Colorectal (Colon or Rectal) Cancer
Conditions
Brief summary
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
Detailed description
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
Interventions
PROCEDUREHistotripsy
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, 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
Sponsors
Northwell Health
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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. * Radiographic confirmation of hepatic metastases with computed tomography (CT) or magnetic resonance imaging (MRI), with CT preferred. Imaging must be performed within 60 days of the date of consent. * Adequate organ and marrow function as defined below: 1. Absolute neutrophil count: ≥ 1,000/mcL 2. Platelets: ≥ 100,000/mcL 3. Total bilirubin ≤ 3x the upper limit of normal (ULN). This may be up to 5x ULN if Gilbert's syndrome is documented. 4. AST and ALT ≤ 8x institutional ULN. 5. Serum creatinine ≤ 2x ULN unless on dialysis. * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 3. * Estimated life expectancy of at least 90 days as determined by the treating physician. * Demographic group: There are no restrictions based on race or ethnicity. Efforts will be made to ensure a representative patient population reflecting the diversity of individuals affected by CRCLM. * Ability to understand and willingness to sign a written informed consent document.
Exclusion criteria
* Major surgical procedure or significant traumatic injury within 14 days prior to histotripsy. * Therapy with an investigational drug within 14 days prior to histotripsy. * Clinically significant cardiovascular or cerebrovascular disease, including: * Myocardial infarction within 3 months prior to enrollment. * Unstable angina. * Congestive heart failure (New York Heart Association Classification Class \> II). v. 3.0 22July2025 9 * Serious cardiac arrhythmia (controlled atrial fibrillation or definitively treated arrhythmias via ablation are not considered
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Measure of System Immune Modulation via T-cells | 2 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assess the Kinetics of Peripheral Immune Cell Response via T-cells | 2 years | 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. |
Countries
United States
Outcome results
None listed