Four major medical institutions are collaborating to carry out a multi–modality clinical trial which may lead to the development of a new treatment strategy for liver cancer.

The investigator–initiated Phase 2 trial will be studying the combination of two treatments, Yittrium–90 (Y90) SIR–Spheres microspheres radioembolisation and Nivolumab.

Y90 radioembolisation is currently used for liver cancer patients who are unsuitable for surgery or liver transplantation. Nivolumab, an immunotherapy drug that enhances the body’s immune response against cancer cells, is showing very promising results for advanced liver cancer patients in ongoing studies. Nivolumab has also been shown to enhance the effects of radiation in various cancers. Furthermore, immunotherapy drugs like nivolumab when combined with radiation have been observed to cause an abscopal effect, where localised treatment of a tumour not only shrinks the treated tumour, but also tumours in other parts of the body that are not irradiated.

Thus, the aim of this trial is to show that nivolumab can enhance the effects of radioembolisation in liver cancer and further improve outcomes for patients.

This approach is the first in the world and is supported by Singapore Ministry of Health’s National Medical Research Council under its Clinician Scientist–Individual Research Grant (NMRCCIRG/1454/2016), Bristol–Myers Squibb and Sirtex.

“Nivolumab has shown some initial promising activity in advanced liver cancer and studies are ongoing. Therefore there is a rationale to conduct this study in earlier stages of liver cancer. Y90 radioembolisation is often used to treat liver cancer. SGH and NCCS have extensive experience with this modality of treatment. We plan to study whether nivolumab may help to further enhance the efficacy of radioembolisation. If proven so, this will change the way we treat liver cancers.” said Dr Choo Su Pin, a Senior Consultant Medical Oncologist with National Cancer Centre Singapore (NCCS), and Adjunct Associate Professor, Oncology Academic Clinical Programme with Duke–NUS Medical School. She is also the Lead Principal Investigator of this study.

Besides Dr Choo, the other Co–Investigators involved include Dr David Tai, Consultant Medical Oncologist, NCCS, who is also an Adjunct Associate Professor, Oncology Academic Clinical Programme with Duke–NUS Medical School, Adjunct Associate Professor David Ng, Head and Senior Consultant, Department of Nuclear Medicine & PET, Singapore General Hospital (SGH), Dr Apoorva Gogna, Consultant, Department of Diagnostic Radiology, SGH, Dr Zhai Weiwei, Senior Research Scientist, Human Genetics, Genome Institute of Singapore, and Adjunct Assistant Professor Evan Newell, Principal Investigator, Singapore Immunology Network.

The trial, which started since December 2016, is planned to be completed in two years. Patients who have un–resectable liver cancer and are eligible for radioembolisation will be offered participation in the study. 40 patients will be recruited at the NCCS. Patients will first be administered the Y90 radioembolisation at SGH. Nivolumab will be given through an intravenous (IV) infusion 21 days later, and every 2 weeks thereafter.

Besides evaluating the response rates of the combined treatments, the team aims to assess its progression–free survival and overall survival, quality of life and safety and tolerability.