malignant cancer of the eye uveal melanoma
Conditions
Interventions
Uveal melanoma patients will undergo 2 percutaneous hepatic perfusion
procedures with or without 4 courses of the combination of ipilimumab and
nivolumab according to the schedule described in the c
Sponsors
Leids Universitair Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Age between 18-80 years World Health Organization (WHO) Performance Status 0 or I 50% or less histologically or cytologically confirmed unresectable metastatic uveal melanoma in the parenchyma of the liver Hepatic metastases, confined to or predominantly in the liver No prior systemic treatment (including chemotherapy, vaccine therapy, monoclonal Ab treatment, IL-2) Local pre-treatment of uveal melanoma metastases is allowed (resection and/or thermal ablation), except for chemotherapy containing procedures (e.g. chemoembolization) and radio-embolization, and as long as patients have progressed with measurable disease according to RECIST 1.1 No concurrent systemic immunosuppressive medications >= 10mg/day prednisone or equivalent. Topical, inhaled, nasal and ophthalmic steroids, and adrenal replacement therapy are allowed. 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 2 years. No aberrant vascular anatomy of the liver that precludes PHP
Exclusion criteria
Exclusion criteria: Cerebral or meningeal metastasized uveal melanoma Subjects with any active autoimmune disease or a documented history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications, except for subjects with vitiligo or resolved childhood asthma/atopy Prior immunotherapy (tumor vaccine, cytokine, or growth factor) Known history of infection with Human Immunodeficiency Virus; Active infection requiring therapy, positive serology for Hepatitis B surface antigen and/or Hepatitis C ribonucleic acid (RNA) History of congestive heart failure, active cardiac conditions, including unstable coronary syndromes (unstable or severe angina, recent myocardial infarction), significant arrhythmias and severe valvular disease must be evaluated for risks of undergoing general anesthesia. History or evidence of clinically significant pulmonary disease e.g. severe COPD that precludes the use of general anesthesia. Underlying medical conditions that, in the Investigator's opinion, will make the administration of study treatment hazardous or obscure the interpretation of toxicity determination or adverse events; Latex allergy, and known hypersensitivity/allergy to ipilimumab, nivolumab, melphalan or heparin Prior Whipple*s Surgery Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids History of or current immunodeficiency disease, splenectomy or splenic irradiation; prior allogeneic stem cell transplantation Patients who are unable to be temporarily removed from chronic anti-coagulation therapy Patients with active bacterial infections with systemic manifestations (malaise, fever, leucocytosis) are not eligible until completion of appropriate therapy Use of other investigational drugs before study drug administration for systemic malignancy Pregnancy or nursing
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 1: To determine safety and tolerability, dose limiting toxicities (DLTs), maximum tolerated dose (MTD) and recommended phase II dose (RPTD) of the combination of ipilimumab plus nivolumab and PHP in patients with unresectable, histologically confirmed metastases of uveal melanoma. Phase 2: To determine the efficacy of PHP alone versus the combination of PHP with ipilimumab/nivolumab will be determined in the randomized phase II study. | — |
Secondary
| Measure | Time frame |
|---|---|
| - 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. - To evaluate overall survival of patients treated with PHP alone versus patients with the combination of PHP with ipilimumab and nivolumab. | — |
Countries
Netherlands
Outcome results
None listed