NCT03033446

Study of Y90-Radioembolization With Nivolumab in Asians With Hepatocellular Carcinoma

A Phase II Open-Label, Single Centre, Non-Randomised Trial Of Y90-Radioembolization In Combination With Nivolumab In Asian Patients With Advanced Hepatocellular Carcinoma

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: National Cancer Centre, Singapore · Academic / Other
• Sex: All
• Age: 21 Years – 99 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to evaluate the effect of liver-localised radioembolization and nivolumab on liver cancer.

Detailed description

The hypothesis is that liver-localized radioembolization will stimulate tumour and/or HBV specific T cell responses that are associated with favourable patient outcomes and that can be boosted using nivolumab anti-PD1 checkpoint blockade immunotherapy. Primary objective To evaluate the response rates of Y90 radioembolization in combination with nivolumab in HCC Secondary objectives 1. To evaluate time to response, response duration, time to treatment progression and sites of progression when RE is combined with nivolumab 2. To assess progression free survival and overall survival when RE is combined with nivolumab 3. To assess the quality of life using the FACT-HEP score and EORTC QLQ-C30 4. To assess the safety and tolerability of the combination of RE and nivolumab Exploratory objectives 1. To evaluate the relationship between tumor biopsy PD-L1 expression and response to treatment with Y90 radioembolization in combination with nivolumab 2. To assess relationship between blood lymphocyte (e.g., T cell) activation and phenotypic profiles with response to treatment with Y90 radioembolization in combination with nivolumab, using mass cytometry and fluorescence flow cytometry. 3. To assess relationship between HCC tumour mutational burden and response to treatment with Y90 radioembolization in combination with nivolumab using whole-exome sequencing of tumour biopsy samples 4. Where possible, to evaluate antigen-specific T cell responses to known HBV, HCC tumour (including candidate mutation-derived tumour neo-antigens) and other unrelated antigens (e.g. CMV, EBV, Influenza) in the blood and to assess kinetic changes in these responses associated with response to treatment with Y90 radioembolization in combination with nivolumab using mass cytometry and fluorescence flow cytometry. Administration of study drug The first dose of nivolumab will be administered 21 days (+/- 3 days) after completion of RE. \[The dose of Yttrium-90 will be determined as per institution norm by the Nuclear Medicine physician, based on factors such as the subject's Body Surface Area (BSA), the size of the tumour within the liver, and any dose modifications required for percent lung shunting between 10 - 20% on the Tc-99MMA scan\]. The dose given will be intravenous 240mg absolute over 30 minutes. Subsequent doses of nivolumab will be administered in the outpatient setting at NCCS. After the first dose, intravenous nivolumab 240mg will be given every 2 weeks. A US or CT guided liver biopsy will be conducted by an interventional radiologist on C1D8 Subjects will be assessed for the following at EVERY visit: physical examination, ECOG status, vital signs, Child-Pugh score and ALBI score CT or MRI scans to assess response to treatment will be done before cycle 4, 8, 12 and then after every 12 weeks thereafter (±7 days). FACT-HEP and EORTC QLQ C30 version 3.0 questionnaire at cycle 4 and 8. Follow-Up Visit will be done 2-3 months after last dose. Survival updates will be obtained by phone every 3-4 months after the follow-up visit and any new anti-cancer treatment given to the subject will be recorded.

Conditions

• HepatoCellular Carcinoma

Interventions

Type	Name	Description
RADIATION	Y-90 Radioembolization	Dose of Yttrium-90 is determined based on BSA, size of liver tumor, and dose modifications required for percent lung shunting between 10-20% on the Tc-99MMA scan
DRUG	Nivolumab	21 days after Radioembolization, 240mg of IV Nivolumab over 30 minutes will be administered every 2 weeks

Timeline

• Start date: 2016-12-20
• Primary completion: 2019-08-31
• Completion: 2025-12-31
• First posted: 2017-01-26
• Last updated: 2025-01-06

Locations

1 site across 1 country: Singapore