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)
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|ClinicalTrials.gov Identifier: NCT01642186|
Recruitment Status : Active, not recruiting
First Posted : July 17, 2012
Last Update Posted : August 18, 2017
|Condition or disease||Intervention/treatment||Phase|
|Fibrolamellar Carcinoma Fibrolamellar Liver Cancer||Drug: everolimus Drug: letrozole plus leuprolide Drug: combination of everolimus, letrozole and leuprolide||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||84 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||None (Open Label)|
|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 Fibrolamellar Hepatocellular Carcinoma (FLL-HCC)|
|Study Start Date :||July 2012|
|Estimated Primary Completion Date :||July 2018|
|Estimated Study Completion Date :||July 2018|
Experimental: Arm A everolimus
Everolimus will be administered at the following doses:
Experimental: Arm B letrozole plus leuprolide
Day 1 of Cycle 1: Leuprolide 7.5 mg IM will be administered by a nurse in clinic.
Letrozole will be dispensed and will be taken at home. Patients will be instructed to take letrozole at the same time each day, consistently with food or without food, and swallowed whole with a glass of water. If the patient is randomized to everolimus alone (1) or leuprolide and letrozole (2) and the cancer continues to grow, they may have the option to receive all three drugs together.
|Drug: letrozole plus leuprolide|
Experimental: Arm C combination everolimus, letrozole and leuprolide
||Drug: combination of everolimus, letrozole and leuprolide|
- 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.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01642186
|United States, California|
|University of California San Francisco|
|San Francisco, California, United States, 94143|
|United States, Maryland|
|John Hopkins Medical Center|
|Baltimore, Maryland, United States, 21287|
|United States, Massachusetts|
|Massachusetts General Hospital Cancer Center|
|Boston, Massachusetts, United States, 02114|
|Brigham and Women's Hospital|
|Boston, Massachusetts, United States, 02115|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|United States, New York|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|Principal Investigator:||Ghassan Abou-Alfa, MD||Memorial Sloan Kettering Cancer Center|