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

NCT06607458 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: PHP-CRC-201
• Study Type: interventional
• Target: 90
• Locations: 6 countries
• Sites: 10

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

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

Outcome Measures

Primary Outcomes (1)

• hPFS

  Hepatic Progression Free Survival

  time from randomization to the first occurrence of hepatic disease progression, assessed over 24 months

Secondary Outcomes (8)

• PFS

  time from randomization to the first occurrence of progression, assessed up to 24 months

• OS

  time from randomization date to the date of death due to any cause, assessed up to 36 months

• ORR

  Baseline through completion of treatment, assessed up to 24 months

• hORR

  assessed from Baseline until there is evidence of disease progression in the liver, assessed up to 24 months

• DOR

  assessed from Baseline until there is evidence of disease progression, assessed up to 24 months

Other Outcomes (1)

• Safety and Tolerability

  assessed from signed informed consent form until study completion

Study Arms (2)

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

EXPERIMENTAL

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

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

Trifluridine-tipiracil plus Bevacizumab Alone

ACTIVE COMPARATOR

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

Drug: Trifluridine-tipiracil plus Bevacizumab Alone

Interventions

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

Trifluridine-tipiracil plus Bevacizumab Alone

Also known as: Melphalan, HDS, Trifluridine-tipiracil plus Bevacizumab, Trifluridine-tipiracil, Melphalan/HDS

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

Trifluridine-tipiracil plus Bevacizumab Alone DRUG

Trifluridine-tipiracil plus Bevacizumab Alone

Also known as: Trifluridine-tipiracil, Bevacizumab

Trifluridine-tipiracil plus Bevacizumab Alone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Delcath Systems Inc.: lead

Study Sites (10)

City of Hope

Duarte, California, 91010, United States

RECRUITING

UCLA Hematology/Oncology-Santa Monica

Santa Monica, California, 90404, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

The University of Kansas Clinical Research Center

Fairway, Kansas, 66205, United States

RECRUITING

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah, 84112, United States

RECRUITING

Czech Republic - University Hospital

Prague, Czechia

RECRUITING

Helios Park-Klinikum Leipzig

Leipzig, Germany

RECRUITING

Instiuto Europeo de Oncologia

Milan, Italy

RECRUITING

Clinical Hospital Center "Bezanijska Kosa"

Belgrade, 11080, Serbia

RECRUITING

Hospital Clinic Barcelona

Barcelona, Spain

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms; Rectal Neoplasms

Interventions

trifluridine tipiracil drug combination; Bevacizumab; Melphalan

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids

Study Officials

• Marwan Fakih, MD

  City of Hope Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Matthew Cooney, MD

CONTACT

216-374-8221; MedicalMonitoring@delcath.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2024
• First Posted: September 23, 2024
• Study Start: August 5, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): October 1, 2027
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1); ES (1); CZ (1); DE (1); IT (1); US (5)