Immune response after delivering melphalan directly to the liver for uveal (eye) melanoma that has spread to the liver.
Evaluating Immune Response to Percutaneous Hepatic Perfusion With Melphalan for the Treatment of Ocular Melanoma Metastatic to the Liver
This test will see how the liver's immune system responds when people with uveal melanoma that has spread to the liver receive melphalan delivered directly to the liver through percutaneous hepatic perfusion.
Quick facts
| Phase | Not applicable |
|---|---|
| Study type | Interventional |
| Enrollment | 10 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Massachusetts General Hospital Academic / other |
| Drugs / interventions | Crizotinib, radiation, methotrexate, cyclophosphamide, prednisone, chemotherapy |
| Locations | 1 site (Boston, Massachusetts) |
| Trial ID | NCT07364474 on ClinicalTrials.gov |
What this trial studies
Participants will have baseline liver biopsies and blood drawn before receiving a single dose of melphalan delivered via percutaneous hepatic perfusion (PHP). They will return 21–28 days after treatment for a follow-up liver biopsy and peripheral blood draw. Researchers will compare baseline and post-treatment samples to characterize changes in immune cell populations and signaling within the liver microenvironment. The goal is to map the local and systemic immune response to focused hepatic chemotherapy.
Who should consider this trial
Good fit: Adults with histologically confirmed uveal melanoma metastatic to the liver who are eligible for percutaneous hepatic perfusion, have at least one liver lesion ≥1 cm amenable to biopsy, acceptable lab values, ECOG 0–1, and life expectancy over 12 weeks.
Not a fit: Patients who are not candidates for PHP, have diffuse liver involvement not suitable for biopsy, poor performance status, or inadequate blood counts are unlikely to receive benefit from participation.
Why it matters
Potential benefit: If successful, the results could identify immune changes that help guide future liver-directed or combination immunotherapy approaches for uveal melanoma metastases.
How similar studies have performed: Percutaneous hepatic perfusion with melphalan has shown local tumor control in prior clinical use, but prospectively measuring the liver immune response before and after PHP is relatively novel and not well established.
Eligibility criteria
Show full inclusion / exclusion criteria
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.
Where this trial is running
Boston, Massachusetts
- Massachusetts General Hospital — Boston, Massachusetts, United States (Recruiting)
Study contacts
- Principal investigator: Eric Wehrenberg-Klee, MD — Massachusetts General Hospital
- Study coordinator: Aleigha Lawless
- Email: alawless@mgb.org
- Phone: 617-643-3578
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.