a safety, tolerability, and pharmacokinetics study of onartuzumab as single agent or in combination with sorafenib in participants with advanced hepatocellular carcinoma

Conditions: Carcinoma, Hepatocellular

Summary: this multicenter, open-label study will evaluate the maximum tolerated dose (mtd) and dose-limiting toxicities of onartuzumab as single agent or in combination with sorafenib in participants with advanced hepatocellular carcinoma. participants in cohort 1 will receive onartuzumab as single agent on day 1 of each 21-day cycle. participants in cohorts 2 or 3 will receive onartuzumab on day 1 of each 21-day cycle in combination with sorafenib 400 mg orally daily or twice daily. anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.


Eligibility criteria:
inclusion criteria: * eastern cooperative oncology group (ecog) performance status of 0 or 1 * cytologically or histologically confirmed diagnosis of hepatocellular carcinoma (hcc) * advanced or metastatic disease * not a candidate for curative treatments (that is, resection, transplantation) * child-pugh class a liver function * measurable disease as defined by response evaluation criteria in solid tumors (recist) version 1.1 * life expectancy greater than (\>) 3 months * for participants who received prior adjuvant chemotherapy, a treatment-free interval of at least 6 months between the last chemotherapy cycle and cycle 1 day 1 exclusion criteria: * prior surgery or local therapy within 4 weeks prior to cycle 1 day 1, with the exception of palliative radiation therapy to the bone * brain metastasis or spinal cord compression not definitively treated with surgery and/or radiation * granulocyte count less than (\<) 1500 per cubic millimeter (mm\^3), platelet count \< 75,000/mm\^3, and hemoglobin \< 8 gram per deciliter (g/dl) within 7 days prior to cycle 1 day 1 * total bilirubin greater than (\>) 1.5 times the upper limit of normal (uln) * aspartate aminotransferase (ast) serum glutamic-oxaloacetic transaminase (sgot), alanine transaminase (alt) serum glutamic-pyruvic transaminase (sgpt), alkaline phosphatase (alp) \> 5 × uln * serum creatinine \> 1.5 × uln or creatinine clearance \< 60 cubic centimeter per minute (cc/min) by cockcroft-gault formula * significant history of cardiac disease within 6 months prior to cycle 1 day 1, myocardial infarction within the previous year, or current cardiac ventricular arrhythmias requiring medication * serious active infection, or other serious underlying medical conditions that would impair the ability of the participant to receive protocol treatment, with the exception of hepatitis b virus (hbv) and hepatitis c virus (hcv) infections * known active infection with human immunodeficiency virus (hiv) or known hiv-seropositivity * inability to take oral medication or untreated malabsorption syndrome * pregnant or lactating women * history of transplantation including organ, bone marrow transplantation, and peripheral blood stem cell transplantation with the exception of corneal transplantation * active bleeding diathesis (including active esophageal varices) or tumor rupture within 8 weeks prior to cycle 1 day1 that are not successfully treated * uncontrolled hypertension * treatment with any other investigational drug within 4 weeks of cycle 1 day