A Study of Atezolizumab in Combination With Bevacizumab in Spanish Patients With Unresectable or Unsuitable for Locoregional Treatments Hepatocellular Carcinoma Not Previously Treated With Systemic Therapy
- Conditions
- Carcinoma, Hepatocellular
- Interventions
- Registration Number
- NCT04732286
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This is a Phase IIIb, one arm, multicenter, open-label study primarily designed to evaluate the safety of atezolizumab + bevacizumab in participants with unresectable or unsuitable for locoregional treatments for metastatic HCC not previously treated with systemic therapy. As part of its secondary objectives, this study is also designed to evaluate the efficacy of atezolizumab and bevacizumab in these participants.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 100
- Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by histology or radiologically, following the AASLD criteria
- 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 detected by CT scan
- Patients who received prior local therapy such as radiofrequency ablation, percutaneous ethanol or acetic acid injection, cryoablation, high-intensity focused ultrasound, transarterial chemoembolization, transarterial embolization (excluding transarterial radioembolization.) 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 version 1.1
- Active or history of autoimmune disease or immune deficiency
- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
- Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
- Co-infection of HBV and HCV
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Arm A (atezolizumab plus bevacizumab) Atezolizumab Participants will receive Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Arm A (atezolizumab plus bevacizumab) Bevacizumab Participants will receive Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
- Primary Outcome Measures
Name Time Method Number of Participants Who Discontinued Atezolizumab and/or Bevacizumab Due to Adverse Events (AE) of Grade ≥ 3 From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months) AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. The severity of AEs was assessed using National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) with the following grades: Grade 1 = asymptomatic or mild symptoms; Grade 2 = minimal, local, or non-invasive intervention indicated; Grade 3 = severe or medically significant, but not immediately life-threatening; Grade 4 = life-threatening consequences or urgent intervention indicated and Grade 5 = death related to AE.
- Secondary Outcome Measures
Name Time Method Change From Baseline in International Normalized Ratio (INR) Baseline up to Cycle 42 (1 cycle = 21 days) The INR is a standardized measure of the prothrombin time. Blood samples were collected from participants to evaluate coagulation parameters.
Change From Baseline in Albumin-Bilirubin (ALBI) Score Baseline up to Cycle 42 (1 cycle = 21 days) Blood samples were collected from participants to evaluate of ALBI grades. ALBI assessment grades of 1 to 3 was based on ALBI score calculation. ALBI score= log10 bilirubin (micromole per liter) \[μmol/L\] × 0.66 + albumin (grams per liter) \[g/L\] × -0.0852. ALBI score ≤ -2.60 = ALBI grade 1; -2.60 \< ALBI score ≤ -1.39 = ALBI grade 2 and -1.39 \< ALBI score = ALBI grade 3.
Percentage of Participants With Ascites and/or Hepatic Encephalopathy Up to approximately 32 months Deterioration of hepatic function was monitored by presence of ascites and/or hepatic encephalopathy.
Overall Survival (OS) Up to 35 months OS was defined as the time from initiation of study treatment to death from any cause. OS was analyzed using Kaplan-Meier (K-M) methods and Greenwood's formula. Any participant who did not die during the study was censored at the last known date to be alive.
Progression-free Survival (PFS) Up to 35 months PFS was defined as the time from initiation of study treatment to the first occurrence of disease progression (PD) or death from any cause (whichever occurs first), as determined by the investigator according to Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1). PD was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥ 5 millimeters (mm). PFS was analyzed using K-M methods and Greenwood's formula. Any participant who did not experience disease progression or death during the study and were censored at the last known date to be alive or without disease progression.
Objective Response Rate (ORR) Up to 35 months ORR = percentage of participants with a complete or partial response (CR or PR), on 2 consecutive investigator assessments ≥ 4 weeks apart in participants with measurable disease at baseline as determined by the investigator according to RECIST v1.1. CR = disappearance of all target lesions and any pathological lymph nodes must have a reduction in short axis to \< 10 mm. PR = at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. Participants without a post-baseline tumor assessment were considered non-responders. 95% confidence interval (CI) was derived using Wilson score intervals. Percentages have been rounded off.
Time to Progression (TTP) Up to 35 months TTP was defined as the time from initiation of study treatment to the first occurrence of PD, as determined by the investigator according to RECIST v1.1. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). In addition to the relative increase of 20%, SOD must also demonstrate an absolute increase of ≥ 5 mm. TTP was analyzed using K-M methods and Greenwood's formula. Any participant who had no disease progression was censored at the last known date without disease progression.
Duration of Response (DOR) Up to 35 months DOR was defined as the time from the first occurrence of a documented objective response (CR or PR) to PD or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1. CR was defined as disappearance of all target lesions and any pathological lymph nodes must have a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥ 5 mm. DOR was analyzed using K-M methods and Greenwood's formula. Any participant who did not experience disease progression or death during the study was censored at the last known date to be alive or without disease progression.
Percentage of Participants Who Started Second-line Treatment Up to 35 months Participants who started second-line of treatment were assessed. Percentages have been rounded off.
Trial Locations
- Locations (25)
Hospital Universitario Reina Sofia
🇪🇸Cordoba, Spain
Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico
🇪🇸Jaen, Spain
Hospital Lucus Augusti
🇪🇸Lugo, Spain
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Clinica Universidad de Navarra Madrid
🇪🇸Madrid, Spain
Clinica Universitaria de Navarra
🇪🇸Pamplona/iruña, Navarra, Spain
Hospital de Basurto
🇪🇸Bilbao, Vizcaya, Spain
Hospital General Univ. de Alicante
🇪🇸Alicante, Spain
Complejo Hospitalario Torrecardenas
🇪🇸Almeria, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Clinic i Provincial
🇪🇸Barcelona, Spain
Hospital General Universitario de Elche
🇪🇸Elche, Alicante, Spain
Corporacio Sanitaria Parc Tauli
🇪🇸Sabadell, Barcelona, Spain
Hospital Universitario Marques de Valdecilla
🇪🇸Santander, Cantabria, Spain
Hospital Provincial de Castellon
🇪🇸Castellon de La Plana, Castellon, Spain
Hospital Son Llatzer
🇪🇸Palma de Mallorca, Islas Baleares, Spain
Complejo Hospitalario Universitario de Santiago (CHUS)
🇪🇸Santiago de Compostela, LA Coruna, Spain
Hospital de Gran Canaria Dr. Negrin
🇪🇸Las Palmas de Gran Canaria, LAS Palmas, Spain
Hospital Universitario de Torrejon
🇪🇸Torrejón de Ardoz, Madrid, Spain
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Univ. Nuestra Señora de Valme
🇪🇸Sevilla, Spain
Hospital Universitari i Politecnic La Fe
🇪🇸Valencia, Spain
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain