a study on Liver Cancer
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).
Phase II Trial of the 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 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.
Hepatocellular Carcinoma Advanced HCC Temsirolimus TORISEL Sorafenib Everolimus Sirolimus Niacinamide
Open to people ages 18 years to 85 years
Adequate bone marrow function:
absolute neutrophil count ≥ 1,000/mcL platelets ≥ 75,000/mcL hemoglobin ≥ 8.5 g/dL
Adequate hepatic function:
total bilirubin ≤ 2 mg/dL or ≤ 1.5 times ULN AST(SGOT) & ALT (SGPT) ≤ 5 X ULN INR ≤1.5 X ULN
Adequate renal function:
albumin ≥ 2.8 g/dL creatinine ≤1. 5 X ULN
The effects of temsirolimus on the developing human fetus are unknown. For this reason and because sorafenib - also being used in this trial - is known to be teratogenic, women of child-bearing potential must have a negative pregnancy test within 14 days of study enrollment.
Also, women of child-bearing potential and men must agree to use two methods adequate contraception (hormonal plus barrier or two forms of barrier) or abstinence prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she needs to inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, or be surgically sterile, for the duration of study participation, and for 3 months after completion of study drug administration.
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