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

A Phase Ib, Open-Label Study Evaluating The Safety, Tolerability, and Pharmacokinetics of Onartuzumab Given as a Single Agent and in Combination With Sorafenib in Patients With Advanced Hepatocellular Carcinoma (HCC)

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.

Study Overview

• Status: Completed
• Conditions: Carcinoma, Hepatocellular
• Intervention / Treatment: Drug: Onartuzumab; Drug: Sorafenib

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• Hong Kong
  • Pokfulam, Hong Kong
• Singapore
  • Singapore, Singapore, 119228
  • Singapore, Singapore, 169610
• Taiwan
  • Tainan, Taiwan, 00704
  • Taipei, Taiwan, 100
• United States
  • Florida
    • Sarasota, Florida, United States, 34232
  • Maryland
    • Baltimore, Maryland, United States, 21231
  • New York
    • New York, New York, United States, 10065
  • Tennessee
    • Nashville, Tennessee, United States, 37203
  • Texas
    • Houston, Texas, United States, 77030

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 (Onartuzumab)	Drug: Onartuzumab; Onartuzumab intravenous infusion at a starting dose of 10 or 15 milligram per kilogram body weight administered every 3 weeks (Q3W) until disease progression or unacceptable toxicity occurs (maximum up to 31 months).; Other Names: RO5490258
Experimental: Cohorts 2/3 (Onartuzumab + Sorafenib)	Drug: Onartuzumab; Onartuzumab intravenous infusion at a starting dose of 10 or 15 milligram per kilogram body weight administered every 3 weeks (Q3W) until disease progression or unacceptable toxicity occurs (maximum up to 31 months).; Other Names: RO5490258; Drug: Sorafenib; Sorafenib 400 milligram (mg) tablets (2 tablets of 200 mg each) orally once daily or twice daily depending on the cohort assigned until disease progression or unacceptable toxicity occurs (maximum up to 31 months).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with Dose-limiting Toxicities (DLT)	Maximum up to 42 days
Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)	Up to approximately 31 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Area Under the Concentration-time Curve (AUC) of Onartuzumab	Day 1 up to Day 15 of Cycle 1, Day 1 of Cycle 2, 3, 4, and every fourth cycle thereafter (maximum up to 31 months)
Steady-state Plasma Concentrations of Sorafenib When Administered in Combination With Onartuzumab	Day 1 Cycles 1-2
Progression-free Survival (PFS)	Up to approximately 31 months
Percentage of Participants With Objective Response	Up to approximately 31 months
Duration of Response (DR)	Up to approximately 31 months
Overall Survival (OS)	Up to approximately 31 months
Percentage of Participants With Progression-free Survival at 4 Months (PFS4)	4 months
Number of Participants With Anti-therapeutic Antibodies (ATAs) Against Onartuzumab	Up to approximately 31 months

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: July 8, 2013
• First Submitted That Met QC Criteria: July 8, 2013
• First Posted (Estimate): July 11, 2013

Study Record Updates

• Last Update Posted (Estimate): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: GO28651