Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Carcinoma

Carcinoma, Hepatocellular

Liver Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Fibrolamellar Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Reproductive Control Agents

Anti-Infective Agents

Everolimus

Letrozole

Estrogens

Leuprolide

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

Aromatase Inhibitors

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Everolimus will be administered at the following doses:

* Patients with a BSA ≤ 1.5 m2 will receive everolimus 5 mg PO QD.
* Patients with a BSA \> than or = to 1.5 m2 will receive everolimus 7.5 mg PO QD. 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.

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.

* Patients with a BSA ≤ 1.5 m2 will receive everolimus 5 mg PO QD.
* Patients with a BSA \> than or = to 1.5 m2 will receive everolimus 7.5 mg PO QD. Leuprolide 7.5 mg IM will be given every 4 weeks (+/- 7 days). Everolimus and letrozole will be administered continuously using the same dose, schedule and administration. Everolimus, letrozole and leuprolide should be administered concurrently at all times.

everolimus

letrozole plus leuprolide

combination of everolimus, letrozole and leuprolide

Ghassan Abou-Alfa, MD

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.

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)

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)

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.

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.

Kaplan-Meier OS will be measured from the date that study therapy was commenced until the date of death.

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. Stable Disease is defined as neither sufficient shrinkage (compared to baseline) to qualify for Partial Reponse nor sufficient increase (taking as reference the smallest sum diameters while on study) to qualify for Progressive Disease.

Adverse events/toxicity will be monitored and recorded using the CTCAE version 4.0 and summarized descriptively.

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.

The Fibrolamellar Cancer Foundation

Dana-Farber Cancer Institute/Brigham and Women¹s Cancer Center and Massachusetts General Hospital Cancer Center

Johns Hopkins University

University of California, San Francisco

Abbott

Novartis Pharmaceuticals

Memorial Sloan Kettering Cancer Center

Everolimus will be administered at the following doses:

* Patients with a BSA ≤ 1.5 m2 will receive everolimus 5 mg PO QD.
* Patients with a BSA \> than or = to 1.5 m2 will receive everolimus 7.5 mg PO QD. 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.

everolimus

Arm A Everolimus

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.

letrozole plus leuprolide

Arm B Letrozole Plus Leuprolide

* Patients with a BSA ≤ 1.5 m2 will receive everolimus 5 mg PO QD.
* Patients with a BSA \> than or = to 1.5 m2 will receive everolimus 7.5 mg PO QD. Leuprolide 7.5 mg IM will be given every 4 weeks (+/- 7 days). Everolimus and letrozole will be administered continuously using the same dose, schedule and administration. Everolimus, letrozole and leuprolide should be administered concurrently at all times.

combination of everolimus, letrozole and leuprolide

Arm C Combination Everolimus, Letrozole and Leuprolide

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Ghassan Abou-Alfa, MD

Efficacy Endpoints for Part 1 of the Study is Progression-free Survival at 6 Months (PFS6)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
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)	NCT01642186	Fibrolamellar C... Fibrolamellar L...	everolimus letrozole plus ... combination of ...	12 Years -	Memorial Sloan Kettering Cancer Center
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)	NCT01642186	Fibrolamellar C... Fibrolamellar L...	everolimus letrozole plus ... combination of ...	12 Years -	Memorial Sloan Kettering Cancer Center

Spots Global Cancer Trial Database for letrozole plus leuprolide