RECRUITING

Evaluation of the Safety and Efficacy of Treatment w/High Dose Melphalan Given Directly Into the Liver Followed by Treatment w/Approved Cancer Treatment or Approved Cancer Treatment Alone in Patients w/ Metastatic Colorectal Cancer w/Liver Dominant Disease

Conditions

Refractory Metastatic Colorectal Cancer melphalan/HDS melphalan/hepatic delivery system trifluridine-tipiracil trifluridine-tipiracil (FTD-TPI)trifluridine-tipiracil (FTD-TPI) plus bevacizumab trifluridine-tipiracil plus bevacizumab hepatic delivery system melphalan liver dominant disease colorectal cancer metastatic colorectal cancer rectal cancer

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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

Official Title

An Open-label, Randomized, Multi-Center Study to Evaluate the Efficacy and Safety of Induction Treatment With Melphalan/HDS Followed by Consolidation Treatment With Trifluridine-Tipiracil Plus Bevacizumab Versus Trifluridine-Tipiracil Plus Bevacizumab Alone in Patients With Refractory Metastatic Colorectal Cancer With Liver Dominant Disease

Quick Facts

Study Start:2025-08-05

Study Completion:2027-10

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06607458

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 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. * Scans used to determine eligibility (CT scan of the chest/abdomen/pelvis and MRI of the liver) must be performed within 28 days prior to randomization. * Previous treatment and progressed on or following, or intolerant to, fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and/or an anti-EGFR therapy if RAS wild-type. * ECOG PS of 0-1 within 14 days prior to randomization.	* 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. * Known varices at risk of bleeding, including medium or large esophageal or gastric varices, active peptic ulcer, or history of recent hemoptysis. * Active second malignancy, or has history of recently definitively treated invasive cancer in the past 2 years prior to enrolment with the exception of non-melanoma skin cancer. * Peritoneal lesions or large abdominal masses. * Use of immunosuppressive drugs. * Inability to temporarily stop chronic anti-coagulation therapy. * Active bacterial infections with systemic manifestations. * Active viral infection, including Hepatitis B and Hepatitis C infection. NOTE: Patients with anti-hepatitis B core antibody (HBc) positive, or hepatitis B surface antigen (HBsAg) but DNA negative are allowed exception(s). * Severe allergic reaction to iodine contrast that cannot be controlled by premedication with antihistamines and steroids. * History of or known hypersensitivity to melphalan or the components of the melphalan/HDS system. * History of known hypersensitivity to heparin or the presence of heparin-induced thrombocytopenia. * Uncontrolled endocrine disorder including diabetes mellitus, hypothyroidism, or hyperthyroidism. * Received anti-cancer therapy including radiotherapy or investigational agent for any indication ≤ 30 days prior to randomization * Previous treatment with trifluridine-tipiracil. * History of allergic reactions attributed to compounds of similar composition to trifluridine/tipiracil or any of its excipients. * Hereditary problems of galactose intolerance, total lactase deficiency or glucosegalactose malabsorption. * History of allergic reactions or hypersensitivity to bevacizumab or any of its excipients. * History of hypersensitivity to Chinese Hamster Ovary cell products or other recombinant human or humanized antibodies. * Contraindications to bevacizumab, including uncontrolled hypertension, history of active fistula or bowel perforation (unless in the setting of a resected primary), history of CVA or arterial thrombotic event in the last 1 year, or history of venous thrombotic event in the last 30 days. * Evidence of hepatic vein or portal vein thrombosis * Prior chemoembolization or radioembolization to the liver or prior hepatic arterial infusion therapy

Inclusion Criteria

Exclusion Criteria

* 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.
* Scans used to determine eligibility (CT scan of the chest/abdomen/pelvis and MRI of the liver) must be performed within 28 days prior to randomization.
* Previous treatment and progressed on or following, or intolerant to, fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and/or an anti-EGFR therapy if RAS wild-type.
* ECOG PS of 0-1 within 14 days prior to randomization.

* 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.
* Known varices at risk of bleeding, including medium or large esophageal or gastric varices, active peptic ulcer, or history of recent hemoptysis.
* Active second malignancy, or has history of recently definitively treated invasive cancer in the past 2 years prior to enrolment with the exception of non-melanoma skin cancer.
* Peritoneal lesions or large abdominal masses.
* Use of immunosuppressive drugs.
* Inability to temporarily stop chronic anti-coagulation therapy.
* Active bacterial infections with systemic manifestations.
* Active viral infection, including Hepatitis B and Hepatitis C infection. NOTE: Patients with anti-hepatitis B core antibody (HBc) positive, or hepatitis B surface antigen (HBsAg) but DNA negative are allowed exception(s).
* Severe allergic reaction to iodine contrast that cannot be controlled by premedication with antihistamines and steroids.
* History of or known hypersensitivity to melphalan or the components of the melphalan/HDS system.
* History of known hypersensitivity to heparin or the presence of heparin-induced thrombocytopenia.
* Uncontrolled endocrine disorder including diabetes mellitus, hypothyroidism, or hyperthyroidism.
* Received anti-cancer therapy including radiotherapy or investigational agent for any indication ≤ 30 days prior to randomization
* Previous treatment with trifluridine-tipiracil.
* History of allergic reactions attributed to compounds of similar composition to trifluridine/tipiracil or any of its excipients.
* Hereditary problems of galactose intolerance, total lactase deficiency or glucosegalactose malabsorption.
* History of allergic reactions or hypersensitivity to bevacizumab or any of its excipients.
* History of hypersensitivity to Chinese Hamster Ovary cell products or other recombinant human or humanized antibodies.
* Contraindications to bevacizumab, including uncontrolled hypertension, history of active fistula or bowel perforation (unless in the setting of a resected primary), history of CVA or arterial thrombotic event in the last 1 year, or history of venous thrombotic event in the last 30 days.
* Evidence of hepatic vein or portal vein thrombosis
* Prior chemoembolization or radioembolization to the liver or prior hepatic arterial infusion therapy

Contacts and Locations

Study Contact

Matthew Cooney, MD

CONTACT

216-374-8221

MedicalMonitoring@delcath.com

Principal Investigator

Marwan Fakih, MD

PRINCIPAL_INVESTIGATOR

City of Hope Comprehensive Cancer Center

Study Locations (Sites)

City of Hope

Duarte, California, 91010

United States

Collaborators and Investigators

Sponsor: Delcath Systems Inc.

Marwan Fakih, MD, PRINCIPAL_INVESTIGATOR, City of Hope Comprehensive Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-08-05

Study Completion Date2027-10

Study Record Updates

Study Start Date2025-08-05

Study Completion Date2027-10

Terms related to this study

Keywords Provided by Researchers

melphalan/HDS
melphalan/hepatic delivery system
trifluridine-tipiracil
trifluridine-tipiracil (FTD-TPI)
trifluridine-tipiracil (FTD-TPI) plus bevacizumab
trifluridine-tipiracil plus bevacizumab
hepatic delivery system
melphalan
liver dominant disease
colorectal cancer
metastatic colorectal cancer
refractory metastatic colorectal cancer
rectal cancer

Additional Relevant MeSH Terms

Refractory Metastatic Colorectal Cancer