A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients with Advanced Liver Cancers (Morpheus-Liver)
- Conditions
- Advanced liver cancersMedDRA version: 21.0Level: LLTClassification code 10019828Term: Hepatocellular carcinoma non-resectableSystem Organ Class: 100000004864MedDRA version: 20.0Level: LLTClassification code 10027479Term: Metastatic liver carcinomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-001743-10-FR
- 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
- 100
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
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 Grade<= 1 or better with the exception of alopecia of any grade
•Inadequately controlled hypertension
•History of hypertensive crisis or hypertensive encephalopathy
•Significant vascular disease
•History of hemoptysis within 1 month prior to initiation of study
•Evidence of bleeding diathesis or significant coagulopathy
•Current or recent use of asprin (>325 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
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