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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.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01897038
First received: July 8, 2013
Last updated: November 1, 2016
Last verified: November 2016

July 8, 2013
November 1, 2016
September 2013
March 2015   (final data collection date for primary outcome measure)
  • 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 ]
  • Incidence and nature of dose-limiting toxicities (DLTs) [ Time Frame: up to 42 days ] [ Designated as safety issue: Yes ]
  • Incidence, nature and severity of adverse events, graded according to the NCI CTCAE v4.0 [ Time Frame: Up to approximately 31 months ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01897038 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Pharmacokinetics: Area under the concentration-time curve (AUC) [ Time Frame: 15 days ] [ Designated as safety issue: No ]
  • Steady-state plasma sorafenib concentrations when administered in combination with onartuzumab [ Time Frame: Day 1 Cycles 1-4 ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: Up to approximately 31 months ] [ Designated as safety issue: No ]
  • Objective response rate [ Time Frame: Up to approximately 31 months ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: Up to approximately 31 months ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to approximately 31 months ] [ Designated as safety issue: No ]
  • Progression-free survival at 4 months [ Time Frame: 4 months ] [ Designated as safety issue: No ]
  • Incidence of anti-therapeutic antibodies (ATAs) against onartuzumab [ Time Frame: Up to approximately 31 months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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.
Not Provided
Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Carcinoma, Hepatocellular
  • 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).
  • Experimental: Cohort 1 (Onartuzumab)
    Intervention: Drug: Onartuzumab
  • Experimental: Cohorts 2/3 (Onartuzumab + Sorafenib)
    Interventions:
    • Drug: Onartuzumab
    • Drug: Sorafenib
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
9
March 2015
March 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Hong Kong,   Singapore,   Taiwan
 
NCT01897038
GO28651
Not Provided
Not Provided
Not Provided
Hoffmann-La Roche
Hoffmann-La Roche
Not Provided
Study Director: Clinical Trials Hoffmann-La Roche
Hoffmann-La Roche
November 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP