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NCT Number: NCT07696715

Timing of Immunotherapy in Melanoma

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.

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Key information

Conditions

Melanoma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Nerve Tissue Neuroectodermal Tumors Neuroendocrine Tumors Nevi and Melanomas Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Amsterdam UMC, Amsterdam, Netherlands

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Timing of first administration (early morning)

Other

The timing of the first administration of combination immunotherapy starting before 10am

Timing of immunotherapy (afternoon)

Other

The timing of the first administration of combination immunotherapy starting after 1pm

Primary outcomes

Best overall response rate

Time frame: from enrollment to 1year

Best overall response rate (radiological complete or partial response according to RECIST 1.1)

Study contacts

Contact information is provided by the study sponsor or research team.

Kalijn Bol, MD/PhD

CONTACT

[email protected]

+31243618800

Mirte Meijerink

CONTACT

[email protected]

Sponsors and collaborators

Lead sponsor

Radboud University Medical Center

Other

Registry information

Official study title

Timing of Immunotherapy in Melanoma (TIME-NL): Dancing to the Beat of the Circadian Rhythm

Acronym: TIME-NL

Important dates

Study start: 2026
Primary completion: 2029
Study completion: 2033
First posted: Jul 10, 2026
Registry last updated: Aug 12, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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