Randomized Study to Evaluate Melphalan/HDS Treatment Followed by Treatment with Eribulin or Vinorelbine or Capecitabine Versus Eribulin or Vinorelbine or Capecitabine Alone in Patients with Metastatic Breast Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Delcath Systems Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

31 Mar 2026 → ongoing

Decision date (initial)

2026-02-04

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Delcath Systems, Inc.

External identifiers

EU CT number

2025-521966-91-00

ClinicalTrials.gov

NCT06875128

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the effect of Melphalan/HDS followed by physicians’ choice of eribulin or vinorelbine or capecitabine on hepatic progression free survival (hPFS) compared to that of eribulin or vinorelbine or capecitabine alone in patients with liver dominant metastatic breast cancer (MBC).

Secondary objectives 4

1. To further evaluate the anti-tumor efficacy of Melphalan/HDS followed by eribulin or vinorelbine or capecitabine compared to eribulin or vinorelbine or capecitabine alone in patients with liver dominant MBC
2. To evaluate the safety and tolerability of Melphalan/HDS followed by eribulin or vinorelbine or capecitabine compared to eribulin or vinorelbine or capecitabine alone in patients with liver dominant MBC
3. To characterize the local and systemic exposure of melphalan administered by the hepatic delivery system (HDS)
4. To assess biomarkers predictive of clinical response to melphalan/HDS in patients with liver-dominant metastatic breast cancer, and to provide mechanistic insights of how high-dose chemotherapy treatment of liver metastases could affect systemic immune function

Conditions and MedDRA coding

Refractory Metastatic Breast Cancer with Liver Dominant Disease

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 20

1. Patient is ≥ 18 years of age on day of consent
2. Histologically confirmed diagnosis of MBC
3. Patients with HER2-negative (IHC 0 or 1+ or 2+ and ISH non-amplified) MBC (including triple negative disease)
4. Patient with Hormone Receptor-Positive disease has progressed on or intolerant of prior endocrine therapy and CDK 4/6 inhibitors
5. 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
6. Patient with HER2-negative breast cancer suitable for single agent chemotherapy as per judgement of treating investigator
7. Patient is a suitable candidate for treatment with one of the following: eribulin, vinorelbine, or capecitabine as per judgement of treating investigator
8. 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 lifethreatening component of the disease is located in the liver
9. MBC metastases must involve ≤ 50% of the liver parenchyma
10. 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, bones and skin
11. Each extrahepatic lesion must not exceed 3 cm in diameter and the total diameter of all extrahepatic lesions must not exceed 20 cm. Additionally, the maximum diameter of tumor lesions within each specific organ cannot be greater than 5 cm. Bone disease is allowed but is excluded from the extrahepatic tumor burden threshold
12. Disease in the liver must be measurable (per RECIST v1.1 guidelines) by computed tomography (CT) and/or magnetic resonance imaging (MRI)
13. Patient weighs ≥ 35 kg (due to possible size limitations with respect to percutaneous catheterization of the femoral artery and vein required with Melphalan/HDS)
14. 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
15. Patient has an ECOG PS of 0-1
16. Patient has adequate hepatic function documented within 14 days prior to randomization: total serum bilirubin ≤1.5 x the upper limit of normal (ULN), prothrombin time (PT) within 2 seconds of the ULN, and aspartate aminotransferase/alanine aminotransferase (AST/ALT) ≤ 5 x ULN. Patient with a documented diagnosis of Gilbert’s syndrome may be eligible with total bilirubin ≤ 3.0 × ULN and direct (conjugated) bilirubin ≤ 1.5 × ULN
17. Patient has the following documented within 14 days prior to randomization: platelet count > 100,000/μL; hemoglobin ≥ 9 gm/dL; white blood cell count (WBC) > 2,000/ μL; absolute neutrophil count ≥ 1.5 x 109/L; and creatinine clearance > 50 mL/min/ (as determined by the Cockcroft-Gault formula)
18. Woman of childbearing potential (WOCBP) (i.e., fertile meaning not permanently sterilized and having had a menstrual period within the past 12 months), should have a negative serum pregnancy test (β-human chorionic gonadotropin) within 7 days prior to randomization
19. If patient is a WOCBP or fertile male (not permanently sterile by bilateral orchiectomy), they or their partner must be willing to use a highly effective contraception method (e.g., combined hormonal contraception; progestogenonly hormonal contraception; intrauterine device, intrauterine hormonereleasing system; bilateral tubal occlusion, vasectomized partner or sexual abstinence) from consent to at least 6 months after the last administration of study treatment. Additionally, WOCBP using hormonal contraception must be willing to add a barrier contraception method, and fertile males must be willing to use a condom
20. Signed informed consent

