Deep, Multi-omics Phenotyping to Predict Response, Resistance and Recurrence to Adjuvant Atezolizumab Plus Bevacizumab in Resected Hepatocellular Carcinoma

Sponsor
National Cancer Centre, Singapore
Study ID
NCT05516628
Phase
PHASE2
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
21 Years - 90 Years
Healthy Volunteers
Not accepted

Interventions

  • Surgical Resection — PROCEDURE
    Resection of Primary Hepatocellular Cancer Tumour.
  • Adjuvant Atezolizumab-Bevacizumab Therapy — DRUG
    Patient receives adjuvant Atezolizumab plus Bevacizumab every 3-weekly for two years following resection of hepatocellular carcinoma tumour.

Study Details

Hepatocellular carcinoma (HCC) is the 7th most common cancer worldwide but is the 4th deadliest, because diagnosis tend to be late and current systemic therapies are poorly efficacious. Within the same tumour, different parts of the HCC can belong to separate molecular sub-groups. In addition, there is currently no validated predictive biomarkers to help clinicians select the best therapy for an individual patient. This challenge poses an urgent, unmet clinical need. To address this, the multi-disciplinary research program Precision Medicine in Liver Cancer across an Asia-Pacific Network (PLANet 1.0) was conceptualized and successfully conducted from 2016-22. The program uncovered novel insights into the highly heterogeneous molecular landscape of HCC and novel mechanisms, including how HCC reverts to fetal forms to escape the body's immunological defence. These investigations will be continued in PLANet 2.0 and in this new phase, the research team will investigate patients receiving best-in-class therapeutics in 2 investigator-initiated clinical studies (AHCC12 and AHCC13), including Atezolizumab plus Bevacizumab (Atezo+Bev) and Yttrium-90, which allows the research team to collect longitudinal, before and after treatment biosamples and clinical data. These clinical studies will serve as proof-of-concept to the study team's translational findings and allow it to uncover predictive biomarkers which will help clinicians to institute more efficacious and personalized treatment in the future. The research team comprises of experts in different complementary fields (epigenomics, genomics, immunomics, metabolomics, proteomics, clinical science and data science) and across different institutions. This allows the team to adopt an integrative approach in understanding the landscape of the HCC tumour micro-environment and biomarkers co-localisation, and their role in tumour evolution and therapeutic response. By adopting a wide spectrum of converging investigations, PLANet 2.0 will identify and validate biomarkers that correlate with clinical outcomes (response, resistance and recurrence).

Key Dates

Start date
Feb 28, 2023
Status verified
Jun 2025
Primary completion
Mar 31, 2027
Completion
Mar 31, 2027

Study Design

Enrollment
30 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Surgery followed by Adjuvant Atezolizumab-Bevacizumab Therapy every 3-weekly
    Patient will receive adjuvant Atezolizumab plus Bevacizumab every 3-weekly for two years following surgery.

Primary Outcome Measure

Recurrence-free-survival (RFS) in relation to the multi-omics (epigenomics, genomics, transcriptomics, proteomics and metabolomics) and spatial TME profiles of both tissue and peripheral blood. [ Time Frame: Up to 4 Years after surgery. ]

Central Contacts

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