A Randomized Controlled Phase 2 Trial of ARQ 197 in Patients with Unresectable Hepatocellular Carcinoma (HCC) Who Have Failed One Prior Systemic Therapy - ND

INTERVENTION: Product Name: ARQ 197 Product Code: ARQ 197 Pharmaceutical Form: Capsule, hard Current Sponsor code: AQ 3227197 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 360‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use CONDITION: Unresectable Hepatocellular Carcinoma (HCC) ; MedDRA version: 9.1 Level: LLT Classification code 10019828 PRIMARY OUTCOME: Main Objective: Evaluate time to progression (TTP) among all patients treated with ARQ 197 compared to placebo. Primary end point(s): TTP is the primary endpoint. Secondary Objective:  Evaluate progression‐free survival (PFS), overall survival (OS), objective response rate (ORR) and disease control rate among all patients treated with ARQ 197 compared to placebo.  Evaluate ORR in crossover population following radiographic disease progression on placebo.  Further characterize the safety of ARQ 197 in patients with unresectable HCC.  Further evaluate pharmacokinetics of ARQ 197 INCLUSION CRITERIA: Each prospective subject must meet ALL of the following inclusion criteria in order to be eligible for this study: 1. Written informed consent granted prior to initiation of any study‐specific screening procedures 2. 18 year of age or older 3. Histologically or cytologically confirmed HCC 4. Archival, fresh core needle biopsy or fine needle aspiration (FNA) tumor samples 5. Received at least one cycle of prior systemic therapy (at least 3 weeks for continuously administered drugs) and experienced radiographic disease progression or was unable to tolerate therapy. 6. Discontinued prior treatment for at least 4 weeks, or at least 2 weeks (14 days) if drug was administered continuously and orally (e.g. sorafenib or sunitinib), prior to the study randomization 7. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤1 (Appendix 2) 8. Local or loco‐regional therapy (i.e., surgery, radiation therapy, hepatic arterial embolization, chem