Uveal MelanomaNCT07364474
Immune Response to Percutaneous Hepatic Perfusion With Melphalan for Ocular Melanoma Metastatic to the Liver
A study testing Melphalan through Percutaneous Hepatic Perfusion and Melphalan through Percutaneous Hepatic Perfusion in combination with Ipilimumab and Nivolumab in people with Uveal Melanoma, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
This study seeks to better understand the liver's immune response to receiving chemotherapy agent melphalan through Percutaneous Hepatic Perfusion (PHP) alone or in combination with Ipilimumab and Nivolumab for patients with Uveal Melanoma that has metastasized to the liver. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Uveal Melanoma
- What is being tested?
- Melphalan through Percutaneous Hepatic Perfusion and Melphalan through Percutaneous Hepatic Perfusion in combination with Ipilimumab and Nivolumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Jan 2026to Sep 2028
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- In Cohort B only: patient is determined to be a candidate for percutaneous hepatic perfusion with melphalan combined with Ipilimumab and Nivolumab
- 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
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- 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
Who cannot join
- 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
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- 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.
- Prior 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Juliane A Andrade Czapla contact
United States1 site, 1 recruiting
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: 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) alone or in combination with Ipilimumab and Nivolumab for patients with Uveal Melanoma that has metastasized to the liver.
Read the detailed description
Biopsies and blood samples will be collected before treatment to establish baseline measurements. Patients will then receive either a single dose of Melphalan via Percutaneous Hepatic Perfusion (PHP) or a single dose of Melphalan via Percutaneous Hepatic Perfusion (PHP) in combination with Ipilimumab and Nivolumab per standard of care 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.
- Conditions
- Uveal Melanoma
- Being tested
- Melphalan through Percutaneous Hepatic Perfusion, Melphalan through Percutaneous Hepatic Perfusion in combination with Ipilimumab and Nivolumab
- Keywords
- Uveal Melanoma, Uveal Melanoma, Metastatic, Uveal Melanoma, Metastatic to liver
- Medical subject headings
- Uveal Melanoma, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Melphalan through Percutaneous Hepatic PerfusionDrug
Melphalan through Percutaneous Hepatic Perfusion will be received as standard of care.
Melphalan through Percutaneous Hepatic Perfusion in combination with Ipilimumab and NivolumabDrug
Melphalan through Percutaneous Hepatic Perfusion in combination with Ipilimumab and Nivolumab will be received as standard of care.
| Study group | Role | What they receive |
|---|---|---|
| Melphalan through Percutaneous Hepatic Perfusion (PHP) | Active comparator | Participants will receive PHP alone per standard of care. Receives: Drug: Melphalan through Percutaneous Hepatic Perfusion |
| Melphalan through Percutaneous Hepatic Perfusion (PHP) in Combination with Ipilimumab and Nivolumab | Active comparator | Participants will receive PHP in combination with Ipilimumab and Nivolumab per standard of care. Receives: Drug: Melphalan through Percutaneous Hepatic Perfusion in combination with Ipilimumab and Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intratumoral CXCL13⁺ CD8⁺ T-cell infiltration following Percutaneous Hepatic Perfusion (PHP) or Percutaneous Hepatic Perfusion (PHP) in combination with Ipilimumab and Nivolumab.
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.
Measured: 3-4 weeks post treatment
Secondary outcomes (5)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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 .
Measured: 28-42 days post treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2026
- Study start27 Jan 2026
- Primary completionDec 2027 (estimated)
- Study completionSep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Uveal MelanomaStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- A total of 20 participants are expected to enroll in the study, with 10 participants in each arm. Participants in Arm A will receive PHP monotherapy, while participants in Arm B will receive PHP in combination with Ipilimumab and Nivolumab. Treatment in both arms will be administered according to the standard of care. Treatment arm selection will be at the treating physician's discretion, taking into consideration factors such as the patient's history of prior immunotherapy-related toxicities.
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Eric Wehrenberg-Klee, MD, Massachusetts General Hospital
- Investigators
- Eric Wehrenberg-Klee, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07364474
- Sponsor's protocol ID
- 25-679
- Status last verified
- Oct 2026
- First submitted
- 16 Dec 2025
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.