Histotripsy Plus Chemotherapy vs Chemotherapy Alone for Advanced Colorectal Liver Metastasis

Not Applicable

Not yet recruiting

• Conditions: Colorectal Cancer; Liver Metastases; Liver Cancer
• Interventions: Device: HistoSonics Edison® System; Drug: Chemotherapy

• Registration Number: NCT07044362
• Lead Sponsor: Case Comprehensive Cancer Center

Brief Summary

The goal of this clinical trial is to learn if histotripsy plus chemotherapy works to treat unresectable, bilobar liver- confined colorectal cancer liver metastasis (CRLM). The main question this clinical trial aims to answer is:

• Does the management of this condition with uninterrupted palliative chemotherapy and histotripsy demonstrate improved progression-free survival?

Participants will:

* Receive chemotherapy treatment per standard procedure.

* Undergo histotripsy treatment according to current standard procedures at Cleveland Clinic.

* Occasionally receive Computerized Tomography (CT) scan with and without contrast, give biopsy of treated and untreated liver lesions, and participate in a blood draw of up to 3 teaspoons at each in-person visit.

* Participate in genetic testing, as a part of the standard of care for the treatment.

Detailed Description

This is a prospective trial testing the benefits of histotripsy plus chemotherapy for participants with colorectal liver metastasis. Histotripsy has been approved by the FDA with De Novo classification for non-invasive destruction of liver tumors. Up to 100 participants with colorectal cancer liver metastasis will be included.

Study Timeline

• Study First Submitted: 2025-06-23
• Study First Submitted QC: 2025-06-23
• Study First Posted: 2025-06-30
• Status Verified: 2025-07
• Study Start: 2025-07-01
• Last Update Submitted: 2025-07-01
• Last Update Posted: 2025-07-02
• Primary Completion: 2026-04-01
• Study Completion: 2028-04-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Participants with liver-confined colorectal cancer liver metastasis (CRLM) or Participants who have low-volume pulmonary disease along with CRLM.
• Participants receiving first line therapy with base of 5-FU with either oxaliplatin or irinotecan, or who are within one month of beginning chemotherapy.
• Participants who have undergone other liver-directed therapy, such as ablation, embolization.
• Participants with bilobar, unresectable metastases that cannot be completely treated with resection and/or ablation.
• Participants aged ≥18 years

Exclusion Criteria

• Participants with resectable disease.
• Participants with non-pulmonary extra-hepatic disease including but not limited to bone or peritoneal metastasis.
• Participants who are not able to tolerate general anesthesia.
• Participants who have Childs C Cirrhosis.
• Other non-skin malignancy within 2 years of study.
• WBC count < 3,000 /uL.
• Absolute Neutrophil Count < 1,500 /uL.
• History of Non-malignant serious concurrent illness that would increase the risk of histotripsy.
• Participants with BRAF V600E mutated tumors.
• Participants with MSI-High.
• Participants aged < 18 years
• Pregnant participants

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Histotripsy + Chemotherapy	Chemotherapy	All enrolled participants will undergo combined treatment with Histotripsy and chemotherapy without interruption in the chemotherapy.
Histotripsy + Chemotherapy	HistoSonics Edison® System	All enrolled participants will undergo combined treatment with Histotripsy and chemotherapy without interruption in the chemotherapy.

Primary Outcome Measures

Name	Time	Method
Radiologic tumor viability	90 days post-treatment	As assessed by the degree of short-term local tumor control in Colorectal Liver Metastasis(CRLM)

Secondary Outcome Measures

Name	Time	Method
Rate of Tumor Necrosis	30 days post-treatment	Biopsy results will be used to assess the degree of tumor necrosis in treated lesions.
Percentage of Viable Tumor in Lesion	30 days post-treatment	Biopsy results will be used to assess the percentage of lesions that have viable tumor.
Infiltration of B-cells	30 days post- treatment	Biopsy results will be used to assess the infiltration of B-cells.
Infiltration of CD4	30 days post-treatment	Biopsy results will be used to assess the infiltration of CD4.
Infiltration of CD8	Baseline, 30 days post-treatment	Biopsy results will be used to assess the infiltration of CD8.
Infiltration of PD-1	30 days post-treatment	Biopsy results will be used to assess the infiltration of PD-1.
Overall Survival	Up to 24 months post-treatment	Median overall survival will be measured up to 2 years post treatment.
Infiltration of CD45	30 days post-treatment	Biopsy results will be used to assess the infiltration of CD45.
Infiltration of CD68	30 days post-treatment	Biopsy results will be used to assess the infiltration of CD68.
Infiltration of PD-L1	30 days after treatment	Biopsy results will be used to assess the infiltration of PD-L1.
Infiltration of CTLA-4	30 days post-treatment	Biopsy results will be used to assess the infiltration of CTLA-4.
Progression Free Survival (PFS)	Up to 24 months post-treatment	The rate of progression free survival will be measured up to 2 years post treatment.
30 day Complications	30 days post-treatment	The safety profile of the treatment, as measured by the complications at 30 days.
90 day Complications	90 days post-treatment	The safety profile of the treatment, as measured by the complications at 90 days.

Trial Locations

Locations (1)

Cleveland Clinic, Case Comprehensive Cancer Center; 🇺🇸 Cleveland, Ohio, United States