collection of tumor biopsy at screening and day 28.

• Study Type: Observational
• Enrollment (Anticipated): 40

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

MDACC Participants

Description

Inclusion Criteria:

• Patients must be enrolled on GOG0229O
• Patients must have tissue available for molecular analysis. This can be tissue obtained at time of current recurrence or archival tissue from primary diagnosis or recurrence
• Patients must have disease lesions that are amenable to pre- and post- treatment biopsy
• Patients must have signed an approved informed consent and authorization permitting release of personal health information

Exclusion Criteria:

• Patients unwilling to undergo a biopsy

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Ancillary-correlative (Biospecimen collection); Patients undergo collection of blood at screening, between days 3 and 5, 28, and 56. Patients also undergo collection of tumor biopsy at screening and day 28.	Procedure: Biospecimen Collection; Undergo collection of blood and tumor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in biomarker expression	Will use descriptive statistics and graphical methods to compare pre-treatment to post-treatment changes in biomarker expression between patients with and without each type of response for each treatment arm and subgroup. Will estimate mean changes from pre-treatment to each post-treatment assessment with 95% confidence intervals. will use a 2-sample t-test to compare treatment arms with respect to the mean change in biomarker expression. Will use a 2-sample Wilcoxon rank sum test to compare treatment arms with respect to the median change in biomarker expression. This testing may also be restricted to specific subgroups (e.g., patients with complete response), depending on the characteristics of patients accrued. Will also use regression methods to model the change in biomarker expression with time and type of response.	Pre-treatment to post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Circulating tumor cells (CTCs) levels	Will use descriptive statistics and graphical methods to compare the numbers of circulating tumor cells (CTCs) over time for patients with and without each type of response for each treatment arm and subgroup. Will estimate with 95% confidence intervals the mean number of CTCs at each assessment time for patients with and without each type of response for each treatment arm and subgroup.	Up to 15 years

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Shannon Westin, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• MD Anderson Cancer Center Website

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2004
• Primary Completion (Actual): January 15, 2020
• Study Completion (Actual): January 15, 2020

Study Registration Dates

• First Submitted: March 17, 2014
• First Submitted That Met QC Criteria: March 19, 2014
• First Posted (Estimate): March 21, 2014

Study Record Updates

• Last Update Posted (Actual): January 28, 2020
• Last Update Submitted That Met QC Criteria: January 24, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Disease Attributes; Recurrence; Endometrial Neoplasms
• Other Study ID Numbers: 2013-1029 (Other Identifier: M D Anderson Cancer Center); P30CA016672 (U.S. NIH Grant/Contract); NCI-2018-02663 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No