Hepatocellular Carcinoma
Conditions
Brief summary
The goal of this clinical trial is to evaluate the added value of 166Holmium SIRT to Atezolizumab-Bevacizumab in patients with non resectable HCC. The primary endpoint is the Best Objective Response Rate at 6 months after 166Holmium SIRT according to mRECIST. Participants will be treated by : * Approved first line systemic therapy: Atezolizumab (1200mg Q3W, IV) with Bevacizumab (15mg/kg Q3W, IV) * In combination with 166Holmium selective internal intra-arterial radiation therapy (Quirem Spheres®, the investigational medical device) after a work-up phase considered as "favorable". Participants will be followed up to 12 months after the first cycle of Atezolizumab and Bevacizumab therapy.
Interventions
DEVICEQuiremSpheres
166Holmium selective internal intra-arterial radiation therapy at C1D15 of the Atezolizumab and Bevacizumab therapy
Sponsors
Gustave Roussy, Cancer Campus, Grand Paris
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Simon's two stage design: In the first stage, 23 evaluable patients will be accrued. If there are 7 or fewer responses (complete or partial response) in these 23 patients, the clinical investigation will be stopped for futility. Otherwise, 10 additional evaluable patients will be accrued for a total of 33.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men and women ≥ 18 years old * Patient should understand, sign, and date the written informed consent form prior to any investigation-specific procedures performed. * Patient should be able to comply with investigational procedure, tissue and blood sample collection and willing to comply with investigation visits and procedures as per clinical investigation plan. * Patients must have pathological confirmation of HCC. * HCC classed Barcelona Clinic Liver Cancer (BCLC) stage C * Patient should be considered as non resectable by Multidisciplinary Team and liver surgeon, and non-eligible for liver transplantation * Patient should be eligible for 1st line Atezolizumab and Bevacizumab combination therapy. Patients previously treated by a local therapy are eligible. * Patient with active intrahepatic HCC. * Patients with or without active viral infection (i.e., HCV, HBV) are eligible. In case of active hepatitis B, the patient should be treated with an anti-HBV therapy during the investigational procedure. * Patients should have measurable disease as defined by mRECIST criteria for response assessment. * ECOG status of 0 or 1 (Appendix 2). * Life expectancy of ≥ 12 weeks at the time of informed consent per Investigator assessment. * Adequate organ function as defined by the following: 1. White blood cells (WBCs) ≥ 2000/mL 2. Platelets ≥ 70 × 103/mL 3. Hemoglobin ≥ 8.0 g/dL 4. Creatinine \< 1.5 × ULN or creatinine clearance ≥ 40mL/min (Cockcroft-Gault formula) 5. ALT and AST ≤ 3 × ULN 6. Lipase and amylase ≤ 1.5 × ULN 7. Total bilirubin ≤ 1.5 × ULN * Child-Pugh A, Without history of encephalopathy or clinically significant ascites * Women of childbearing potential (WOCBP) must have a negative urine or serum β-HCG pregnancy test within 7 days prior registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Sexually active female patients must agree to use two methods of effective contraception\*, one of them being a barrier method, or to abstain from sexual activity during the clinical investigation and for at least 6 months after last drug administration of the investigational procedure or must refrain from heterosexual activity during this same period\*\*. \* Acceptable contraceptive methods include single or combined contraceptive methods that result in a failure rate of \< 1% per year, such as: tubal ligation, male sterilization, hormonal implants, proper use of combined oral or injected hormonal methods (e.g., two barrier methods such as a condom and a cervical cap) may be combined to achieve a failure rate of \< 1% per year. Barrier methods must always be supplemented with the use of a spermicide. \*\* Abstinence is acceptable only if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception. * Sexually active males patients must agree to use condom during the clinical investigation and for at least 7 months after the last drug administration of the investigational procedure. Also, it is recommended the childbearing potential female partner uses a highly effective method of contraception for the same duration. * Patients shall be eligible to undergo pre-treatment and on-treatment tumor biopsies. Patients who either do not consent to a pre-treatment tumor biopsy or do not have accessible lesions will not be eligible. * Patients must be affiliated to a social security system or beneficiary of the same
Exclusion criteria
* Patients with a prior malignancy are excluded, except those with prior malignancies treated more than 2 years previously (at the time of informed consent) with curative intent with no evidence of disease during the interval and who are considered by the Investigator to present a low risk for recurrence, will be eligible. * A known or underlying medical condition that, in the opinion of the Investigator, could make the administration of investigational procedure combination hazardous to the subject or could adversely affect the ability of the subject to comply with or tolerate clinical investigation. * Requirement for daily supplemental oxygen * Previous external radiation therapy to the liver * Uncorrectable abnormal vascular anatomy at pre-assessment angiogram that would result in significant reflux to of hepatic arterial blood to the lung, stomach, pancreas or bowel * Complete main portal vein thrombosis * History or active autoimmune disease with the following exceptions: patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone, patients with controlled Type 1 diabetes mellitus on a stable insulin regimen and patients with mild autoimmune skin disorders (such as eczema or atopic dermatitis involving \<10% of the skin) may be eligible for this clinical investigation * Any of the following within the 6 months prior to clinical investigation entry: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack. * A confirmed history of encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent. * Positive blood screen for human immunodeficiency virus (HIV) with acquired immunodeficiency syndrome (AIDS). Patients with controlled HIV infection under anti-retroviral therapy and normal CD4+ T-cell counts (\>500/mm3) could be considered eligible by the investigator if the patient fulfills the other inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate | at 6 months after intervention | complete or partial response |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Type of treatment related adverse events (AEs) and adverse device effects (ADEs) | from start of treatment to 100 days after the administration of SIRT | regarding to NCI-CTCAE v5.0 |
| Frequency of treatment related adverse events (AEs) and adverse device effects (ADEs) | from start of treatment to 100 days after the administration of SIRT | regarding to NCI-CTCAE v5.0 |
| Severity of treatment related adverse events (AEs) and adverse device effects (ADEs) | from start of treatment to 100 days after the administration of SIRT | regarding to NCI-CTCAE v5.0 |
| Progression Free Survival (PFS) | at 12 weeks, at 6 months and at 12 months | Evolution of Progression Free Survival (PFS) |
| Liver PFS | at 12 weeks, at 6 months and at 12 months | Evolution of liver PFS |
| Overall Survival (OS) | at 12 weeks, at 6 months and at 12 months | Evolution of Overall Survival (OS) |
| Objective Response Rate (ORR) | at 12 weeks, at 6 months and at 12 months | Evolution of Objective Response Rate (ORR) |
| Evaluate alternative response evaluation criteria | from start of treatment to last follow-up visit | iRECIST, itRECIST |
Countries
France
Outcome results
None listed