A Study of Onartuzumab as Single Agent and in Combination With Sorafenib in Patients With Advanced Hepatocellular Carcinoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01897038
First received: July 8, 2013
Last updated: July 7, 2014
Last verified: July 2014
  Purpose

This multicenter, open-label study will evaluate the maximum tolerated dose (MTD

) and dose-limiting toxicities of onartuzumab as single agent and in combination with sorafenib in patients with advanced hepatocellular carcinoma. Patients in Cohort 1 will receive onartuzumab as single agent on Day 1 of each 21-day cycle.

Patients in Cohorts 2 and 3 will receive onartuzumab on Day 1 of each 21-day cy cle in combination with sorafenib 400 mg orally daily or twice daily. Anticipate d time on study treatment is until disease progression or unacceptable toxicity occurs.


Condition Intervention Phase
Liver Cancer
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:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 54
Study Start Date: September 2013
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1 Drug: onartuzumab
Multiple doses
Experimental: Cohorts 2/3 Drug: onartuzumab
Multiple doses
Drug: sorafenib
400 mg QD or BID

  Eligibility

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

Inclusion Criteria:

  • Adult patients, >/= 18 years of age
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Cytologically or histologically confirmed diagnosis of hepatocellular carcinoma (HCC)
  • Advanced or metastatic disease
  • Child-Pugh class A liver function
  • Measurable disease as defined by RECIST 1.1

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 < 1500/mm3, platelet count < 75,000/ mm3, and hemoglobin < 8 g/dL within 7 days prior to Cycle 1 Day 1
  • Total bilirubin > 1.5 ×ULN
  • AST (SGOT), ALT (SGPT), alkaline phosphatase (ALP) > 5 ×ULN
  • Serum creatinine > 1.5 × ULN or creatinine clearance < 60 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 patient to receive protocol treatment, with the exception of HBV and 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) 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 1
  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

Contacts
Contact: Reference Study ID Number: GO28651 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. Only) global.rochegenentechtrials@roche.com

Locations
United States, Florida
Recruiting
Sarasota, Florida, United States, 34232
United States, Maryland
Recruiting
Baltimore, Maryland, United States, 21231
United States, New York
Recruiting
New York, New York, United States, 10065
United States, Tennessee
Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
Recruiting
Houston, Texas, United States, 77030
Hong Kong
Recruiting
Pokfulam, Hong Kong
Singapore
Recruiting
Singapore, Singapore, 169610
Recruiting
Singapore, Singapore, 119228
Taiwan
Active, not recruiting
Tainan, Taiwan, 00704
Recruiting
Taipei, Taiwan, 100
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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: July 7, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Liver Neoplasms
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Adenocarcinoma
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 24, 2014