Clinical Trial: Study of (1) Everolimus, (2) Estrogen Deprivation Therapy (EDT) With Leuprolide + Letrozole and (3) Everolimus + EDT in Patients With Unresectable Fibrolamellar Hepatocellular Carcinoma (FLL-HCC)

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Randomized Three Arm Phase II Study of (1) Everolimus, (2) Estrogen Deprivation Therapy (EDT) With Leuprolide + Letrozole and (3) Everolimus + EDT in Patients With Unresectable

Brief Summary: There is no effective standard treatment for fibrolamellar liver cancer that cannot be removed by surgery. The investigators want to find out what effects, good and/or bad, 3 drugs called letrozole, leuprolide and everolimus will have on cancer. All of these drugs are FDA approved for the treatment of different cancers. Letrozole and leuprolide stop the body from producing estrogen, a normal hormone produced by the body. Too much estrogen may help fibrolamellar liver cancer grow. Everolimus is a drug that may block other chemicals in the body that can help cancer grow. The combination of letrozole and leuprolide plus everolimus may work well together.

Detailed Summary:
Sponsor: Memorial Sloan Kettering Cancer Center

Current Primary Outcome: efficacy endpoints for Part 1 of the study is progression-free survival at 6 months (PFS6) [ Time Frame: 6 months ]

for Part 1 of the study is progression-free survival at 6 months (PFS6). A progression event refers to the first evidence of radiographic disease progression, clinical progression as determined by study investigators, or death. Imaging performed in 6 months will be used to determine PFS6.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • median PFS [ Time Frame: 2 years ]
    Kaplan-Meier PFS will be measured from the date that study therapy is initiated until the date of first evidence of radiographic disease progression, global clinical deterioration as determined by study investigators, or death.
  • median overall survival (OS) [ Time Frame: 2 years ]
    Kaplan-Meier OS will be measured from the date that study therapy was commenced until the date of death.
  • response rate [ Time Frame: 2 years ]
    Objective responses will be reported using RECIST guidelines (version 1.1). Objective response will be estimated using binomial proportions and exact 95% CIs will be provided.
  • to evaluate toxicity in patients [ Time Frame: 2 years ]
    Adverse events/toxicity will be monitored and recorded using the CTCAE version 4.0 and summarized descriptively.
  • correlative serum [ Time Frame: 2 years ]
    Baseline serum measurements will be correlated with PFS6 (binary endpoint) using Fisher's exact test for categorical serum measurements and using Wilcoxon rank sum test for continuous measurements. For each time point at which serum measurements are collected, changes in the different binary serum markers from baseline will be correlated with PFS6 using conditional logistic regression to account for the paired nature of the data while Wilcoxon signed-rank test will be used for continuous measurements.
  • tissue biomarker studies [ Time Frame: 2 years ]
    Associations between baseline tissue biomarkers and PFS6 will be assessed using Fisher's exact test for categorical biomarkers, trend tests for ordinal biomarkers and Wilcoxon rank-sum test for continuous biomarkers. For patients undergoing surgery, changes in tissue biomarkers from baseline to surgery will be summarized descriptively in an exploratory fashion.
  • to evaluate safety in patients [ Time Frame: 2 years ]
    Adverse events/toxicity will be monitored and recorded using the CTCAE version 4.0 and summarized descriptively.


Original Secondary Outcome: Same as current

Information By: Memorial Sloan Kettering Cancer Center

Dates:
Date Received: July 12, 2012
Date Started: July 2012
Date Completion: July 2017
Last Updated: August 15, 2016
Last Verified: August 2016