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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Melphalan through Percutaneous Hepatic Perfusion
  Melphalan through Percutaneous Hepatic Perfusion will be received as standard of care,

Первичные конечные точки

• Intratumoral CXCL13⁺ CD8⁺ T-cell infiltration following Percutaneous Hepatic Perfusion (PHP) [Срок оценки: 3-4 weeks post treatment]

Вторичные конечные точки (5)

• Antigen-presenting cell (APC) populations and their activation state in the tumor microenvironment. [Срок оценки: 28-42 day tumor biopsies]
• T-cell infiltration in tumor and adjacent hepatic parenchyma. [Срок оценки: 28-42 days post treatment]
• Single-cell RNA sequencing derived frequency of macrophages and myeloid-derived suppressor cells (MDSCs) [Срок оценки: 28-42 days post treatment]
• Single-cell RNA sequencing derived phenotype of macrophages and myeloid-derived suppressor cells (MDSCs) [Срок оценки: 28-42 days post treatment]
• Immune cell populations with molecular and biochemical features of tissue and peripheral blood. [Срок оценки: 28-42 days post treatment.]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Другое

Центры проведения

США · 1 центр

• Massachusetts General Hospital — Boston

Идентификаторы

NCT: NCT07364474 · 25-679

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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