A Study of Atezolizumab in Combination with Bevacizumab Compared with Sorafenib in Patients with Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma
- Conditions
- ocally advanced or Metastatic hepatocellular carcinoma (HCC)MedDRA version: 21.1Level: LLTClassification code 10077738Term: Hepatocellular carcinoma metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: LLTClassification code 10019828Term: Hepatocellular carcinoma non-resectableSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10073071Term: Hepatocellular carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 24.0Level: LLTClassification code 10077736Term: Hepatocellular carcinoma stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 24.0Level: LLTClassification code 10077737Term: Hepatocellular carcinoma stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-003691-31-PL
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 558
- Age >= 18 years
- Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by histology/cytology or clinically by American Association for the Study of Liver Diseases criteria in cirrhotic patients
- Disease that is not amenable to curative surgical and/or locoregional therapies, or progressive disease after surgical and /or locoregional therapies
- No prior systemic therapy (including systemic investigational agents) for HCC
- At least 1 measurable (per RECIST 1.1) untreated lesion
- Patients who received prior local therapy are eligible provided the target lesion(s) have not been previously treated with local therapy or the target lesion(s) within the field of local therapy have subsequently progressed in accordance with RECIST v1.1
- Pre-treatment tumor tissue sample (if available)
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 within 7 days prior to randomization
- Child-Pugh class A within 7 days prior to randomization
- Adequate hematologic and end-organ function
- Resolution of any acute, clinically significant treatment-related toxicity from prior therapy to Grade <= 1 prior to study entry, with the exception of alopecia
- Negative HIV test at screening
- Documented virology status of hepatitis, as confirmed by screening HBV and HCV serology test
- For patients with active hepatitis B virus, HBV DNA 500 IU/mL obtained within 28 days prior to initiation of study treatment and anti-HBV treatment (per local standard of care; e.g., entecavir) for a minimum of 14 days prior to study entry and willingness to continue treatment for the length of the study
- For women of childbearing potential: agreement to remain abstinent or use contraceptive methods with a failure rate of < 1% per year during
the treatment period and for at least 5 months after the last dose of atezolizumab, 6 months after the last dose of bevacizumab, or 6 months
after the last dose of sorafenib. Women must refrain from donating eggs during this same period.
- For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm during the treatment period and for 6 months after the last dose of bevacizumab or 3 months after the last dose of sorafenib
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 258
- History of leptomeningeal disease, idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan
- Active or history of autoimmune disease or immune deficiency,
- Known active tuberculosis, moderate or severe ascites
- Significant cardiovascular disease within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
- History of congenital long QT syndrome, or corrected QT interval > 500 ms at screening and uncorrectable electrolyte disorder affecting serum level of potassium, calcium, or magnesium
- Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major
surgical procedure during the study
- History of malignancy other than HCC within 5 years prior to screening,
apart from malignancies with a negligible risk of metastasis or death and hepatic encephalopathy
-Severe infection within 4 weeks prior to initiation of study treatment, or any active infection that, in the opinion of the investigator, could impact patient safety
- Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment, a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the last dose of atezolizumab
- Prior allogeneic stem cell or solid organ transplantation, Prior treatment with CD137 agonists or immune checkpoint blockade
therapies, including anti- cytotoxic T-lymphocyte-associated protein 4, anti- Programmed death (PD)-1, and anti-PD-Ligand 1 therapeutic antibodies
- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
- Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab or bevacizumab formulation
- Fibrolamellar and sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
- Pregnant or breastfeeding, or intention of becoming pregnant during study treatment or within at least 5 months after the last dose of
atezolizumab, 6 months after the last dose of bevacizumab, or 6 months after the last dose of sorafenib
- Patients with untreated or incompletely treated esophageal and/or
gastric varices with bleeding or high-risk for bleeding
- A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment
- Co-infection of hepatitis B and C virus
- Symptomatic, untreated, or actively progressing central nervous system metastases
- Uncontrolled tumor-related pain
- Pleural effusion, pericardial effusion, or ascites requiring recurrent
drainage procedures
- Uncontrolled or symptomatic hypercalcemia
- Treatment with investigational therapy within 28 days prior to study treatment
- Strong CYP3A4 inducers within 14 days prior to study treatment
- Systemic immunostimulatory agents and immunosuppressive
medication within 4 weeks or 5 half-lives of the drug and 2 weeks prior to initiation of study treatment, or anticipation of need for systemic
immunosuppressive medication during study
- Inadequately controlled arterial hypertensi
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method