Phase II Combination of Temsirolimus and Sorafenib in Advanced Hepatocellular Carcinoma
This Phase II trial is being developed following the completion of a Phase I study of the combination of temsirolimus and sorafenib in 25 first-line therapy patients with advanced hepatocellular carcinoma (December 2009 through April 2012). The maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of the combination of temsirolimus is 10 mg IV weekly plus sorafenib 200 mg (oral, twice daily).
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Trial of the Combination of Temsirolimus and Sorafenib in Advanced Hepatocellular Carcinoma|
- Median time to progression (TTP) [ Time Frame: 24 months ] [ Designated as safety issue: No ]Median TTP will be calculated in months from date of first dose of protocol therapy to date of removal from study for progression; Kaplan-Meier methods will be used to summarize the primary endpoint (median TTP).
- Response rate (RR) [ Time Frame: 24 months ] [ Designated as safety issue: No ]Response rate (RR) will be measured by RECIST version 1.1; measurements will be presented descriptively for the study cohort.
- Progression free survival (PFS) [ Time Frame: 24 months ] [ Designated as safety issue: No ]Median PFS will be calculated in months from date of first dose of protocol therapy to date of documented disease progression or death from any cause. Kaplan-Meier methods will be used to summarize time-to-event outcomes including the primary endpoint (median TTP) and secondary endpoints (PFS, TTF, OS).
- Overall survival (OS) [ Time Frame: 24 months ] [ Designated as safety issue: No ]Median OS for all enrolled patients (intention-to-treat) will be calculated from date of first dose of protocol therapy until date of death, using chart review and/or follow up phone calls to determine date of death in patients after removal from study.
- Time to treatment failure (TTF) [ Time Frame: 24 months ] [ Designated as safety issue: No ]TTF will be measured from date of first dose of protocol therapy to date of study discontinuation for progression, death, or toxicity.
- Toxicity & tolerability [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]In patients with baseline AFP ≥ 20 ng/mL, AFP response will be measured by the percent change from baseline value to the value at the time of best AFP response. The change in AFP will also be examined for association with absolute TTP and best response.
|Study Start Date:||September 2012|
|Estimated Study Completion Date:||December 2018|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Combination temsirolimus plus sorafenib
10 mg weekly will be administered intravenously over 30 to 60 minutes using an infusion pump starting on Cycle 1, Day 1 of study enrollment.Drug: Sorafenib:
200 mg tablet twice daily starting on Cycle 1, Day 1 of study enrollment after completion of temsirolimus infusion.
The hypothesis of this single-arm phase II study is that the combination of temsirolimus and sorafenib will achieve a clinically-meaningful median time to progression (TTP) of at least 6 months, with null hypothesis of less than or equal to 3 months, in first-line systemic therapy for patients with advanced HCC. A randomized trial would be required to formally compare the efficacy of this combination to sorafenib alone and will be indicated if this phase II study achieves a median TTP of at least 6 months. An interim safety analysis will employ stopping rules after 30% of planned patients have been treated with at least one dose of protocol therapy to ensure the combination does not confer excessive toxicity.
A key aspect of this study will be the requirement of histologic confirmation along with adequate archival tissue for correlative tissue analyses to explore new biomarkers of response to mTOR inhibition. Circulating biomarker data including enumeration of circulating tumor cells (CTC) and measurement of the tumor marker AFP will be performed at specific timepoints to evaluate for predictive value. Specimen banking of tissue, serum, and peripheral blood mononuclear cells will be undertaken to enable future novel biomarker studies. Modified RECIST will be performed in addition to standard RECIST 1.1 to explore for improved imaging predictors of response.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01687673
|Contact: Kate Kelley, MDfirstname.lastname@example.org|
|Contact: Jennifer Luan||415-514-6220||Jennifer.Luan@ucsf.edu|
|United States, California|
|University of California, San Francisco||Recruiting|
|San Francisco, California, United States, 94143|
|Contact: Kate Kelley, MD 415-353-9888 email@example.com|
|Contact: Blake Rosenthal 415-514-5633 Blake.Rosenthal@ucsf.edu|
|Sub-Investigator: Chloe E Atreya, MD, PhD|
|Sub-Investigator: Emily K Bergsland, MD|
|Sub-Investigator: Michael Korn, MD, PhD|
|Sub-Investigator: Andrew H Ko, MD|
|Sub-Investigator: Katherine Van Loon, MD|
|Sub-Investigator: Alan P Venook, MD|
|Sub-Investigator: Thomas Eaton Weber, NP|
|United States, Illinois|
|Robert H Lurie Comprehensive Cancer Center||Recruiting|
|Chicago, Illinois, United States, 60611|
|Contact: Erin Alonso, CCRC 312-695-4168 firstname.lastname@example.org|
|Principal Investigator: Halla Nimeiri, M.D.|
|Study Chair:||Kate Kelley, MD||University of California, San Francisco|
|Principal Investigator:||Kate Kelley, MD||University of California, San Francisco|