DONIMI


Protocolnummer:
M19DON - DONIMI

Ziekenhuizen:
NKI / A.v.L ziekenhuis Amsterdam

Titel:

Dit is een open-label fase Ib studie, waarin 45 stadium III melanoompatiënten met RECIST 1.1 meetbare nieuwe of terugkerende ziekte worden geïncludeerd. IFN-gamma signatuur hoge patiënten zullen worden gerandomiseerd tussen 6 weken behandeling met:

  • - nivolumab 240 mg q3wk (10 patiënten) of;
  • - domatinostat 200mg BID d1-14 + nivolumab 240 mgq3wk (10 patiënten).
    IFN-gamma signatuur lage patiënten zullen worden gerandomiseerd tussen 6 weken behandeling met:
  • - domatinostat 200mg BID d1-14 + nivolumab 240 mgq3wk (10 patiënten) of;
  • - domatinostat 200mg OD/BID d1-14 + nivolumab 240 mgq3wk + ipilimumab 80 mg q3wk (15 patiënten).
    Bij randomisatie wordt er gestratificeerd op behandelend centrum.
    Na de operatie zullen de patiënten in week 12 starten met adjuvant nivolumab 480 mg elke 4 weken, voor 52 weken. Hierna volgt 2 jaar follow-up, volgens de standaardbehandeling per instituut.


Behandeling:
met nivolumab +/- domatinostat +/- ipilimumab.

Stadium:
Stadium III

Belangrijkste in/exclusiecriteria:

Inclusion criteria

• Adults at least 18 years of age.
• World Health Organization (WHO) Performance Status 0 or 1.
• Cytologically or histologically confirmed resectable stage III cutaneous melanoma (unknown primary also allowed) with one or more macroscopic lymph node metastases (measurable according to RECIST 1.1), that can be biopsied, and no history of in-transit metastases within the last 6 months.
• No other malignancies, except adequately treated and a cancer-related life-expectancy of more than 5 years.
• No immunosuppressive medications within 6 months prior trial registration.
• Screening laboratory values must meet the following criteria: WBC ≥ 2.0x109/L, Neutrophils ≥1.5x109/L, Platelets ≥100 x109/L, Hemoglobin ≥5.5 mmol/L, Creatinine ≤1.5x ULN, AST ≤ 1.5 x ULN, ALT ≤ 1.5 x ULN, Bilirubin ≤1.5 X ULN.
• Normal LDH.

Exclusion criteria

• Distantly metastasized melanoma
• Uveal or mucosal melanoma.• History of in-transit metastases within the last 6 months.
• History of in-transit metastases within the last 6 months.
• Prior CTLA-4 or PD-1/PD-L1 targeting immunotherapy.
• Prior targeted therapy targeting BRAF and/or MEK.
• Prior radiotherapy.
• Patients will be excluded if they test positive for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody), indicating acute or chronic infection; if treated and being at least one year free from HCV patients are allowed to participate.
• Patients will be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
• Patients with a marked baseline prolongation of QT/QTc interval, e.g., repeated demonstration of a QTc interval >450 msec (Grade 1 NCI-CTCAE); Long-QT-Syndrome) and patients receiving agents known to prolong the QT interval and known risk of Torsades de Pointes.
• Patients with significant current cardiovascular disease including: − Unstable angina pectoris within 6 months prior to screening

Contactpersoon:
Prof. dr. C. U. Blank, AVL Amsterdam

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