Recruiting
Phase 2

Liver-Directed Therapy

Sponsor:

Delcath Systems Inc.

Code:

NCT06607458

Conditions

Refractory Metastatic Colorectal Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Melphalan/HDS Followed by Consolidation Treatment with Trifluridine-tipiracil plus Bevacizumab

Trifluridine-tipiracil plus Bevacizumab Alone

Study Details

Brief summary:

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

Conditions

Refractory Metastatic Colorectal Cancer

Study ID

NCT06607458

Start date

Aug 5, 2025

Status verified date

May, 2026

Completion date

Oct, 2027

Anticipated

Primary completion date

Dec, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion 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.

Exclusion Criteria:

  • 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

Study Design

Enrollment

90 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Melphalan/HDS followed by Consolidation Treatment with Trifluridine-tipiracil plus Bevacizumab

Melphalan/HDS is given as an infusion of Melphalan into the hepatic artery under general anesthesia. This treatment is administered twice, 8 weeks apart. Following 2 treatments with Melphalan/HDS, Trifluridine-tipiracil is given 35 mg/m2 up to a maximum of 80 mg per dose orally twice daily with food on Days 1 through 5 and Days 8 through 12 of each 28-day cycle; and intravenous (IV) bevacizumab 5 mg/kg body weight on Days 1 and 15 of each 28-day cycle until disease progression or unacceptable toxicity

active comparator: Trifluridine-tipiracil plus Bevacizumab Alone

Trifluridine-tipiracil plus Bevacizumab is the standard of care for patients with metastatic colorectal cancer. Trifluridine-tipiracil is given 35 mg/m2 up to a maximum of 80 mg per dose orally twice daily with food on Days 1 through 5 and Days 8 through 12 of each 28-day cycle; and intravenous (IV) bevacizumab 5 mg/kg body weight on Days 1 and 15 of each 28-day cycle until disease progression or unacceptable toxicity

Interventions

Melphalan/HDS Followed by Consolidation Treatment with Trifluridine-tipiracil plus Bevacizumab

Trifluridine-tipiracil plus Bevacizumab Alone

Trifluridine-tipiracil plus Bevacizumab Alone

Trifluridine-tipiracil plus Bevacizumab Alone

Primary outcome measure

  • hPFS [ Time Frame: time from randomization to the first occurrence of hepatic disease progression, assessed over 24 months ]

Central Contacts and Locations

Central contacts

Matthew Cooney, MD

216-374-8221MedicalMonitoring@delcath.com

Locations

City of Hope

Recruiting

Duarte, California, United States, 91010

UCLA Hematology/Oncology-Santa Monica

Recruiting

Santa Monica, California, United States, 90404

Moffitt Cancer Center

Recruiting

Tampa, Florida, United States, 33612

The University of Kansas Clinical Research Center

Recruiting

Fairway, Kansas, United States, 66205

Ochsner Clinic Foundation

Recruiting

New Orleans, Louisiana, United States, 70121

Huntsman Cancer Institute, University of Utah

Recruiting

Salt Lake City, Utah, United States, 84112

More Information

Sponsor

Delcath Systems Inc.

Last update posted

Jun 1, 2026

Last verified

May, 2026

Keywords

  • 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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Delcath Systems Inc. on 2026-06-01.