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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

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT01897038
Collaborator
(none)
9
Enrollment
10
Locations
2
Arms
17.9
Duration (Months)
0.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
9 participants
Intervention Model:
Parallel Assignment
Masking:
None (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)
Study Start Date :
Sep 1, 2013
Actual Primary Completion Date :
Mar 1, 2015
Actual Study Completion Date :
Mar 1, 2015

Arms and Interventions

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).

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants with Dose-limiting Toxicities (DLT) [Maximum up to 42 days]

    2. Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) [Up to approximately 31 months]

    Secondary Outcome Measures

    1. 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)]

    2. Steady-state Plasma Concentrations of Sorafenib When Administered in Combination With Onartuzumab [Day 1 Cycles 1-2]

    3. Progression-free Survival (PFS) [Up to approximately 31 months]

    4. Percentage of Participants With Objective Response [Up to approximately 31 months]

    5. Duration of Response (DR) [Up to approximately 31 months]

    6. Overall Survival (OS) [Up to approximately 31 months]

    7. Percentage of Participants With Progression-free Survival at 4 Months (PFS4) [4 months]

    8. Number of Participants With Anti-therapeutic Antibodies (ATAs) Against Onartuzumab [Up to approximately 31 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    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 (mm3), platelet count < 75,000/mm3, 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

    Locations

    Site City State Country Postal Code
    1 Sarasota Florida United States 34232
    2 Baltimore Maryland United States 21231
    3 New York New York United States 10065
    4 Nashville Tennessee United States 37203
    5 Houston Texas United States 77030
    6 Pokfulam Hong Kong
    7 Singapore Singapore 119228
    8 Singapore Singapore 169610
    9 Tainan Taiwan 00704
    10 Taipei Taiwan 100

    Sponsors and Collaborators

    • Hoffmann-La Roche

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT01897038
    Other Study ID Numbers:
    • GO28651
    First Posted:
    Jul 11, 2013
    Last Update Posted:
    Nov 2, 2016
    Last Verified:
    Nov 1, 2016
    Additional relevant MeSH terms:
    Carcinoma
    Carcinoma, Hepatocellular
    Sorafenib

    Study Results

    No Results Posted as of Nov 2, 2016