Overview
The TIME-NL trial is a multicenter, randomized, open-label clinical trial in the Netherlands to assess the effect of the timing of the first administration of standard-of-care intravenous combination immunotherapy (early morning versus afternoon) in patients with metastatic melanoma. Patients will be randomized 1:1 to start standard-of-care ICI administration either before 10am (early morning arm; arm A) or after 1pm (afternoon arm; arm B). Patients will be stratified according to performance status and study center. The randomized clinical trial will be part of a hybrid design in which data from the randomized clinical trial will be combined with observational data.
Eligibility
Inclusion Criteria:
- Histologically or cytologically confirmed cutaneous melanoma, classified as irresectable (stage III) or metastatic (stage IV) disease.
- At least 18 years of age.
- World Health Organization (WHO) Performance Status 0-1.
- Measurable disease according to RECIST 1.1.
- Starting treatment with standard-of-care combination immunotherapy (ipilimumab+nivolumab) as first line treatment.
- Signed informed consent form
Exclusion Criteria:
- Uveal or mucosal melanoma (unknown primary melanoma is allowed).
- Use of systemic immunosuppressive medications. Inhaled or topical steroids are permitted.
- Use of adrenal replacement medications, e.g. hydrocortisone.
- Use of melatonin agonists.
- Prior systemic therapy for irresectable/metastatic melanoma (prior T-VEC is allowed)
- Prior systemic therapy for resectable melanoma in the last 6 months (neo-adjuvant and adjuvant treatment is allowed if at least 6 months ago).
- Use of investigational drugs.
