Phase I trial of temsirolimus (TEM) plus sorafenib (SOR) in advanced hepatocellular carcinoma (HCC).

296 Background: SOR prolongs survival in patients (pts) with HCC. In preclinical studies, mammalian target of rapamycin (mTOR) inhibitors (I) impair HCC growth and angiogenesis. Adding mTOR-I to SOR augments antitumor effect. Phase I studies of mTOR-I plus SOR have shown tolerability but did not include cirrhotic pts. We developed a phase I trial of mTOR-I TEM plus SOR to determine safety, maximum tolerated dose (MTD), and recommended phase II dose (RP2D) in pts with HCC. The study was approved and funded by the National Comprehensive Cancer Network (NCCN). Methods: Eligibility: Advanced HCC diagnosed histologically or clinically. No prior systemic therapy (Tx). Prior resection/local Tx permitted if ≥1 measurable site. ECOG score ≤2, Child-Pugh ≤7, bilirubin ≤2 mg/dL, platelets ≥75,000/mcL. Design: 3+3 escalation to MTD with dose-limiting toxicity (DLT) window 28 days; 6 pts at MTD for pharmacokinetics (PK). Endpoints: 1°: MTD, RP2D. 2°: Safety, toxicity, PK. Results: 9 pts enrolled to date: 7 at DL1, 2 a...