This is a single-center, non-randomized, open-label, single-arm pilot study investigating the systemic immune response to histotripsy in patients with colorectal cancer with liver metastasis. Histotripsy is an FDA-approved, non-invasive therapeutic modality for the treatment of liver tumors, including both primary and metastatic lesions. In this study, investigators aim to evaluate the kinetics of peripheral T-cell response following histotripsy of colorectal cancer liver metastases (CRCLM). Given the well-documented immune-tolerant tumor microenvironment of liver metastases and their role in systemic resistance to checkpoint inhibitors, investigators hypothesize that histotripsy-induced tumor disruption will lead to measurable alterations in peripheral T-cell clonal expansion and exhaustion markers. Investigators will assess these changes via serial blood draws before and after histotripsy, with the goal of characterizing the systemic immune impact of local tumor ablation. Findings from this study may inform future combination strategies integrating histotripsy with immunotherapy to enhance treatment response in microsatellite-stable CRC
Gender: Both male and female patients will be eligible for enrollment.
Age at least 18 years.
Histologic (biopsy-proven) confirmation of metastatic microsatellite stable colorectal cancer with at least one radiographically evident hepatic metastasis.
Planned treatment with standard-of-care histotripsy.
Major surgical procedure or significant traumatic injury within 14 days prior to histotripsy.
Therapy with an investigational drug within 14 days prior to histotripsy.
Myocardial infarction within 3 months prior to enrollment.
Unstable angina.
Single group
Histotripsy
Procedure/SurgeryThis is a single-center, non-randomized, open-label, single-arm pilot study investigating the systemic immune response to histotripsy in patients with colorectal cancer with liver metastasis. Histotripsy is an FDA-approved, non-invasive therapeutic modality for the treatment of liver tumors, including both primary and metastatic lesions. In this study, we aim to evaluate the kinetics of peripheral T-cell response following histotripsy of colorectal cancer liver metastases (CRCLM). Given the well-documented immune-tolerant tumor microenvironment of liver metastases and their role in systemic resistance to checkpoint inhibitors, we hypothesize that histotripsy-induced tumor disruption will lead to measurable alterations in peripheral T-cell clonal expansion and exhaustion markers. We will assess these changes via serial blood draws before and after histotripsy, with the goal of characterizing the systemic immune impact of local tumor ablation. Findings from this study may inform future
Measure of System Immune Modulation via T-cells
To evaluate whether histotripsy of CRCLM induces systemic immune modulation, as measured by changes in peripheral T-cell clonal expansion and markers of T-cell exhaustion. Change in peripheral T-cell clonal expansion measured in the week prior to histotripsy, directly after histotripsy, and at 14, 28, and 90 days following histotripsy. Change in markers of T-cell exhaustion measured in the week prior to histotripsy, directly after histotripsy, and at 14, 28, and 90 days following histotripsy.
Assess the Kinetics of Peripheral Immune Cell Response via T-cells
Change in the kinetics of T-cell clonal expansion measured at the week prior to histotripsy, directly after histotripsy, and at 14, 28, and 90 days following histotripsy via blood samples will be analyzed using statistical analysis.
Click on the lead sponsor to view all of their trials.
