A Safety, Tolerability, and Pharmacokinetics Study of Onartuzumab as Single Agent or in Combination With Sorafenib in Participants With Advanced Hepatocellular Carcinoma
Status: | Completed |
---|---|
Conditions: | Liver Cancer, Liver Cancer, Cancer, Cancer |
Therapuetic Areas: | Oncology |
Healthy: | No |
Age Range: | 18 - Any |
Updated: | 8/3/2016 |
Start Date: | September 2013 |
End Date: | March 2015 |
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)
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.
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.
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
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