GSL Synthetase Inhibitor Plus Immune Checkpoint Inhibitor and/or Regorafenib in Previously Treated pMMR/MSS CRC.
NCT Number: NCT06558773
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Colorectal Cancer
Interventions: DRUG: Eliglustat+Immune checkpoint inhibitor+Regorafenib|DRUG: Eliglustat+Immune checkpoint inhibitor|DRUG: Regorafenib+Immune checkpoint inhibitor
Sponsor: Chinese PLA General Hospital
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 120
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-09-01
Completion Date: 2027-08-31
Locations: China, Beijing, Biotherapeutic Department Of Chinsese PLA Gereral Hospital, China

Summary:
In this single-center,open-label, randomized, phase II study, the efficacy and feasibility of GSL synthetase inhibitor in combination with immune checkpoint inhibitor and/or regorafenib therapeutic regimen will be evaluated in patients with advanced/metastatic proficient mismatch repair/microsatellite stable (pMMR/MSS) colorectal cancer (CRC).In this clinical trial, a total of 120 eligible patients were stratified randomly (with/without liver metastases) assigned to the 3 arms in a 1:1:1 ratio: experimental group-arm A(Eliglustat+Immune checkpoint inhibitor+Regorafenib),experimental group-arm B(Eliglustat+Immune checkpoint inhibitor) and comparator group-arm C(Regorafenib+Immune checkpoint inhibitor).It aims to: 1).assess the antitumor effects of GSL synthetase inhibitor in combination with immune checkpoint inhibitor and/or regorafenib;2).evaluate the immunological or clinical predictive biomarkers for efficacy and toxicity; 3).detect the transformation of tumor microenvironment (TME) and dynamic changes of immune cells in peripheral blood after the treatment with GSL synthetase inhibitor in combination with immune checkpoint inhibitor and/or regorafenib.

Primary Outcome Measures: Objective response rate (ORR), Objective response rate includes complete response and partial response defined by investigators according to RECIST 1.1or iRECIST criteria., Up to 120 days after the last dose of study drugs
Secondary Outcome Measures: Progression Free Survival (PFS), Time from the date of first administration of the study drug to disease progression or death from any cause (any earliest date)., Up to 2 years|Overall Survival (OS), Time from the date of first administration of the study drug to the date of death., Up to 2 years
Other Outcome Measures: Immunological response (cytokines, lymphocyte phenotype), The concentration of cytokines (mainly include interleukin-2(IL-2), interleukin-6(IL-6),tumor necrosis factor α (TNF-α), the unit is picograms per milliliter) in tumor beds and peripheral blood and the changes of lymphocyte phenotype ( mainly include the number and percentage of cluster of differentiation 4(CD4+) and CD8+ T cells) following the treatment, will be assessed by quantitative polymerase chain reaction (qPCR) and flow cytometer., Up to 120 days after the last dose of study drugs]|Biomarkers predictive of response and toxicity, Biomarkers from tumor cells, lymphocytes and tumor microenvironment will be assessed for their potential in predicting clinical response and toxicity.All participants with treatment-related adverse events (AE) as assessed by National Cancer Institute Common Terminology Criteria for Adverse Event, Version 5.0(CTC AE 5.0)., Up to 120 days after the last dose of study drugs]