Durvalumab with Gemcitabine and Cisplatin for the Treatment of High-Risk Resectable Liver Cancer Before Surgery

Summary

Objectives

PRIMARY OBJECTIVE:
I. To examine the proportion of patients who complete neoadjuvant therapy followed by curative intent surgical resection.

SECONDARY OBJECTIVES:
I. To determine the major pathologic response (MPR) rate. (Efficacy)
II. To determine the proportion of patients who attain an R0 resection following neoadjuvant therapy. (Efficacy)
III. To determine the radiological response rate after 2 and 4 cycles of neoadjuvant therapy. (Efficacy)
IV. To determine the overall survival of patients receiving neoadjuvant therapy prior to curative intent surgical resection. (Efficacy)
V. To determine the relapse free survival (RFS) of patients receiving neoadjuvant therapy prior to curative intent surgical resection. (Efficacy)
VI. To estimate the incidence of adverse events during neoadjuvant therapy which would preclude completion of the neoadjuvant chemotherapy regiment as defined by grade 4 or above adverse events by Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. (Feasibility)
VII. To determine the proportion of patients who are able to start adjuvant therapy within 10 weeks of surgical resection. (Feasibility)
VIII. To determine the proportion of patients who can complete 4 cycles of adjuvant therapy. (Feasibility)
IX. To determine the efficacy of therapy in different molecular subtypes (by deoxyribonucleic acid [DNA] profiling, ribonucleic acid [RNA] profiling, and circulating tumor [ct]DNA-based minimal residual disease [MRD]). (Toxicity Profiles and Biomarkers)
X. To compare pre- and post-neoadjuvant therapy changes in the phenotypic profiles of circulating immune cells. (Toxicity Profiles and Biomarkers)
XI. To correlate ctDNA-based MRD, tissue and blood based immune biomarkers, and body composition with the primary/secondary endpoints. (Toxicity Profiles and Biomarkers)

EXPLORATORY OBJECTIVES:
I. Quantitative European Association for the Study of the Liver (qEASL)-based 3 dimensional (3D) enhancement measurement will be used as a surrogate marker of pathological response.
II. The primary and secondary outcomes will be associated with the visceral abdominal fat, subcutaneous abdominal fat, and muscle at the level of L2/L3.

OUTLINE:
Patients receive durvalumab intravenously (IV) over 60 minutes on day 1 with gemcitabine IV over 30 minutes and cisplatin IV over 60 minutes on days 1 and 8 for 4 cycles and then undergo surgical resection on study. Following surgery, patients may continue the durvalumab, gemcitabine and cisplatin regimen for up to 4 additional cycles. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo computed tomography (CT) scans and/or magnetic resonance imaging (MRI) scans and blood sample collection throughout study, as well as tissue biopsies during screening and on study.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 5 years and then yearly.