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 Breast Cancer w/Liver Dominant Disease

NCT06875128 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: PHP-MBC-202
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 2

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 breast 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 cycles of 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 8 weeks

Conditions

Metastatic Breast Cancer in the Liver

Keywords

melphalan; melphalan/HDS; melphalan/hepatic delivery system; eribulin; vinorelbine; capecitabine; metastatic breast cancer; MBC; liver dominant disease; metastatic breast cancer in the liver; hepatic delivery system; PHP; HER2-negative breast cancer; HER-2 negative; Hormone Receptor-Positive disease

Outcome Measures

Primary Outcomes (1)

• hPFS

  Hepatic Progression Free Survival

  assessed through study completion, an average of 2 years

Secondary Outcomes (8)

• PFS

  assessed through study completion, an average of 2 years

• ORR

  Baseline through completion of treatment, assessed through study completion, an average of 2 years

• hORR

  assessed through study completion, an average of 2 years

• DOR

  assessed through study completion, an average of 2 years

• hDOR

  assessed through study completion, an average of 2 years

Other Outcomes (2)

• Safety and Tolerability

  assessed through study completion, an average of 2 years

• Pharmacokinetic Endpoint

  assessed through study completion, an average of 2 years

Study Arms (2)

Melphalan/HDS followed by Physician's choice of SOC (eribulin, vinorelbine, or capecitabine)

EXPERIMENTAL

Melphalan/HDS is given as an infusion of Melphalan into the hepatic artery under general anesthesia. This treatment is administered then followed by Physician's choice of SOC (eribulin, vinorelbine, or capecitabine) then repeated for a second cycle of Melphanlan/HDS followed by Physician's choice of SOC.

Drug: Melphalan/HDS followed by Physician's choice of SOC (eribulin, vinorelbine, or capecitabine)

Physician's choice of SOC (eribulin, vinorelbine, or capecitabine) Alone

ACTIVE COMPARATOR

Physician's choice of SOC (eribulin, vinorelbine, or capecitabine)

Drug: Physician's choice of SOC (eribulin, vinorelbine, or capecitabine)

Interventions

Melphalan/HDS followed by Physician's choice of SOC (eribulin, vinorelbine, or capecitabine) DRUG

Melphalan/HDS followed by Physician's choice of SOC (eribulin, vinorelbine, or capecitabine)

Melphalan/HDS followed by Physician's choice of SOC (eribulin, vinorelbine, or capecitabine)

Physician's choice of SOC (eribulin, vinorelbine, or capecitabine) DRUG

Physician's choice of SOC (eribulin, vinorelbine, or capecitabine)

Physician's choice of SOC (eribulin, vinorelbine, or capecitabine) 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 MBC.
• Patients with HER2-negative (IHC 0 or 1+ or 2+ and ISH non-amplified) MBC (including triple negative disease).
• Patient with Hormone Receptor-Positive disease has progressed on or intolerant of prior endocrine therapy and CDK 4/6 inhibitors.
• Disease progression after TOPO-1 isomerase inhibitor payload ADC, such as sacituzumab govitecan and/or trastuzumab deruxtecan. Patients not eligible or suitable for ADCs can be considered for this study. NOTE: In jurisdictions where those ADCs are not available as standard of care, patients will be eligible after prior treatment or intolerable toxicity on two standard chemotherapy regimens for the appropriate disease subtype.
• Patient with HER2-negative breast cancer suitable for single agent chemotherapy as per judgement of treating investigator.
• Patient is a suitable candidate for treatment with one of the following: eribulin, vinorelbine, or capecitabine as per judgement of treating investigator.
• Patient has liver dominant metastatic disease. Liver-dominant is defined as the majority of total tumor burden is located in the liver, and/or the life-threatening component of the disease is located in the liver.
• MBC metastases must involve ≤ 50% of the liver parenchyma.
• If there is evidence of extrahepatic metastatic disease, it is limited, and the life-threatening component of disease is in the liver. Extrahepatic disease is restricted to lesions in the breast, lung, other visceral organs, lymph nodes and skin.
• Disease in the liver must be measurable (per RECIST v1.1 guidelines) by computed tomography (CT) and/or magnetic resonance imaging (MRI).
• Patient weighs ≥ 35 kg
• 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.
• Patient has an ECOG PS of 0-1.

You may not qualify if:

• Prior chemoembolization or radioembolization to the liver or prior hepatic arterial infusion therapy.
• 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 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.
• An active second malignancy or has a history of recent definitively treated invasive cancer within 2 years prior to enrolment. Exceptions are optimally treated and controlled basal cell carcinoma, other skin cancers, thyroid cancer.
• Symptoms and signs indicating clinically significant progression of disease including cord compression, increasing pain symptoms, increasing oxygen requirements, impending pathological fracture, compressive lymphadenopathy, or symptomatic pleural effusion.
• Pregnant or breastfeeding.
• WOCBP (i.e., fertile meaning not permanently sterilized and having had a menstrual period within the past 12 months) who is unable to undergo hormonal suppression to avoid menstruation during treatment.
• Patient requires chronic use of immunosuppressive drugs. NOTE: Oral prednisolone ≤ 10 mg/day or equivalent is allowed.
• Unable to be temporarily removed from chronic anti-coagulation therapy.
• Active bacterial infections with systemic manifestations (malaise, fever, leucocytosis).
• An active 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).
• Known severe allergic reaction to iodine contrast that cannot be controlled by premedication with antihistamines and steroids.

Sponsors & Collaborators

• Delcath Systems Inc.: lead

Study Sites (2)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Ohio State University, Stefanie Spielman Comprehensive Breast Center

Columbus, Ohio, 43212, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

eribulin; Vinorelbine; Capecitabine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

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: March 6, 2025
• First Posted: March 13, 2025
• Study Start: January 29, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): August 1, 2029
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)