NCT01897038

Brief Summary

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
9

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Sep 2013

Geographic Reach
4 countries

10 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 8, 2013

Completed
3 days until next milestone

First Posted

Study publicly available on registry

July 11, 2013

Completed
2 months until next milestone

Study Start

First participant enrolled

September 1, 2013

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2015

Completed
Last Updated

November 2, 2016

Status Verified

November 1, 2016

Enrollment Period

1.5 years

First QC Date

July 8, 2013

Last Update Submit

November 1, 2016

Conditions

Carcinoma, Hepatocellular

Outcome Measures

Primary Outcomes (2)

  • 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 Outcomes (8)

  • 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

  • +3 more secondary outcomes

Study Arms (2)

Cohort 1 (Onartuzumab)

EXPERIMENTAL
Drug: Onartuzumab

Cohorts 2/3 (Onartuzumab + Sorafenib)

EXPERIMENTAL
Drug: OnartuzumabDrug: Sorafenib

Interventions

OnartuzumabDRUG

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).

Also known as: RO5490258
Cohort 1 (Onartuzumab)Cohorts 2/3 (Onartuzumab + Sorafenib)
SorafenibDRUG

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).

Cohorts 2/3 (Onartuzumab + Sorafenib)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

Unknown Facility

Sarasota, Florida, 34232, United States

Location

Unknown Facility

Baltimore, Maryland, 21231, United States

Location

Unknown Facility

New York, New York, 10065, United States

Location

Unknown Facility

Nashville, Tennessee, 37203, United States

Location

Unknown Facility

Houston, Texas, 77030, United States

Location

Unknown Facility

Pokfulam, Hong Kong

Location

Unknown Facility

Singapore, 119228, Singapore

Location

Unknown Facility

Singapore, 169610, Singapore

Location

Unknown Facility

Tainan, 00704, Taiwan

Location

Unknown Facility

Taipei, 100, Taiwan

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

onartuzumabSorafenib

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsLiver NeoplasmsDigestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesLiver Diseases

Intervention Hierarchy (Ancestors)

Phenylurea CompoundsUreaAmidesOrganic ChemicalsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsNiacinamideNicotinic AcidsAcids, HeterocyclicHeterocyclic CompoundsPyridinesHeterocyclic Compounds, 1-Ring

Study Officials

  • Clinical Trials

    Hoffmann-La Roche

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 8, 2013

First Posted

July 11, 2013

Study Start

September 1, 2013

Primary Completion

March 1, 2015

Study Completion

March 1, 2015

Last Updated

November 2, 2016

Record last verified: 2016-11

Locations

SG(2)US(5)HK(1)TW(2)