Neoadjuvant Ipilimumab and Nivolumab for Patients With High-risk Uveal Melanoma
The goal of this clinical trial is to investigate the safety and feasibility of neoadjuvant immunotherapy for patients with high-risk uveal melanoma. The main question is: \- Is neoadjuvant treatment with nivolumab and ipilimumab safe and feasible for patientt with high-riks uveal melanoma? In addition pathological response, distant metastases-free survival, overall survival and immunological changes in the tumor microenviroenment after therapy will be assesed.
• Age ≥ 18 ≤ 80
• The patient is able to read and understand Danish.
• Primary, localized and treatment-naive uveal melanoma planned for enucleation (high risk/T3-T4) and available for transvitreal biopsies. The initial diagnosis of uveal melanoma is based on ophthalmologic and clinical findings.
• ECOG performance status of 0 or 1 (appendix 2)
• The patient meets the following haematological and biochemical criteria at time of screening: a) AST and ALT ≤2,5 X ULN, b) Serum total bilirubin ≤1,5 X ULN or direct bilirubin ≤ ULN for patient with total bilirubin level \> 1,5 ULN, c) Serum creatinine ≤1,5 X ULN, d) ANC (Absolute Neutrophil Count) ≥1,000/mcL, e) Platelets ≥ 75,000 /mcL, f) Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L
• Signed statement of consent after receiving oral and written study information
• Willingness to participate in the planned treatment and follow-up schedule
• For women of childbearing potential (WOCBP) a negative serum pregnancy test at time of screening and the use of highly effective contraception is required. This applies from screening and until 6 months after treatment.
⁃ The following is considered highly effective methods of contraception: 1. Combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal or transdermal), 2. Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) 3. Intrauterine device (IUD) 4. intrauterine hormone-releasing system (IUS) 5. Bilateral tubal occlusion, 6. Vasectomised partner provided that the vasectomy is confirmed successful, 7. Sexual abstinence defined as refraining from heterosexual intercourse. WOCBP must also agree to refrain from egg donation, storage, or banking during these same time periods.
⁃ \- Men with female partner of childbearing potential must: 1. Use a condom during sexual intercourse from screening and until 6 months after treatment. 2.
⁃ Ensure that their partner uses a highly effective method of contraception (as described above) 3. Agree to refrain from sperm donation, storage, or banking