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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

Primary Purpose

Carcinoma, Hepatocellular

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Onartuzumab

Sorafenib

About this trial

This is an interventional treatment trial for Carcinoma, Hepatocellular

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Cohort 1 (Onartuzumab)

Cohorts 2/3 (Onartuzumab + Sorafenib)

Arm Description

Outcomes

Primary Outcome Measures

Number of Participants with Dose-limiting Toxicities (DLT)

Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)

Secondary Outcome Measures

Area Under the Concentration-time Curve (AUC) of Onartuzumab

Steady-state Plasma Concentrations of Sorafenib When Administered in Combination With Onartuzumab

Progression-free Survival (PFS)

Percentage of Participants With Objective Response

Duration of Response (DR)

Overall Survival (OS)

Percentage of Participants With Progression-free Survival at 4 Months (PFS4)

Number of Participants With Anti-therapeutic Antibodies (ATAs) Against Onartuzumab

Full Information

NCT ID

NCT01897038

First Posted

July 8, 2013

Last Updated

November 1, 2016

Sponsor

Hoffmann-La Roche

1. Study Identification

Unique Protocol Identification Number

NCT01897038

Brief Title

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

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 Type

Interventional

2. Study Status

Record Verification Date

November 2016

Overall Recruitment Status

Completed

Study Start Date

September 2013 (undefined)

Primary Completion Date

March 2015 (Actual)

Study Completion Date

March 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hoffmann-La Roche

4. Oversight

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Carcinoma, Hepatocellular

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Enrollment

9 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cohort 1 (Onartuzumab)

Arm Type

Experimental

Arm Title

Cohorts 2/3 (Onartuzumab + Sorafenib)

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Onartuzumab

Other Intervention Name(s)

RO5490258

Intervention Description

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).

Intervention Type

Drug

Intervention Name(s)

Sorafenib

Intervention Description

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).

Primary Outcome Measure Information:

Title

Number of Participants with Dose-limiting Toxicities (DLT)

Time Frame

Maximum up to 42 days

Title

Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)

Time Frame

Up to approximately 31 months

Secondary Outcome Measure Information:

Title

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)

Title

Steady-state Plasma Concentrations of Sorafenib When Administered in Combination With Onartuzumab

Time Frame

Day 1 Cycles 1-2

Title

Progression-free Survival (PFS)

Time Frame

Up to approximately 31 months

Title

Percentage of Participants With Objective Response

Time Frame

Up to approximately 31 months

Title

Duration of Response (DR)

Time Frame

Up to approximately 31 months

Title

Overall Survival (OS)

Time Frame

Up to approximately 31 months

Title

Percentage of Participants With Progression-free Survival at 4 Months (PFS4)

Time Frame

4 months

Title

Number of Participants With Anti-therapeutic Antibodies (ATAs) Against Onartuzumab

Time Frame

Up to approximately 31 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Trials

Organizational Affiliation

Hoffmann-La Roche

Official's Role

Study Director

Facility Information:

City

Sarasota

State/Province

Florida

ZIP/Postal Code

34232

Country

United States

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21231

Country

United States

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37203

Country

United States

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

City

Pokfulam

Country

Hong Kong

City

Singapore

ZIP/Postal Code

119228

Country

Singapore

City

Singapore

ZIP/Postal Code

169610

Country

Singapore

City

Tainan

ZIP/Postal Code

00704

Country

Taiwan

City

Taipei

ZIP/Postal Code

100

Country

Taiwan

12. IPD Sharing Statement

Learn more about this trial

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

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