Understanding How Your Immune System Responds to a Targeted Liver Cancer Treatment
Evaluating Immune Response to Percutaneous Hepatic Perfusion With Melphalan for the Treatment of Ocular Melanoma Metastatic to the Liver
In Plain English
This study is for people with uveal melanoma (eye cancer) that has spread to the liver. Researchers want to understand how your body's immune system reacts to a specific treatment called Percutaneous Hepatic Perfusion (PHP) with melphalan—a chemotherapy drug delivered directly to your liver. Here's what happens: Before treatment, doctors will take a small tissue sample (biopsy) from your liver and draw blood to see what your immune system looks like at the start. Then you'll receive melphalan through PHP, which is a procedure that sends the chemotherapy directly into the blood vessels feeding your liver tumor, so the drug concentrates where it's needed most. About 3-4 weeks later, you'll come back for another liver biopsy and blood draw. By comparing your 'before' and 'after' samples, researchers can see how your immune cells changed and responded to the treatment. This research helps doctors understand whether PHP with melphalan not only shrinks tumors but also activates your immune system to fight the cancer. You're contributing to knowledge that could help future patients with the same diagnosis.
What This Trial Does
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.
How It Works
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.
Who Can Join
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.
Treatments
Melphalan through Percutaneous Hepatic Perfusion (DRUG)
Melphalan through Percutaneous Hepatic Perfusion will be received as standard of care,
Trial Sites (1)
Massachusetts General Hospital
Boston, Massachusetts, United States
Recruiting