NKI / A.v.L ziekenhuis Amsterdam
Dit is een open-label gerandomiseerde fase II studie naar het effect van adjuvante nivolumab versus observatie (geen placebo!) bij volledig chirurgisch verwijderde Merkel Cel Carcinoom (MCC) patienten .
Stadium II / III
Behandeling: - Nivolumab 480 mg / 4 weken tot maximaal 13 doses (2/3 patienten) - Observatie (geen placebo!) in 1/3 van patienten
1. The patient is willing and able to give written informed consent. 2. Central histological confirmation of diagnosis of Merkel cell carcinoma (MCC). 3. All MCC manifestations have been completely resected by surgery within 12 weeks before enrolment. 4. No currently present metastases (as confirmed by standard imaging studies (e.g. suggested by S2k guidelines). 5. No previous systemic therapy for MCC. 6. Required values for initial laboratory tests: · WBC ≥ 2000/uL · ANC ≥ 1000/uL · Platelets ≥ 75 x 103 /uL ·Hemoglobin ≥ 8 g/dL (≥ 80 g/L) · Creatinine ≤ 2.0 x ULN · AST/ALT ≤ 2.5 x ULN ·Total Bilirubin ≤ 2.0 x ULN (except patients with Gilbert’s Syndrome, who must have a total bilirubin less than 3.0 mg/dL) 7. ECOG performance status of 0 or 1. 8. No active or chronic infection with HIV, Hepatitis B or C. 9. Men and women, ≥ 18 years of age. 10. Women of childbearing potential (WOCBP) must be using an adequate method of contraception (Pearl-Index < 1) to avoid pregnancy during treatment phase and for additional 5 months after the last dose of nivolumab, in such a manner that the risk of pregnancy is minimized. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not post-menopausal. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours before the start of nivolumab. 11. Men of fathering potential must be using an adequate method of contraception to avoid conception during treatment phase and for additional 7 months after the last dose of nivolumab) in such a manner that the risk of pregnancy is minimized.
1. Autoimmune disease: Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn’s Disease, are excluded from this study, as are patients with a history of symptomatic disease requiring systemic steroids (e.g., rheumatoid arthritis, systemic progressive sclerosis, systemic lupus erythematosus, autoimmune vasculitis); autoimmune motor neuropathy. 2. Other serious illnesses, e.g., serious infections requiring i.v. antibiotics. 3. The patient is known to be positive for Human Immunodeficiency Virus (HIV) or other chronic infections (HBV, HCV) or has another confirmed or suspected immunosuppressive or immune deficient condition. 4. Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of nivolumab hazardous or obscure the interpretation of AEs, such as a condition associated with frequent diarrhea. 5. Any non-oncology vaccine therapy for up to 1 month before or after any dose of nivolumab. 6. A history of prior or current treatment with a T cell potentiating agent (e.g. IL-2, interferon, anti-CTLA-4, anti-CD137, anti-PD1, anti-PD-L1, or anti-OX40 antibody). 7. Chronic use of immunosuppressive agents or systemic corticosteroids. 8. Women of childbearing potential (WOCBP), defined above in Section 5.1, who: · are unwilling or unable to use an acceptable method of contraception to avoid pregnancy during treatment phase and for additional 5 months after the last dose of investigational product · have a positive pregnancy test at baseline · are pregnant or breastfeeding. 9. The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent or to comply with the trial procedures. 10. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness. 11. Men of reproductive potential unwilling to use an adequate method to avoid pregnancy during treatment phase and for additional 7 months after the last dose of investigational product. 12. Use of any investigational or non-registered product (drug or vaccine) other than the study treatment.
dr. M.E.T. Tesselaar, AVL Amsterdam
dr. A.C.J. van Akkooi, AVL Amsterdam