Ignite Creation Date:
2024-10-26 @ 3:40 PM
Last Modification Date:
2024-10-26 @ 3:40 PM
Study NCT ID:
NCT06605664
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-09-18
Brief Title:
Hyperpolarized 13C-MRI in Patients with Hepatocellular Carcinoma Undergoing Radiotherapy Atezolizumab and Bevacizumab
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Hyperpolarized 13C-MRI Metabolomics and Radiomics for Immune Response Prediction in Patients with Hepatocellular Carcinoma Undergoing Radiotherapy Atezolizumab and Bevacizumab
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Increased pyruvate-to-lactate conversion is a hallmark of HCC metabolism In parallel activation of pro-inflammatory immune cells triggers a metabolic switch towards anaerobic glycolysis Hyperpolarized carbon-13 13C pyruvate MRI is a state-of-the-art non-invasive imaging method that offers real-time insights into tissue metabolism Recent studies have demonstrated its promising potential in predicting responses to radiotherapy and immunotherapy in solid tumors given the significance of pyruvate as a downstream metabolite in glycolysis However its application in assessing treatment response in hepatocellular carcinoma HCC patients remains unclear The establishment of quantitative imaging biomarkers for predicting responses to radio-immunotherapy is an unmet need in the management of HCC patients
While radiotherapy RT effectively controls localized tumors through the induction of unrepairable DNA double-stranded breaks DSBs and cell death its therapeutic efficacy on distal non-irradiated tumor cells is limited with out-of-field recurrence being a common pattern of failure in HCC patients treated with high-dose irradiation Atezolizumab anti-programmed death-ligand 1 anti-PD-L1 in conjunction with bevacizumab anti-vascular endothelial growth factor anti-VEGF has recently emerged as the standard first-line systemic treatment for unresectable hepatocellular carcinoma HCC Despite an objective response rate ORR of only 27 the majority of patients succumb to HCC progression and liver failure Our preclinical study Hsieh et al Science Immunology 2022 uncovered that RT when combined with PD-L1PD-1 blockade induces immunogenic cell death and tumor antigen cross-presentation in antigen-presenting cells enhancing systemic antitumor T cell responses in murine tumor models Recent retrospective cohorts suggest that RT targeting all hepatic tumors combined with PD-L1programmed death-1 PD-1 blockade is associated with an improved ORR and median progression-free survival PFS in patients with unresectable HCC demonstrating a favorable safety profile The synergistic antitumor effects of this combination therapy with RT atezolizumab and bevacizumab have led to its increasing adoption in routine clinical practice
This phase II non-randomized trial aims to prospectively investigate the predictive value of hyperpolarized 13C-MRI along with comprehensive metabolomics and radiomics analyses for immune response assessment including tumor control outcomes and toxicity in patients with HCC undergoing radiotherapy atezolizumab and bevacizumab
While radiotherapy RT effectively controls localized tumors through the induction of unrepairable DNA double-stranded breaks DSBs and cell death its therapeutic efficacy on distal non-irradiated tumor cells is limited with out-of-field recurrence being a common pattern of failure in HCC patients treated with high-dose irradiation Atezolizumab anti-programmed death-ligand 1 anti-PD-L1 in conjunction with bevacizumab anti-vascular endothelial growth factor anti-VEGF has recently emerged as the standard first-line systemic treatment for unresectable hepatocellular carcinoma HCC Despite an objective response rate ORR of only 27 the majority of patients succumb to HCC progression and liver failure Our preclinical study Hsieh et al Science Immunology 2022 uncovered that RT when combined with PD-L1PD-1 blockade induces immunogenic cell death and tumor antigen cross-presentation in antigen-presenting cells enhancing systemic antitumor T cell responses in murine tumor models Recent retrospective cohorts suggest that RT targeting all hepatic tumors combined with PD-L1programmed death-1 PD-1 blockade is associated with an improved ORR and median progression-free survival PFS in patients with unresectable HCC demonstrating a favorable safety profile The synergistic antitumor effects of this combination therapy with RT atezolizumab and bevacizumab have led to its increasing adoption in routine clinical practice
This phase II non-randomized trial aims to prospectively investigate the predictive value of hyperpolarized 13C-MRI along with comprehensive metabolomics and radiomics analyses for immune response assessment including tumor control outcomes and toxicity in patients with HCC undergoing radiotherapy atezolizumab and bevacizumab
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None