Histotripsy Plus Chemotherapy vs Chemotherapy Alone for Advanced Colorectal Liver Metastasis

Histotripsy Plus Chemotherapy for Advanced Colorectal Liver Metastasis: A Prospective, Single-Armed Trial

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.

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.

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