Clinical trial NCT01897038: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Carcinoma, Hepatocellular
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2013-07-11
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of Participants with Dose-limiting Toxicities (DLT)
timeFrame: Maximum up to 42 days
measure: Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)
timeFrame: Up to approximately 31 months
Secondary outcomes:
measure: Area Under the Concentration-time Curve (AUC) of Onartuzumab
timeFrame: 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)
measure: Steady-state Plasma Concentrations of Sorafenib When Administered in Combination With Onartuzumab
timeFrame: Day 1 Cycles 1-2
measure: Progression-free Survival (PFS)
timeFrame: Up to approximately 31 months
measure: Percentage of Participants With Objective Response
timeFrame: Up to approximately 31 months
measure: Duration of Response (DR)
timeFrame: Up to approximately 31 months
measure: Overall Survival (OS)
timeFrame: Up to approximately 31 months
measure: Percentage of Participants With Progression-free Survival at 4 Months (PFS4)
timeFrame: 4 months
measure: Number of Participants With Anti-therapeutic Antibodies (ATAs) Against Onartuzumab
timeFrame: Up to approximately 31 months
Other outcomes:
Locations:
city: Sarasota
country: United States
state: Florida
city: Baltimore
country: United States
state: Maryland
city: New York
country: United States
state: New York
city: Nashville
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
city: Pokfulam
country: Hong Kong
city: Singapore
country: Singapore
city: Singapore
country: Singapore
city: Tainan
country: Taiwan
city: Taipei
country: Taiwan
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: