The goal of this clinical trial is to learn if using a liver-directed therapy with high dose chemotherapy followed by approved cancer treatment to treat patients with colorectal cancer that has spread to the liver is safe and tolerable. The clinical trial will also learn if the liver-directed therapy with high dose chemotherapy works on the disease in the liver. Investigators will compare the use of the liver-directed therapy with high dose chemotherapy followed by approved cancer treatment or approved cancer treatment alone.
Participants will:
* Undergo up to two liver-directed therapy with high dose chemotherapy procedures followed by approved cancer treatment or take approved cancer treatment alone * Visit clinic at least every two weeks for checkups and tests * Complete scans approximately every two months
Histologically confirmed diagnosis of metastatic colorectal cancer and histologically or cytologically proven CRC metastases that occupy 50% or less of the liver parenchyma.
Patient has liver-dominant metastatic disease. Liver-dominant is defined as the majority of total tumor burden is located in the liver, and the liver lesions are not resectable or treatable with ablation or are associated with extrahepatic disease that makes surgical intervention non-curative.
Disease in the liver must be measurable (per RECIST v.1.1 guidelines) by computed tomography (CT) and/or magnetic resonance imaging (MRI).
If there is evidence of extrahepatic metastatic disease, it is limited, and the life-threatening component of disease is in the liver. Limited extrahepatic disease is defined in this protocol as follows: up to 5 tumor lesions in the lung with longest diameter not greater than 2 cm and/or up to 5 lymph nodes that measure 2 cm or less per lesion; solitary lesions definitively treated with no sign of progression in the last 6 months.
Child-Pugh Class B or C cirrhosis or evidence of clinically significant portal hypertension by history, endoscopy, or radiologic studies (large abdominal varices, prior history of varices by endoscopy).
New York Heart Association functional classification II, III or IV or active cardiac condition(s), including unstable coronary syndromes (unstable or severe angina, recent myocardial infarction), worsening or new-onset congestive heart failure, significant arrhythmias, or severe valvular disease that create(s) undue risks of undergoing general anesthesia.
History or evidence of clinically significant pulmonary disease that precludes the use of general anesthesia.
History of bleeding disorders, presence of brain metastases, or other intracranial abnormalities found on baseline radiologic imaging that would put them at risk for bleeding with anti-coagulation.
Parallel
Melphalan/HDS Followed by Consolidation Treatment with Trifluridine-tipiracil plus Bevacizumab
DrugTrifluridine-tipiracil plus Bevacizumab Alone
Trifluridine-tipiracil plus Bevacizumab Alone
DrugTrifluridine-tipiracil plus Bevacizumab Alone
hPFS
Hepatic Progression Free Survival
PFS
Progression Free Survival
OS
Overall Survival
ORR
Overall Response Rate complete response \[CR\] + partial response \[PR\]
hORR
Hepatic Overall Response Rate
Safety and Tolerability
Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) Changes from baseline in physical examination findings, vital signs, clinical laboratory parameters, electrocardiogram (ECG) and echocardiogram (ECHO) parameters
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