Carcinoma, HepatocellularPhase 1NCT01897038
A Safety, Tolerability, and Pharmacokinetics Study of Onartuzumab as Single Agent or in Combination With Sorafenib in Participants With Advanced Hepatocellular Carcinoma
A Phase 1 study testing Onartuzumab and Sorafenib in people with Carcinoma, Hepatocellular, run by Hoffmann-La Roche at 10 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Hepatocellular
- What is being tested?
- Onartuzumab and Sorafenib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 10 sitesin 4 countries
- Study dates
- Sep 2013to Mar 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
10 sites in 4 countries.
10 sites in 4 countries
United States5 sites
Study site
Baltimore, Maryland, 21231
Study site
Houston, Texas, 77030
Study site
Nashville, Tennessee, 37203
Study site
New York, New York, 10065
Study site
Sarasota, Florida, 34232
About this study
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)
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.
- Conditions
- Carcinoma, Hepatocellular
- Being tested
- Onartuzumab, Sorafenib
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OnartuzumabDrug
Also called RO5490258
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).
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).
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 (Onartuzumab) | Experimental | Not described Receives: Drug: Onartuzumab |
| Cohorts 2/3 (Onartuzumab + Sorafenib) | Experimental | Not described Receives: Drug: Onartuzumab; Drug: Sorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Dose-limiting Toxicities (DLT)
Measured: Maximum up to 42 days
Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)
Measured: Up to approximately 31 months
Secondary outcomes (8)
Area Under the Concentration-time Curve (AUC) of Onartuzumab
Measured: 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
Measured: Day 1 Cycles 1-2
Progression-free Survival (PFS)
Measured: Up to approximately 31 months
Percentage of Participants With Objective Response
Measured: Up to approximately 31 months
Duration of Response (DR)
Measured: Up to approximately 31 months
Overall Survival (OS)
Measured: Up to approximately 31 months
Percentage of Participants With Progression-free Survival at 4 Months (PFS4)
Measured: 4 months
Number of Participants With Anti-therapeutic Antibodies (ATAs) Against Onartuzumab
Measured: Up to approximately 31 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2013 (estimated)
- Study startSep 2013
- Primary completionMar 2015
- Study completionMar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, HepatocellularStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01897038
- Sponsor's protocol ID
- GO28651
- Status last verified
- Nov 2016
- First submitted
- 8 Jul 2013
- Last updated
- 2 Nov 2016
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01897038
- Acronym / sponsor ID
- GO28651
- Conditions
- Carcinoma, Hepatocellular
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- Sep 2013
- Primary completion
- Mar 2015 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 11 Jul 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 (Onartuzumab) | Experimental | Drug: Onartuzumab |
| Cohorts 2/3 (Onartuzumab + Sorafenib) | Experimental | Drug: Onartuzumab, Drug: Sorafenib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OnartuzumabAlso: RO5490258Onartuzumab 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). | Drug | Cohort 1 (Onartuzumab), Cohorts 2/3 (Onartuzumab + Sorafenib) |
| SorafenibSorafenib 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). | Drug | Cohorts 2/3 (Onartuzumab + Sorafenib) |
Primary outcome
Number of Participants with Dose-limiting Toxicities (DLT)
Time frame: Maximum up to 42 days
Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)
Time frame: Up to approximately 31 months
8 secondary outcomes
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)
Steady-state Plasma Concentrations of Sorafenib When Administered in Combination With Onartuzumab
Time frame: Day 1 Cycles 1-2
Progression-free Survival (PFS)
Time frame: Up to approximately 31 months
Percentage of Participants With Objective Response
Time frame: Up to approximately 31 months
Duration of Response (DR)
Time frame: Up to approximately 31 months
Overall Survival (OS)
Time frame: Up to approximately 31 months
Percentage of Participants With Progression-free Survival at 4 Months (PFS4)
Time frame: 4 months
Number of Participants With Anti-therapeutic Antibodies (ATAs) Against Onartuzumab
Time frame: Up to approximately 31 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
10 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Onartuzumab and Sorafenib in people with Carcinoma, Hepatocellular, run by Hoffmann-La Roche at 10 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, Singapore, Taiwan, Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with Dose-limiting Toxicities (DLT) (time frame: Maximum up to 42 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2016.