Immune Response to Percutaneous Hepatic Perfusion With Melphalan for Ocular Melanoma Metastatic to the Liver

Evaluating Immune Response to Percutaneous Hepatic Perfusion With Melphalan for the Treatment of Ocular Melanoma Metastatic to the Liver

This study seeks to better understand the liver's immune response to receiving chemotherapy agent melphalan through Percutaneous Hepatic Perfusion (PHP) for patients with Uveal Melanoma that has metastasized to the liver.

Study Overview

• Status: Recruiting
• Conditions: Uveal Melanoma
• Intervention / Treatment: Drug: Melphalan through Percutaneous Hepatic Perfusion

Detailed Description

Biopsies and blood samples will be collected before treatment to establish baseline measurements. Patients will then receive a single dose of Melphalan via Percutaneous Hepatic Perfusion (PHP) and return 21-28 days later for a follow-up biopsy and peripheral blood draw. Baseline and post-treatment samples will be compared to evaluate the immune response.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Aleigha Lawless; Phone Number: 617-643-3578; Email: alawless@mgb.org
• Study Contact Backup: Name: Juliane A Andrade Czapla; Email: jczapla@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient has histologically or cytologically confirmed diagnosis of uveal melanoma metastatic to the liver and is determined to be a candidate for percutaneous hepatic perfusion with melphalan
• The subject has read, signed and dated the Informed Consent Form (ICF), having been advised of the risks and benefits of the trial in a language understood by the subject.
• Age > 18 years at date of informed consent signature having the ability to comply with the protocol.
• Contrast-enhanced cross-sectional imaging of the abdomen (either CT or MRI) obtained within two months prior to study enrollment
• Measurable metastatic disease. Subject must have at least one site of metastatic disease ≥ 1 cm in size and amenable to percutaneous image-guided biopsy
• Life expectancy > 12 weeks.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Laboratory requirements:
• Absolute neutrophil count (ANC) > 1 x 109/L
• Platelets > 75 x 109/L
• Alanine aminotransferase (ALT) / Aspartate aminotransferase (AST) < 5 x ULN
• Total bilirubin <3 mg/dL
• International normalized ratio (INR) <1.7
• Glomerular filtration rate (GFR) >30 ml/min

Exclusion Criteria:

• Lesion to undergo biopsy cannot have undergone prior radiation therapy or other locoregional therapy
• Continued adverse events from a previously administered chemotherapeutic agents. Grade 1 adverse events and ongoing toxicities such as alopecia are exempt
• Treatment with systemic corticosteroids exceeding the equivalent of 10 mg/day of prednisone or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, and anti-tumor necrosis factor [anti-tumor necrosis factor (TNF)] agents) within 2 weeks prior to Day 1, or anticipated requirement for systemic immunosuppressive medications exceeding the equivalent of 10 mg/day of prednisone during the trial
• Patients who receive acute, low-dose, systemic corticosteroid medications (e.g., a one-time dose of dexamethasone for nausea) or for prevention of hypersensitivity reactions to contrast agents may be enrolled in the trial.
• Anticoagulant or anti-platelet medication that cannot be interrupted prior to biopsy
• Pregnant or lactating
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicated the use of an investigational drug or that could affect the interpretation of the results or render the patient at high risk from treatment complications.
• Treatment with systemic immunostimulatory agents (including but not limited to interferon(IFN)s, interleukin [IL]-2) within 6 weeks or five half- lives of the drug, whichever was shorter, prior to Day 1.
• Treatment with immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies, anti-LAG-3 antibodies, within the past three months. Prior treatment with tebentafusp is allowed with no washout period required.
• Treatment with any investigational systemic medication within at least one month prior to biopsy. If an investigational agent is an immune checkpoint inhibitor, a three-month washout is required. Prior treatment with Darovasertib and Crizotinib is allowed with no washout period required.
• Signs or symptoms clinically significant of infection within 2 weeks prior to Day 1.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Melphalan through Percutaneous Hepatic Perfusion; Single arm	Drug: Melphalan through Percutaneous Hepatic Perfusion; Melphalan through Percutaneous Hepatic Perfusion will be received as standard of care,

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intratumoral CXCL13⁺ CD8⁺ T-cell infiltration following Percutaneous Hepatic Perfusion (PHP)	Change in the percentage of CXCL13⁺ CD8⁺ T cells in tumor biopsies between Day 0 (pre-treatment) and Day 28-42 (approximately 3-4 weeks post-treatment), as measured by single-cell RNA sequencing.	3-4 weeks post treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antigen-presenting cell (APC) populations and their activation state in the tumor microenvironment.	Comparison of proportions and activation markers of dendritic cells and other APC subsets in pre-treatment (Day 0) and post-treatment (Day 28-42) tumor biopsies.	28-42 day tumor biopsies
T-cell infiltration in tumor and adjacent hepatic parenchyma.	Change in FOXP3⁺ regulatory T-cell infiltration between pre-treatment (Day 0) and post-treatment (Day 28-42) tumor and parenchymal biopsies.	28-42 days post treatment
Single-cell RNA sequencing derived frequency of macrophages and myeloid-derived suppressor cells (MDSCs)	Change in the frequency of macrophages and myeloid-derived suppressor cells (MDSCs) between pre-treatment (Day 0) and post-treatment (Day 28-42) samples as assessed by single-cell RNA sequencing.	28-42 days post treatment
Single-cell RNA sequencing derived phenotype of macrophages and myeloid-derived suppressor cells (MDSCs)	Change in the phenotype of macrophages and myeloid-derived suppressor cells (MDSCs) between pre-treatment (Day 0) and post-treatment (Day 28-42) samples.	28-42 days post treatment
Immune cell populations with molecular and biochemical features of tissue and peripheral blood.	Correlation between tissue-based immune cell changes and peripheral biomarkers (e.g. cytokine expression (ng/ml), ctDNA (mtm/ml)) assessed at Day 0 and Day 28-42, and with hepatic radiologic response assessed on CT/MRI as per clinical standard of care .	28-42 days post treatment.

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Eric Wehrenberg-Klee, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: December 16, 2025
• First Submitted That Met QC Criteria: January 21, 2026
• First Posted (Actual): January 23, 2026

Study Record Updates

• Last Update Posted (Actual): March 11, 2026
• Last Update Submitted That Met QC Criteria: March 9, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Uveal Melanoma; Uveal Melanoma, Metastatic; Uveal Melanoma, Metastatic to liver
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Eye Diseases; Neoplastic Processes; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Eye Neoplasms; Uveal Diseases; Melanoma; Pathological Conditions, Signs and Symptoms; Uveal Neoplasms; Neoplasm Metastasis; Uveal Melanoma
• Other Study ID Numbers: 25-679

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: alawless@mgb.org . The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: Data can be shared no earlier than 1 year following the date of publication.
• IPD Sharing Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No