Exclusion criteria 26

1. Prior chemoembolization or radioembolization to the liver or prior hepatic arterial infusion therapy.
2. Patient has evidence of clinically significant portal hypertension by history, endoscopy, or radiologic studies (large abdominal varices, prior history of varices by endoscopy).
3. Patient has 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.
4. Patient has history or evidence of clinically significant pulmonary disease that precludes the use of general anesthesia.
5. Patient has a history of bleeding disorders, presence of brain metastases or other intracranial abnormalities that would put them at risk for bleeding with anti-coagulation.
6. Patient has known varices at risk of bleeding, including medium or large esophageal or gastric varices, active peptic ulcer, or history of recent hemoptysis.
7. Patient has 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.
8. Patients with 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.
9. Patient is pregnant or breastfeeding.
10. Patient is a 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.
11. Patient requires chronic use of immunosuppressive drugs. NOTE: Oral prednisolone ≤ 10 mg/day or equivalent is allowed.
12. Patient is unable to be temporarily removed from chronic anti-coagulation therapy.
13. Patient has active bacterial infections with systemic manifestations (malaise, fever, leukocytosis).
14. Patient has 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).
15. Patient has known severe allergic reaction to iodine contrast that cannot be controlled by premedication with antihistamines and steroids.
16. Patient has a history of or known hypersensitivity to melphalan or the components of the Melphalan/HDS system.
17. Patient has known latex allergy.
18. Patient has a history of known hypersensitivity to heparin or the presence of heparininduced thrombocytopenia.
19. Patient has an uncontrolled endocrine disorder including diabetes mellitus, hypothyroidism, or hyperthyroidism.
20. Patient received anti-cancer therapy including radiotherapy or investigational agent for any indication ≤ 30 days prior to randomization.
21. Patients should have recovered to Grade 1 or less for AEs related to prior treatment unless deemed clinically not significant, such as lymphopenia, anemia, or grade 2 neuropathy due to prior taxane treatment. NOTE: Certain side effects that are unlikely to develop into serious or life–threatening events (e.g., alopecia) are allowed at ≥ Grade 1.
22. Patient is < 28 days after surgery and surgical wound is not fully healed.
23. Patient is currently under treatment for cancer other than MBC or is not deemed to be cancer free.
24. Patient is not eligible to receive either eribulin or vinorelbine or capecitabine.
25. Albumin level < 3.0 g/dL.
26. Patient has been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Hepatic progression free survival (hPFS)

Secondary endpoints 8

1. Progression free survival (PFS)
2. Overall response rate (ORR) (complete response [CR] + partial response [PR])
3. Hepatic ORR (hORR)
4. Duration of response (DOR)
5. Hepatic DOR (hDOR)
6. Disease control rate (DCR)
7. Hepatic DCR (hDCR)
8. Overall survival (OS)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Delcath Systems Inc.

Sponsor organisation

Delcath Systems Inc.

Address

566 Queensbury Avenue

City

Queensbury

Postcode

12804

Country

United States

Scientific contact point

Organisation

Delcath Systems Inc.

Contact name

Ashleigh Lamson

Public contact point

Organisation

Delcath Systems Inc.

Contact name

Ashleigh Lamson

Third parties 7

Locations

2 EU/EEA countries · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 17 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications