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: 24.0Level: LLTClassification code 10077737Term: Hepatocellular carcinoma stage IVSystem 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: 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: 21.1Level: LLTClassification code 10077738Term: Hepatocellular carcinoma metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-003691-31-IT
- Lead Sponsor
- F. HOFFMANN - LA ROCHE LTD.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- 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 one 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)
- 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 1 month 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
-H.of leptomeningeal disease, idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest TC scan
-Active/h.of autoimmune disease or immune deficiency, known active tuberculosis, moderate/severe ascites
-Sign. cardiovascular disease within 3 m prior initiation study treat, unstable arrhythmia or unstable angina
-H.of congenital long QT syndrome or corrected QT interval>500 ms at screening and uncorrectable electrolyte disorder affecting serum level of K, Ca, or Mg
-Major surgical procedure within 4w prior initiation of study treat or anticipation of need for a major surgical procedure during the study
-H.of malignancy other than HCC within 5y prior screening with the exception of malignancies with a negligible risk of metastasis or death and hepatic encephalopathy
-Treat with therapeutic oral or IV antibiotics within 2w prior initiation study treat, a live attenuated vaccine within 4w prior initiation study treat or anticipation of need for such a vaccine during atezo treat or within 5m after last dose of atezo
-Prior allogeneic stem cell or solid organ transp, Prior treat with CD137agonists or immune checkpoint blockade therapies, including antiCTLA4, antiPD1 and antiPDL1 therapeutic antibodies
-Any other disease, metabolic dysfunction, physical examination finding or clinical lab finding that contraindicates the use of an investing drug, may affect the interpretation of the results or may render the patient at high risk from treat complications
-Known hypers. to CHO cell products or to any component of the atezo or bevacizumab formulation
-Fibrolamellar and sarcomatoid HCC or mixed cholangiocarcinoma and HCC
-Pregnancy/breastfeeding/intention of becoming pregnant during study treat or within at least 5m after last dose atezo, 6m after last dose bevacizumab or 1m after last dose sorafenib
-P. with untreated/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
-Coinfection of hepatitis B/C virus
-Symptomatic, untreated or actively progressing SNC metastases
-Uncontrolled: tumor-related pain, pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
-Uncontrolled/symptomatic hypercalcemia
-Treat with: investing.therapy within 28 d prior study treat, strong CYP3A4 inducers within 14d prior study treat, systemic immunostimulatory agents and immunosuppressive medication within 4w or 5 half-lives of the drug and 2w prior initiation of study treat or anticipation of need for systemic immunosupp. medication during study treat
-Inadequately controlled arterial hypert.
-Sign. vascular disease within 6m prior initiation of study treat
-Metastatic disease that involves major airways or blood vessels or centrally located mediastinal tumor masses of large volume
-Evidence of bleeding diathesis or sign. coagulopathy
-Current/recent use of aspirin or treat with dipyramidole, ticlopidine, clopidogrel, and cilostazol and current/recent use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic p.
-H. of abdo. or tracheoesophageal fistula, GI perforation or intra-abdo. abscess and intra-abdo. inflammatory process within 6m prior study treat, intestinal obstruction and/or clinical signs or symptoms of GI obstruction within 6m prior s
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