Timing of Immunotherapy in Melanoma

NCT07696715 | Not Yet Recruiting

• 2 other identifiers: R0128980NL-011107
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Melanoma

Keywords

melanoma; chronoimmunotherapy; timing

Outcome Measures

Primary Outcomes (1)

• Best overall response rate

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

  from enrollment to 1year

Study Arms (2)

A: early morning immunotherapy

ACTIVE COMPARATOR

Standard-of-care immune checkpoint inhibition with ipilimumab + nivolumab with the first administration starting before 10am

Other: Timing of first administration (early morning)

B: afternoon immunotherapy

ACTIVE COMPARATOR

Standard-of-care immune checkpoint inhibition with ipilimumab + nivolumab with the first administration starting after 1pm

Other: Timing of immunotherapy (afternoon)

Interventions

Timing of first administration (early morning) OTHER

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

A: early morning immunotherapy

Timing of immunotherapy (afternoon) OTHER

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

B: afternoon immunotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (4)

Amsterdam UMC

Amsterdam, Netherlands

Location

Antoni van Leeuwenhoek

Amsterdam, Netherlands

Location

Leiden UMC

Leiden, Netherlands

Location

ErasmusMC

Rotterdam, Netherlands

Location

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Kalijn Bol, MD/PhD

CONTACT

+31243618800; kalijn.bol@radboudumc.nl

Mirte Meijerink

CONTACT

studies.onco@radboudumc.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2026
• First Posted: July 10, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): September 30, 2029
• Study Completion (Estimated): September 30, 2033
• Last Updated: July 22, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

NL (4)