Phase II Combination of Temsirolimus and Sorafenib in Advanced Hepatocellular Carcinoma
- Registration Number
- NCT01687673
- Lead Sponsor
- University of California, San Francisco
- Brief Summary
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).
- Detailed Description
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 Hepatocellular carcinoma (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 mammalian target of rapamycin (mTOR) inhibition. Circulating biomarker data including enumeration of circulating tumor cells (CTC) and measurement of the tumor marker Alpha-fetoprotein (AFP) will be performed at specific time points 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 29
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment Temsirolimus Combination temsirolimus plus sorafenib
- Primary Outcome Measures
Name Time Method Median Time to Progression (TTP) 24 months Median TTP will be calculated in months from date of first dose of protocol therapy to date of removal from study for progression, where progression is defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as at least a 20% increase in the sum of the longest diameter of the target lesions (SLD), taking as reference the smallest sum of the SLD recorded since the treatment started and minimum 5 millimeter (mm) increase over the nadir, or the appearance of one or more new lesions for target lesions and/or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions . Kaplan-Meier methods will be used to summarize the primary endpoint
- Secondary Outcome Measures
Name Time Method Median Progression Free Survival (PFS) 24 months 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, where progression is defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as at least a 20% increase in the sum of the SLD of target lesions, taking as reference the smallest sum of the SLD recorded since the treatment started and minimum 5 millimeter (mm) increase over the nadir, or the appearance of one or more new lesions for target lesions and/or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Kaplan-Meier methods will be used to summarize time-to-event outcomes.
Response Rate (RR) 24 months Response Rate (RR) is defined as any patient whom has a documented complete response (CR) or partial response (PR) per RECIST version 1.1 criteria. Results will be reported by number of participants for each response type: CR or PR.
Number of Patients Whom Required a Dose Reduction 24 months The number of patients whom required a dose reduction due to toxicity as classified by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be reported
Median Overall Survival (OS) 60 months 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. The survival of patients still alive after 5 years of follow up post study discontinuation will be censored.
Number of Participants Whom Discontinued Treatment Due to Intolerable Toxicity 24 months The number of participants whom discontinued treatment due to toxicity as classified by the CTCAE version 4.0 will be reported
Number of Patients With a Demonstrated Alpha-fetoprotein (AFP) Response 24 months 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 number of participants with ≥ 50% decline from baseline will be measured.
Number of Patients Whom Required a Treatment Delay 24 months The number of patients whom required a treatment delay due to toxicity as classified by the CTCAE version 4.0 will be reported
Time to Treatment Failure (TTF) 24 months TTF will be measured from date of first dose of protocol therapy to date of study discontinuation for progression, death, or toxicity.
Trial Locations
- Locations (2)
University of California, San Francisco
🇺🇸San Francisco, California, United States
Robert H Lurie Comprehensive Cancer Center
🇺🇸Chicago, Illinois, United States