Atezolizumab for Hepatocellular carcinoma (unresectable)

Inclusion criteria

• {"criterion_text":"- Signed Informed consent Form."}
• {"criterion_text":"- Age ≥ 18 years."}
• {"criterion_text":"- Tolerance to first line treatment for HCC with Atezolizumab plus Bevacizumab, i.e. absence of adverse events requiring definitive interruption of any of the two drugs."}
• {"criterion_text":"- Ability to comply with the study protocol, in the investigator’s judgment."}
• {"criterion_text":"- Unresectable HCC displaying early disease progression to first-line therapy with Atezolizumab and Bevacizumab (within 4 months from the start of the treatment)."}
• {"criterion_text":"- At least one measurable (per RECIST 1.1) untreated lesion."}
• {"criterion_text":"- ECOG-PS: 0-1, Child-Pugh A."}
• {"criterion_text":"- Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 7 days prior to recruitment [...]:"}
• {"criterion_text":"- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs, as defined below."}
• {"criterion_text":"- Women must remain abstinent or use contraceptive methods with a failure rate of < 1% per year while they are receiving atezolizumab and bevacizumab and for 5 months after the final dose of atezolizumab and for 6 months after the final dose of bevacizumab."}
• {"criterion_text":"- Women must refrain from donating eggs during the same period"}
• {"criterion_text":"- Men with female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of <1% per year during the treatment period and for 6 months after the last dose of bevacizumab."}
• {"criterion_text":"- Men must refrain from donating sperm during this same period."}

Exclusion criteria

• {"criterion_text":"- History of leptomeningeal disease or brain metastases."}
• {"criterion_text":"- Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with some expceptions (see full protocol for details)."}
• {"criterion_text":"- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan."}
• {"criterion_text":"- Active tubercolosis."}
• {"criterion_text":"- Significant cardiovascular disease (...) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina"}
• {"criterion_text":"- History of congenital long QT syndrome or corrected QT interval >500 ms (...) at screening"}
• {"criterion_text":"- Active malignancy in advanced stage other than HCC within 1 year prior to screening (....)"}
• {"criterion_text":"- Prior severe adverse reaction to either Atezolizumab or Bevacizumab which either was not manageable with low dose steroid therapy or required a treatment interruption."}
• {"criterion_text":"- History of uncorrectable electrolyte disorder affecting serum levels of potassium, calcium, or magnesium"}
• {"criterion_text":"- Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study"}
• {"criterion_text":"- Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia or any active infection that could impact patient safety"}
• {"criterion_text":"- Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment"}
• {"criterion_text":"- Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease (COPD) exacerbation) are eligible for the study. Antibiotics administered within 30 days prior to initiation of study treatment have to be recorded in eCRF."}
• {"criterion_text":"- Prior allogeneic stem cell or solid organ transplantation"}
• {"criterion_text":"- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications"}
• {"criterion_text":"- Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the last dose of atezolizumab"}
• {"criterion_text":"- History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins"}
• {"criterion_text":"- Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab or bevacizumab formulation"}
• {"criterion_text":"- Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within at least 5 months after the last dose of atezolizumab and 6 months after the last dose of bevacizumab"}
• {"criterion_text":"- Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment"}
• {"criterion_text":"- Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC"}
• {"criterion_text":"- Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high-risk for bleeding (see full protocol for details)"}

Primary endpoints

• {"endpoint_text":"- for safety: incidence of adverse events of grade > 3","definition_or_measurement_approach":""}
• {"endpoint_text":"- for efficacy: disease control rate (according to RECIST 1.1) at 12 weeks after FMT. Disease control is defined as complete response, partial response and stable disease.","definition_or_measurement_approach":"Disease control rate measured per RECIST 1.1 at 12 weeks after FMT; disease control defined as complete response, partial response or stable disease."}

Secondary endpoints

• {"endpoint_text":"- Characterization of patients’ microbiota both before and after FMT in terms of diversity and abundance of different microbiomal populations","definition_or_measurement_approach":"Microbiota diversity and abundance analyses before and after FMT (methodology not specified in the provided record)."}
• {"endpoint_text":"- Blood biomarkers: characterization of neutrophil and lymphocytic populations in terms of PD-1 PD-L1 expression, Neutrophil and Lymphocytes ratios, markers of inflammation (C-reactive proteins), LDH, RNAseq patterns","definition_or_measurement_approach":"Characterization of blood biomarkers including PD-1/PD-L1 expression, neutrophil:lymphocyte ratio, CRP, LDH and RNAseq patterns (specific assays/timing not specified)."}

Italy

Earliest CTIS Part Ii Submission Date

07-08-2024

Latest Decision Or Authorization Date

19-08-2024

Processing Time Days

12

Number Of Sites

1

Number Of Participants

15

Primary sponsor

Full Name

Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy