Phase II Combination of Temsirolimus and Sorafenib in Advanced Hepatocellular Carcinoma

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.