ipilimumab for Metastatic uveal melanoma

Inclusion criteria

• {"criterion_text":"- Age between 18-80 years"}
• {"criterion_text":"- World Health Organization (WHO) Performance Status 0 or I"}
• {"criterion_text":"- 50% or less histologically or cytologically confirmed unresectable metastatic uveal melanoma in the parenchymaof the liver"}
• {"criterion_text":"- Hepatic metastases, confined to or predominantly in the liver"}
• {"criterion_text":"- No prior systemic treatment (including chemotherapy, vaccine therapy, monoclonal Ab treatment, IL-2)"}
• {"criterion_text":"- Local pre-treatment of uveal melanoma metastases is allowed (resection and/or thermal ablation), except forchemotherapy containing procedures (e.g. chemoembolization) and radio-embolization, and as long as patientshave progressed with measurable disease according to RECIST 1.1"}
• {"criterion_text":"- No concurrent systemic immunosuppressive medications ≥ 10mg/day prednisone or equivalent. Topical, inhaled,nasal and ophthalmic steroids, and adrenal replacement therapy are allowed."}
• {"criterion_text":"- Screening laboratory values must meet the following criteria: WBC ≥ 2.0x109/L, Neutrophils ≥ 1.0x109/L, Platelets≥ 100 x109/L, Hemoglobin ≥ 6.5 mmol/L, Creatinine ≤ 2x ULN, AST ≤ 2.5 x ULN, ALT ≤ 2.5 x ULN, Total bilirubin ≤1.5 X ULN, INR and PTT ≤ 1.5 x ULN, LDH <2xULN"}
• {"criterion_text":"- Women of child bearing potential (WOCBP) must agree to use a reliable form of contraceptive as described in theresearch protocol"}
• {"criterion_text":"- Men must agree to the use of male contraception as described in the research protocol"}
• {"criterion_text":"- Absence of additional severe and/or uncontrolled concurrent disease"}
• {"criterion_text":"- No prior, or ongoing other malignancy, except adequately treated basal cell or squamous cell skin cancer, cervicalcancer in situ or adequately treated other cancer with eradicative intent for which the patient has beencontinuously disease-free for >2 years."}
• {"criterion_text":"- No aberrant vascular anatomy of the liver that precludes PHP"}

Exclusion criteria

• {"criterion_text":"- Cerebral or meningeal metastasized uveal melanoma"}
• {"criterion_text":"- Subjects with any active autoimmune disease or a documented history of autoimmune disease, or history ofsyndrome that required systemic steroids or immunosuppressive medications, except for subjects with vitiligo orresolved childhood asthma/atopy"}
• {"criterion_text":"- Prior immunotherapy (tumor vaccine, cytokine, or growth factor)"}
• {"criterion_text":"- Known history of infection with Human Immunodeficiency Virus"}
• {"criterion_text":"- Active infection requiring therapy, positive serology for Hepatitis B surface antigen and/or Hepatitis C ribonucleicacid (RNA)"}
• {"criterion_text":"- History of congestive heart failure, active cardiac conditions, including unstable coronary syndromes (unstable orsevere angina, recent myocardial infarction), significant arrhythmias and severe valvular disease must beevaluated for risks of undergoing general anesthesia"}
• {"criterion_text":"- History or evidence of clinically significant pulmonary disease e.g. severe COPD that precludes the use of generalanesthesia"}
• {"criterion_text":"- Underlying medical conditions that, in the Investigator's opinion, will make the administration of study treatmenthazardous or obscure the interpretation of toxicity determination or adverse events"}
• {"criterion_text":"- Latex allergy, and known hypersensitivity/allergy to ipilimumab, nivolumab, melphalan or heparin"}
• {"criterion_text":"- Prior Whipple’s Surgery"}
• {"criterion_text":"- Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids"}
• {"criterion_text":"- History of or current immunodeficiency disease, splenectomy or splenic irradiation"}
• {"criterion_text":"- prior allogeneic stem celltransplantation"}
• {"criterion_text":"- Patients who are unable to be temporarily removed from chronic anti-coagulation therapy"}
• {"criterion_text":"- Patients with active bacterial infections with systemic manifestations (malaise, fever, leucocytosis) are not eligibleuntil completion of appropriate therapy"}
• {"criterion_text":"- Use of other investigational drugs before study drug administration for systemic malignancy"}
• {"criterion_text":"- Pregnancy or nursing"}

Primary endpoints

• {"endpoint_text":"- Safety and feasibility of combining percutaneous hepatic perfusion with ipilimumab and nivolumab (phase 1b part).","definition_or_measurement_approach":"Assess safety and feasibility including determination of dose limiting toxicities (DLTs), maximum tolerated dose (MTD) and recommended phase II dose (RPTD) for the combination (as described in main objective)."}
• {"endpoint_text":"- Efficacy as measured by progression-free survival at one year comparing PHP alone versus patients with the combination of PHP with ipilimumab and nivolumab (randomized phase 2 part).","definition_or_measurement_approach":"Progression-free survival (PFS) at one year comparing PHP alone versus PHP + ipilimumab + nivolumab (PFS at 12 months is the measurement timepoint)."}

Secondary endpoints

• {"endpoint_text":"- To evaluate best overall response rate according to RECIST 1.1 and iRECIST of patients treated with PHP alone versus patients with the combination of PHP with ipilimumab and nivolumab.","definition_or_measurement_approach":"Best overall response rate assessed by RECIST 1.1 and iRECIST criteria."}
• {"endpoint_text":"- To evaluate overall survival of patients treated with PHP alone versus patients with the combination of PHP with ipilimumab and nivolumab.","definition_or_measurement_approach":"Overall survival (OS) measured as time from randomization/enrolment to death from any cause."}

Netherlands

Earliest CTIS Part Ii Submission Date

12-09-2024

Latest Decision Or Authorization Date

12-09-2024

Number Of Sites

1

Number Of Participants

88

Primary sponsor

Full Name

Leids Universitair Medisch Centrum (LUMC)

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands