Histotripsy Plus Chemotherapy vs Chemotherapy Alone for Advanced Colorectal Liver Metastasis

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.

• HistoSonics Edison® System (Device): Histotripsy is a novel, totally non-invasive, non-ionizing, and non-thermal ablation technique that mechanically disrupts tumors through precisely controlled acoustic cavitation. Histotripsy is administered via HistoSonics Edison® System.
• Chemotherapy (Drug): Chemotherapy (standard of care with first line therapy of base of 5-FU with either oxaliplatin or irinotecan).

Primary outcomes

• Radiologic tumor viability [90 days post-treatment]: As assessed by the degree of short-term local tumor control in Colorectal Liver Metastasis(CRLM)

Secondary outcomes

• 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 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 B-cells [30 days post- treatment]: Biopsy results will be used to assess the infiltration of B-cells.
• 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-1 [30 days post-treatment]: Biopsy results will be used to assess the infiltration of PD-1.
• 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.
• Overall Survival [Up to 24 months post-treatment]: Median overall survival will be measured up to 2 years post treatment.
• 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.

Sex: All, ages: 18 Years to any

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 3 months of beginning chemotherapy, or participants who have completed chemotherapy treatment within 1 month of the histotripsy evaluation
* Participants who have undergone other liver-directed therapy, such as ablation, embolization
* Participants with multiple 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 MSI-High
* Participants aged < 18 years
* Pregnant participants

• Federico Aucejo, MD, Principal investigator, Cleveland Clinic, Digestive Disease Institute