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

NCT07361107 | Recruiting Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: 25-0632
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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

Conditions

Colorectal (Colon or Rectal) Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Assess the Kinetics of Peripheral Immune Cell Response via T-cells

  2 years

Study Arms (1)

Single Arm

EXPERIMENTAL

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

Interventions

Histotripsy PROCEDURE

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

Single Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Absolute neutrophil count: ≥ 1,000/mcL
• Platelets: ≥ 100,000/mcL
• Total bilirubin ≤ 3x the upper limit of normal (ULN). This may be up to 5x ULN if Gilbert's syndrome is documented.
• AST and ALT ≤ 8x institutional ULN.
• 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.

You may not qualify if:

• 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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• 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.

Sponsors & Collaborators

• Northwell Health: lead

Study Sites (1)

Zuckerberg Cancer Center

New Hyde Park, New York, 11040, United States

RECRUITING

MeSH Terms

Conditions

Colonic Neoplasms

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2025
• First Posted: January 22, 2026
• Study Start: September 26, 2025
• Primary Completion (Estimated): September 27, 2027
• Study Completion (Estimated): September 27, 2027
• Last Updated: January 22, 2026

Record last verified: 2026-01

Locations

US (1)