Health Condition 1: C220- Liver cell carcinoma
Conditions
Interventions
Intervention1: Inj Atezolizumab plus Inj bevacizumab: Patients will receive the following treatment regimen in the study
Arm A experimental arm-atezolizumab + bevacizumab
Atezolizumab 1200 mg IV infus
Sponsors
Frankfurter Institut für Klinische Krebsforschung IKF GmbH
Eligibility
Inclusion criteria
Inclusion criteria: Patients must meet all of the following criteria to be eligible for the study 1. Signed Informed Consent Form available 2. Patients more than or equal to 18 years of age at time of signing Informed Consent Form 3. Confirmed hepatocellular carcinoma diagnosis based on histopathological findings from tumor tissue or typical diagnostic imaging on dynamic CT or MRI according to AASLD criteria. 4. Intermediate stage HCC as defined by the following criteria Disease not amenable to curative surgery, liver transplantation or curative ablation BUT disease amenable to TACE at enrollment as judged by the investigator. No massive multinodular pattern preventing adequate TACE No tumor of a diffuse infiltrative HCC type (hypovascular infiltrative tumors with ill-defined borders) Patent portal vein flow No main portal vein invasion/thrombosis on baseline or eligibility imaging. Patients with minimal invasion, (Vp1 and Vp2) may be eligible if no exclusion criteria are violated. No extrahepatic disease Note - Patients with HCC beyond Milan criteria who enter a downstaging protocol may be recruited into the trial if they do not present any exclusion criteria. 5. Patients with recurrence after resection or ablation or after previous TACE (are eligible, if they according to the investigator have an indication for (additional) TACE 6. Child-Pugh score class A or B7 without ascites requiring more than 100 mg of spironolactone or day at enrollment. 7. Eastern Cooperative Oncology Group ECOG performance status of 0 to 1 at enrollment. 8. Adequate organ and bone marrow function 9. Life expectancy of more than or equal to 3 months 10. The following laboratory values obtained less than or equal to 7 days prior to randomization. Total bilirubin less than or equal to 3.0 x the upper limit of normal ULN Urine dipstick for proteinuria less than 2plus within 7 days prior to randomization Patients discovered to have more than or equal to 2plus proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate less than1 g of protein in 24 hours The following other laboratory values measured within 7 days prior to randomization are either normal or if abnormal do not represent a medical contraindication for TACE and atezolizumab or bevacizumab as judged by the investigator: Platelet count, hemoglobin, alanine aminotransferase ALT, aspartate aminotransferase AST, serum creatinine, INR or aPTT, alkaline phosphatase, neutrophil count ANC, and serum albumin. 11. Negative serum pregnancy test done lesser than or equal to 7 days prior to randomization, for females of childbearing potential only. 12. No presence of untreated or incompletely treated varices with bleeding or high-risk for bleeding: Availability of esophagogastroduodenoscopy not older than 6 months in which all size of varices small to large had been assessed and varices were treated per local standard of care prior to randomization. 13. Absence of other severe comorbidities 14. Resolution of any acute, clinically significant treatment-related adverse events from prior therapy or procedure to Grade less than or equal to 1 prior to randomization, with the exception of alopecia. 15. For patients with active hepatitis B virus HBV HBV DNA less than or equal to 2000 IU or mL obtained within 28 days prio
Exclusion criteria
Exclusion criteria: 1.Fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC 2.Prior treatment with atezolizumab or bevacizumab 3.Previous immunotherapy including PD1, PDL1, or CTLA4 inhibitors for HCC 4.Clinically significant ascites requiring nonpharmacologic intervention 5.Recent major surgery or significant trauma within 28 days 6.Significant cardiovascular disease or recent cardiac events 7.Uncontrolled hypertension with systolic greater than or equal to 150 mmHg or diastolic greater than or equal to 100 mmHg 8.Recent use of full dose anticoagulants or thrombolytic agents 9.Arterial or venous thrombotic or embolic events within 6 months 10.Excluded if past biliary procedures or central biliary obstruction 11.Ongoing infection greater than grade 2 as per NCICCTAE version 5.0 12.Seizure disorder requiring medication 13.Prior allogeneic bone marrow or solid organ transplantation 14.Bleeding diathesis or hemorrhage greater than CTCAE grade 3 within 4 weeks 15.Non-healing wounds, ulcers, or bone fractures 16.Renal failure requiring dialysis 17.Hypersensitivity to study drugs or their components 18.HIV or AIDS unless stable on therapy with a CD4 count greater than 200 cells per microliter and undetectable viral load 19.Active tuberculosis 20.Interstitial lung disease or ongoing signs or symptoms 21.History of pulmonary fibrosis, pneumonitis, or active pneumonitis 22.Persistent proteinuria greater than 3.5 grams per 24 hours 23.Pregnant or nursing women 24.Severe concurrent disease or systemic illness 25.Active or history of autoimmune disease with some exceptions 26.Recent systemic immunosuppressive treatment with some exceptions 27.Use of herbal remedies affecting liver or major organ function 28.Recent live attenuated vaccine within four weeks 29.History of malignancy other than HCC within 3 years with some exceptions 30.Recent investigational drug use within 28 days 31.History of non-compliance, substance abuse, or conditions affecting participation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The main purpose of this phase IIIb study is to test the efficacy and safety of atezolizumab in combination with bevacizumab compared to TACE in patients with intermediate stage liver cancer. Primary endpoint is to evaluate Time to failure of treatment strategy (TTFS [assessed every 8 weeks (±7days)]) defined as the time from randomization until death or need for a further therapeutic option.Timepoint: assessed every 8 weeks (±7days) | — |
Secondary
| Measure | Time frame |
|---|---|
| To further characterize the responses obtained with the respective therapeutic strategy and to assess the impact of each therapeutic strategy on liver function over time. Safety objectives To evaluate the safety and tolerability of each therapeutic strategy and their respective impact on Quality of Life. Biomarker objectives To identify prognostic and predictive angiogenic and immune related biomarkers (tissue and circulating) for study endpoints. To evaluate Overall survival,Overall Survival Rate at 24 months, Objective Response Rate, Time to Progression, Time to loss of systemic treatment options,Progression free survival, Duration of Response, Time to deterioration of liver function, Safety and Quality of Life (QoL) endpoints, to analyse target gene expression and immune cell composition by molecular quantitation of select markers and correlated with clinical efficacy.Timepoint: Overall Survival Rate at 24 months | — |
Countries
Germany, India, Spain
Contacts
Public ContactDr Vikas Ostwal
Tata Memorial Centre
Outcome results
None listed