A Safety, Tolerability, and Pharmacokinetics Study of Onartuzumab as Single Agent or in Combination With Sorafenib in Participants With Advanced Hepatocellular Carcinoma

Roche

Status and phase

Completed

Phase 1

Conditions

Carcinoma, Hepatocellular

Treatments

Drug: Onartuzumab

Drug: Sorafenib

Study type

Interventional

Funder types

Industry

Identifiers

NCT01897038

GO28651

Details and patient eligibility

About

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.

Enrollment

9 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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