Advanced liver cancers MedDRA version: 21.0 Level: LLT Classification code 10019828 Term: Hepatocellular carcinoma non-resectable System Organ Class: 100000004864 MedDRA version: 20.0 Level: LLT Classification code 10027479 Term: Metastatic liver carcinoma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: AVASTIN
Product Name: BEVACIZUMAB
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: BEVACIZUMAB
CAS Number: 216974-75-3
Current Sponsor code: RO4876646
Concen
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Stage 1 • Aged >= 18 years • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 within 7 days prior to randomization • Locally advanced or metastatic and/or unresectable hepatocellular carcinoma (HCC) with diagnosis confirmed by histology/cytology or clinically by American Association for the Study of Liver Diseases criteria in cirrhotic patients • Child-Pugh class A within 7 days prior to randomization • Disease that is not amenable to curative surgical and/or locoregional therapies • No prior systemic treatment for HCC • Life expectancy >= 3 months • Availability of a representative tumor specimen that is suitable for determination of PD-L1 and/or additional biomarker status via central testing Stage 1 and Stage 2 • Measurable disease according to Response Evaluation Criteria in Solid Tumors v1.1 • Adequate hematologic and end-organ function within 7 days prior to initiation of study treatment • Documented virology status of hepatitis, as confirmed by screening tests for hepatitis B virus (HBV) and hepatitis C virus (HCV) • Negative HIV test at screening • For women of childbearing potential:agreement to remain abstinent or use contraception and for men:agreement to remain abstinent or use contraception and agreement to refrain from donating sperm Stage 2 • ECOG Performance Status of 0, 1 or 2 • Ability to initiate Stage 2 treatment within 3 months after experiencing unacceptable toxicity not related to atezolizumab or loss of clinical benefit as determined by the investigator while receiving Stage 1 treatment • Availability of a tumor specimen from a biopsy performed upon discontinuation of Stage 1 (if deemed clinically feasible) 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 84 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 16
Exclusion criteria
Exclusion criteria: Stage 1 •Prior treatment with CD137 agonists or immune checkpoint inhibitors •Treatment with investigational therapy within 28 days prior to initiation of study •Treatment with locoregional therapy to liver within 28 days prior to initiation of study or non-recovery from side effects of any such procedure •Untreated or incompletely treated esophageal and/or gastric varices with bleeding or at high risk for bleeding •Prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study •AEs from prior anti-cancer therapy that have not resolved to Grade325 mg/day) or treatment with clopidogrel,dipyramidole,ticlopidine or cilostazol •Current or recent use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylactic) purpose •Core biopsy or other minor surgical procedure within 3 days prior to initiation of study •History of abdominal or tracheoesophageal fistula,GI perforation or intra-abdominal abscess,intestinal obstruction and/or clinical signs/symptoms of GI obstruction •Evidence of abdominal free air not explained by paracentesis or recent surgery •Serious, non-healing/dehiscing wound,active ulcer or untreated bone fracture •Grade >=2 proteinuria •Metastatic disease involving major airways/blood vessels or centrally located mediastinal tumor masses of large volume •History of intra-abdominal inflammatory process •Radiotherapy within 28 days or abdominal/pelvic radiotherapy within 60 days prior to initiation of study with the exception of palliative radiotherapy to bone lesions within 7 days prior to initiation of study •Major surgery, open biopsy or significant traumatic injury within 28 days prior to initiation of study;or abdominal surgery,abdominal interventions or significant abdominal traumatic injury within 60 days prior to initiation of study;or anticipation of need for major surgery during study or non-recovery from side effects of any such procedure •Chronic daily treatment with NSAID •Eligible only for control arm Stage 1 and 2 •Fibrolamellar or sarcomatoid HCC or mixed cholangiocarcinoma and HCC •History of hepatic encephalopathy •Moderate or severe ascites •HBV and HCV coinfection •Symptomatic,untreated or actively progressing CNS metastases •History of leptomeningeal disease •Uncontrolled tumor-related pain •Uncontrolled pleural effusion,pericardial effusion or ascites requiring recurrent drainage procedures •Uncontrolled or symptomatic hypercalcemia •Active or history of autoimmune disease or immune deficiency •History of IPF organizing pneumonia,drug-induced or idiopathic pneumonitis or evidence of active pneumonitis on screening chest CT scan •Active TB •Significant CV disease within 3 months prior to initiation of study,unstable arrhythmia or unstable angina •Major surgery other than for diagnosis within 4 weeks prior to initiation of study or anticipated major surgery during study •History of malignancy other than HCC within 5 years prior to screening •Severe infection within 4 weeks prior to initiation of study •Treatment with therapeutic oral or IV antibiotics within 2 weeks pri
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the efficacy of immunotherapy-based treatment combinations based on objective response rate • To evaluate the safety of immunotherapy-based treatment combinations ;Secondary Objective: • To evaluate the efficacy of immunotherapy-based treatment combinations based on progression-free survival, overall survival after randomization, overall survival at specific timepoints, duration of response, disease control;Primary end point(s): 1. Objective response rate 2. Incidence, nature, and severity of adverse events and laboratory abnormalities 3. Change from baseline in vital signs and ECG parameters 4. Change from baseline in targeted clinical laboratory test results ;Timepoint(s) of evaluation of this end point: 1. From randomization until loss of clinical benefit (up to 5 years) 2-4. From first study treatment administration until 135 days after the last dose or unitl initiation of new systemic anti-cancer therapy, whichever occurs first (up to 5 years) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Progression-free survival 2. Overall survival after randomization 3. Overall survival at specified timepoints 4. Duration of response 5. Disease control ;Timepoint(s) of evaluation of this end point: 1. From randomization to the first occurrence of disease progression (up to 5 years) 2. From randomization to death from any cause (up to 5 years) 3. Approximately every 6 months, up to 5 years 4. From the date of the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to 5 years) 5. From randomization until loss of clinical benefit (up to 5 years) | — |
Countries
Australia, China, France, Israel, Korea, Republic of, New Zealand, Taiwan, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed