Timing of Immunotherapy in Melanoma (TIME-NL) trial

Timing of Immunotherapy in Melanoma (TIME-NL): dancing to the beat of the circadian rhythm - TIME trial

Status

Active, not recruiting

Phases

Unknown

Study type

Interventional

Source

NL-OMON

Registry ID

NL-OMON61286

Enrollment

170

Registered

2025-11-24

Start date

2026-07-01

Completion date

Unknown

Last updated

2026-06-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

melanoma skin cancer

Interventions

In the TIME-NL trial, patients will be randomized to starting their first ICI administration of ipilimumab+nivolumab either before 10am (early morning arm) or after 1pm (afternoon arm).

Eligibility

Age

18 Years to 99 Years

Inclusion criteria

Inclusion criteria: Histologically or cytologically confirmed cutaneous melanoma, classified as irresectable (stage III) or metastatic (stage IV) disease.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.

Exclusion criteria

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 (adjuvant treatment is allowed if at least 6 months ago).Use of investigational drugs.

Design outcomes

Primary

Measure	Time frame
The primary study endpoint of the TIME-NL trial is to determine the best overall response rate (radiological response according to RECIST 1.1) to combined immunotherapy administration in the early morning versus the afternoon.	—

Secondary

Measure	Time frame
The primary study endpoint of the TIME-NL trial is to determine the best overall response rate (radiological response according to RECIST 1.1) to combined immunotherapy administration in the early morning versus the afternoon. Secondary endpoints are progression-free survival, overall survival and toxicity. Exploratory endpoints include broad (immunological) analyses to enhance our understanding of pharmacokinetics and immune-pharmacodynamics in regards to the circadian rhythm.	—

Measure

Time frame

The primary study endpoint of the TIME-NL trial is to determine the best overall response rate (radiological response according to RECIST 1.1) to combined immunotherapy administration in the early morning versus the afternoon. Secondary endpoints are progression-free survival, overall survival and toxicity. Exploratory endpoints include broad (immunological) analyses to enhance our understanding of pharmacokinetics and immune-pharmacodynamics in regards to the circadian rhythm.

—

Countries

Netherlands

Contacts

Public ContactK.F. Bol

Radboud Universitair Medisch Centrum

Kalijn.Bol@radboudumc.nl0243618800

Outcome results

None listed

Source: NL-OMON (via WHO ICTRP) · Data processed: Jul 3, 2026