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

This study has been completed.
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
First received: July 8, 2013
Last updated: November 2, 2015
Last verified: November 2015
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.

Condition Intervention Phase
Carcinoma, Hepatocellular
Drug: Onartuzumab
Drug: Sorafenib
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Number of Participants with Dose-limiting Toxicities (DLT) [ Time Frame: Maximum up to 42 days ] [ Designated as safety issue: No ]
  • Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) [ Time Frame: Up to approximately 31 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Area Under the Concentration-time Curve (AUC) of Onartuzumab [ Time Frame: 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) ] [ Designated as safety issue: No ]
  • Steady-state Plasma Concentrations of Sorafenib When Administered in Combination With Onartuzumab [ Time Frame: Day 1 Cycles 1-2 ] [ Designated as safety issue: No ]
  • Progression-free Survival (PFS) [ Time Frame: Up to approximately 31 months ] [ Designated as safety issue: No ]
  • Percentage of Participants With Objective Response [ Time Frame: Up to approximately 31 months ] [ Designated as safety issue: No ]
  • Duration of Response (DR) [ Time Frame: Up to approximately 31 months ] [ Designated as safety issue: No ]
  • Overall Survival (OS) [ Time Frame: Up to approximately 31 months ] [ Designated as safety issue: No ]
  • Percentage of Participants With Progression-free Survival at 4 Months (PFS4) [ Time Frame: 4 months ] [ Designated as safety issue: No ]
  • Number of Participants With Anti-therapeutic Antibodies (ATAs) Against Onartuzumab [ Time Frame: Up to approximately 31 months ] [ Designated as safety issue: No ]

Enrollment: 9
Study Start Date: September 2013
Study Completion Date: March 2015
Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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).


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01897038

United States, Florida
Sarasota, Florida, United States, 34232
United States, Maryland
Baltimore, Maryland, United States, 21231
United States, New York
New York, New York, United States, 10065
United States, Tennessee
Nashville, Tennessee, United States, 37203
United States, Texas
Houston, Texas, United States, 77030
Hong Kong
Pokfulam, Hong Kong
Singapore, Singapore, 119228
Singapore, Singapore, 169610
Tainan, Taiwan, 00704
Taipei, Taiwan, 100
Sponsors and Collaborators
Hoffmann-La Roche
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01897038     History of Changes
Other Study ID Numbers: GO28651
Study First Received: July 8, 2013
Last Updated: November 2, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Digestive System Diseases
Digestive System Neoplasms
Liver Diseases
Liver Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Antibodies, Monoclonal
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2015