Efficacy Endpoints for Part 1 of the Study is Progression-free Survival at 6 Months (PFS6)
| Group | Value (Participants) |
|---|---|
| Arm A Everolimus | 0 |
| Arm B Letrozole Plus Leuprolide | 0 |
| Arm C Combination Everolimus, Letrozole and Leuprolide | 0 |
Trial · Interventional
CompletedPhase 2Results postedRegistry dataUnited States
1 trial · 1 completed · 1 with posted results
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)
NCT0164218612 Jul 2012 to 16 Jul 2021
Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.
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.
Experimental
Arm A everolimus
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.
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.
Experimental
Arm C combination everolimus, letrozole and 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.
Outcomes the sponsor listed as primary.
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 · From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Kaplan-Meier OS will be measured from the date that study therapy was commenced until the date of death.
Percentage of Participants With Stable Disease
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. 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.
Number of Participants With One or More Adverse Events/Toxicity
Time frame · 2 years
Adverse events/toxicity will be monitored and recorded using the CTCAE version 4.0 and summarized descriptively.
Number of Participants With Tissue Biomarkers Collected
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.
Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.
| Group | Value (Participants) |
|---|---|
| Arm A Everolimus | 0 |
| Arm B Letrozole Plus Leuprolide | 0 |
| Arm C Combination Everolimus, Letrozole and Leuprolide | 0 |
| Group | Value (months) |
|---|---|
| Arm A Everolimus | 2.6 |
| Arm B Letrozole Plus Leuprolide | 2.7 |
| Arm C Combination Everolimus, Letrozole and Leuprolide | 2.4 |
| Group | Value (months) |
|---|---|
| Arm A Everolimus | 12.5 |
| Arm B Letrozole Plus Leuprolide | 14.0 |
| Arm C Combination Everolimus, Letrozole and Leuprolide | 10.6 |
| Group | Value (Percentage of pts with stable disease) |
|---|---|
| Arm A Everolimus | 55 |
| Arm B Letrozole Plus Leuprolide | 37 |
| Arm C Combination Everolimus, Letrozole and Leuprolide | 11 |
| Group | Value (Participants) |
|---|---|
| Arm A Everolimus | 9 |
| Arm B Letrozole Plus Leuprolide | 9 |
| Arm C Combination Everolimus, Letrozole and Leuprolide | 10 |
| Group | Value (Participants) |
|---|---|
| Arm A Everolimus | 9 |
| Arm B Letrozole Plus Leuprolide | 9 |
| Arm C Combination Everolimus, Letrozole and Leuprolide | 10 |
| Group | Deaths | Serious events | Other events |
|---|---|---|---|
| Arm A EverolimusEverolimus 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 | 0 / 9 | 0 / 9 | 9 / 9 |
| Arm B Letrozole Plus LeuprolideDay 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 | 2 / 9 | 0 / 9 | 9 / 9 |
| Arm C Combination Everolimus, Letrozole and 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 | 2 / 10 | 0 / 10 | 9 / 10 |
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