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

Korábbi kezelés

• 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
• 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.

Más betegség

• 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.

Laborértékek

• Anticoagulant or anti-platelet medication that cannot be interrupted prior to biopsy
• 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.

Egyéb

• Pregnant or lactating

• 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
• 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