Clinical Investigation Evaluating Safety and Efficacy of Selective Intra-arterial 166Holmium Radiation Therapy in Combination With Atezolizumab and Bevacizumab for Non Resectable Hepatocellular Carcinoma

NCT05705791 | Active Not Recruiting DMC

• 2 other identifiers: 2022-001749-192021/3330
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 6

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.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  complete or partial response

  at 6 months after intervention

Secondary Outcomes (8)

• Type of treatment related adverse events (AEs) and adverse device effects (ADEs)

  from start of treatment to 100 days after the administration of SIRT

• Frequency of treatment related adverse events (AEs) and adverse device effects (ADEs)

  from start of treatment to 100 days after the administration of SIRT

• Severity of treatment related adverse events (AEs) and adverse device effects (ADEs)

  from start of treatment to 100 days after the administration of SIRT

• Progression Free Survival (PFS)

  at 12 weeks, at 6 months and at 12 months

• Liver PFS

  at 12 weeks, at 6 months and at 12 months

Study Arms (1)

166Holmium SIRT arm

EXPERIMENTAL

166Holmium selective internal intra-arterial radiation therapy (QuiremSpheres®, experimental medical device) in combination with approved first line therapy: * Atezolizumab1200mg Q3W IV * Bevacizumab 15mg/kg Q3W IV

Device: QuiremSpheres

Interventions

QuiremSpheres DEVICE

166Holmium selective internal intra-arterial radiation therapy at C1D15 of the Atezolizumab and Bevacizumab therapy

Also known as: 166Holmium microspheres, 166Holmium SIRT

166Holmium SIRT arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• White blood cells (WBCs) ≥ 2000/mL
• Platelets ≥ 70 × 103/mL

You may not qualify if:

• 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.
• Any other significant acute or chronic medical illness. Any other sound medical, psychiatric, and/or social reason as determined by the Investigator.
• Subjects who are unable to undergo and/or tolerate venous AND arterial access (evaluated on pre-treatment imaging)
• Any other investigational drug
• Any anticancer therapy (chemotherapy, biologics, therapeutic vaccines, radiotherapy, or hormonal treatment).
• Treatment with capecitabine within two months prior to treatment, or patient who will be treated with capecitabine at any time following treatment with QuiremSpheres®
• Concomitant use of herbal therapies/traditional Chinese medicine with anti-cancer activity included in the label is not permitted because of potential drug-drug interactions.

Sponsors & Collaborators

• Gustave Roussy, Cancer Campus, Grand Paris: lead

Study Sites (6)

AP-HP Hôpital Beaujon

Clichy, 92110, France

Location

Centre Georges-François Leclerc

Dijon, 21000, France

Location

CHU François Mitterand

Dijon, 21000, France

Location

Hôpital Saint Eloi

Montpellier, 34000, France

Location

CHU Nantes

Nantes, 44000, France

Location

Gustave Roussy

Villejuif, 94800, France

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: January 17, 2023
• First Posted: January 31, 2023
• Study Start: February 7, 2023
• Primary Completion: February 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: July 5, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (6)