Evaluation of Circulating Immune Response After Histosonics in Colorectal Cancer (ECHO-CRC) (ECHO CRC)

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

Study Overview

• Status: Recruiting
• Conditions: Colorectal (Colon or Rectal) Cancer
• Intervention / Treatment: Procedure: Histotripsy

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

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New Hyde Park, New York, United States, 11040
      • Recruiting
      • Zuckerberg Cancer Center
      • Contact: GI Referral Team GI Referral Team; Phone Number: 516-734-8900; Email: gitrialreferral@northwell.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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).

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    • Serious cardiac arrhythmia (controlled atrial fibrillation or definitively treated arrhythmias via ablation are not considered exclusion criteria).
    • Cerebrovascular stroke with deficit within 3 months prior to enrollment.
  • Active infection requiring systemic therapy within 14 days prior to histotripsy, unless deemed to be a chronic disease state by the study PI.
  • Active pregnancy.
  • Patients with active infections, autoimmune diseases requiring systemic immunosuppression, or other uncontrolled comorbidities that could interfere with study participation will be excluded.
  • Severe cancer-associated cachexia that may interfere with systemic immune response, as assessed by the treating physician.

  • Any ongoing medical illness or injury that would significantly impact tolerability of therapy, including but not limited to:

    • Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture.
    • Clinical signs or symptoms of gastrointestinal obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding.
    • Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates histotripsy, may affect the interpretation of study results, or may render the patient at high risk for treatment complications.
  • Anyone that is unable to consent due to cognitive, psychological or other reasons that impact their capacity.
  • Deemed to be inappropriate for enrollment by the study PI.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Single Arm; 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

Procedure: Histotripsy; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	2 years

Collaborators and Investigators

• Sponsor: Northwell Health

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2025
• Primary Completion (Estimated): September 27, 2027
• Study Completion (Estimated): September 27, 2027

Study Registration Dates

• First Submitted: December 10, 2025
• First Submitted That Met QC Criteria: January 14, 2026
• First Posted (Actual): January 22, 2026

Study Record Updates

• Last Update Posted (Actual): January 22, 2026
• Last Update Submitted That Met QC Criteria: January 14, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Colonic Diseases; Colonic Neoplasms
• Other Study ID Numbers: 25-0632

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No