Study of Y90-Radioembolization With Nivolumab in Asians With Hepatocellular Carcinoma
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03033446|
Recruitment Status : Recruiting
First Posted : January 26, 2017
Last Update Posted : May 3, 2019
|Condition or disease||Intervention/treatment||Phase|
|HepatoCellular Carcinoma||Radiation: Y-90 Radioembolization Drug: Nivolumab||Phase 2|
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.
To evaluate the response rates of Y90 radioembolization in combination with nivolumab in HCC
- To evaluate time to response, response duration, time to treatment progression and sites of progression when RE is combined with nivolumab
- To assess progression free survival and overall survival when RE is combined with nivolumab
- To assess the quality of life using the FACT-HEP score and EORTC QLQ-C30
- To assess the safety and tolerability of the combination of RE and nivolumab
- To evaluate the relationship between tumor biopsy PD-L1 expression and response to treatment with Y90 radioembolization in combination with nivolumab
- 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.
- 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
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Open-Label, Single Centre, Non-Randomised Trial Of Y90-Radioembolization In Combination With Nivolumab In Asian Patients With Advanced Hepatocellular Carcinoma|
|Study Start Date :||December 2016|
|Estimated Primary Completion Date :||December 2019|
|Estimated Study Completion Date :||December 2019|
|Experimental: Y90-Radioembolization and Nivolumab||
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
Other Name: Selective Internal Radiation Therapy
21 days after Radioembolization, 240mg of IV Nivolumab over 30 minutes will be administered every 2 weeks
Other Name: Opdivo
- Response Rate [ Time Frame: Tumour assessment at 8 weeks ]
- Time to Response [ Time Frame: From date of first dose with Y90 Radioemolization (RE) until best overall response of Complete Response (CR) or Partial Response (PR) is achieved, up to 12 weeks after last dose of Nivolumab ]
- Duration of Response [ Time Frame: From date of first assessment of CR or PR until the first date that progressive disease or death is documented, up to 2 years ]
- Time to Progression [ Time Frame: From date of first dose with Y90 RE until the first date that progressive disease is documented, up to 12 weeks after last dose of Nivolumab ]
- Progression Free Survival [ Time Frame: From date of first dose with Y90 RE until tumour progression, or death from any cause, up to 12 weeks after last dose of Nivolumab ]
- Overall Survival [ Time Frame: From date of first dose with Y90 RE until death from any cause, up to 2 years ]
- Quality of Life using the FACT-HEP score [ Time Frame: From date of screening until 3 months after last dose of Nivolumab ]
- Quality of Life using EORTC QLQ-C30 [ Time Frame: From date of screening until 3 months after last dose of Nivolumab ]
- Adverse events from the combination of RE and nivolumab assessed by NCI CTCAE v4.0 [ Time Frame: While receiving study agent and up to 100 days after last dose of Nivolumab ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03033446
|Contact: Su Pin Choo||+65 6436 firstname.lastname@example.org|
|Contact: Hui Shan Chongemail@example.com|
|National Cancer Centre - Singapore||Recruiting|
|Singapore, Singapore, 169610|
|Contact: Choo Su Pin, MD 65-6436-8000|
|Principal Investigator:||Su Pin Choo, MD||National Cancer Centre, Singapore|