MELCHRONO: A Prospective Randomized Study Investigating Chrono-immunotherapy for Advanced Melanoma.

NCT07574047 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: SCI-004_MELCHRONO
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 8

Brief Summary

Melanoma remains a common cancer with rising incidence, and despite significant improvements with immune checkpoint inhibitors (ICIs), clinical outcomes remain heterogeneous. Retrospective analyses across multiple tumor types, including melanoma, suggest that earlier daytime administration of ICIs may enhance therapeutic effectiveness, potentially due to circadian modulation of immune function. A pronounced survival benefit has been observed particularly among female patients receiving earlier infusions. This trial prospectively evaluates whether aligning ICI administration with circadian immune activity can improve outcomes in melanoma and support the development of sex-specific optimization of immunotherapy.

Conditions

Melanoma; Advanced Melanoma

Keywords

Advanced melanoma; chrono-immunotherapy; phase IV; Nivolumab; Ipilimumab; relatlimab; Pembrplizumab; Opdivo; Keytruda; Opdualag; Yervoy; immune checkpoint inhibitor

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  Progression-free survival (PFS), defined as time from randomization to progression according to local assessment or death. Participants not experiencing an event will be censored at the date of the last available assessment before initiation of a new anti-cancer treatment, if any.

  From randomization to Progressive Desease or death, up to 6 years

Secondary Outcomes (2)

• Overall survival (OS)

  From randomization to death, up to 6 year

• Objective response rate (ORR)

  At the end of trial treatment, up to 4 years from registration

Study Arms (2)

ICI Infusions 8-12 h

EXPERIMENTAL

Participants will be randomized 1:1 to receive standard-of-care ICI therapy in an early (08:00 - 12:00) infusion time window.

Drug: Immune Checkpoint Inhibitors

ICI Infusions 15-18 h

ACTIVE COMPARATOR

Participants will be randomized 1:1 to receive standard-of-care ICI therapy in a late (15:00 - 18:00) infusion time window.

Drug: Immune Checkpoint Inhibitors

Interventions

Immune Checkpoint Inhibitors DRUG

Morning administration of ICI per physician's choice, according to local practice: Nivolumab (Opdivo®) Monotherapy - 240 mg administered intravenously every 2 weeks (Q2W) Pembrolizumab (Keytruda®) Monotherapy \- 200 mg administered intravenously every 3 weeks (Q3W) Ipilimumab (Yervoy®) + Nivolumab (Opdivo®) Combination Therapy * Induction Phase: * Ipilimumab 3 mg/kg intravenously every 3 weeks (Q3W) * Nivolumab 1 mg/kg intravenously every 3 weeks (Q3W) * Administered for 4 cycles * Maintenance Phase: * Nivolumab 240 mg administered intravenously every 2 weeks (Q2W) Nivolumab + Relatlimab Fixed-Dose Combination (Opdualag®) Nivolumab 480 mg and relatlimab 160 mg administered intravenously every 4 weeks (Q4W)

ICI Infusions 8-12 h

Eligibility Criteria

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

You may qualify if:

• Written informed consent according to Swiss law and ICH GCP E6 regulations before registration and prior to any trial specific procedures.
• Histologically confirmed unresectable cutaneous stage III or stage IV melanoma. Note: Participants with central nervous system (CNS) metastases are eligible.
• Participants with a previously treated other malignancy are eligible, if the risk of the prior malignancy interfering with either safety or efficacy endpoints is very low.
• Measurable or evaluable disease.
• Age ≥ 18 years.
• Patients deemed suitable for ICI therapy based on the local investigator's clinical assessment.
• ECOG performance status 0-2.
• Men agree not to donate sperm or to father a child during trial treatment and until 5 months after the last dose of trial treatment.

You may not qualify if:

• Prior treatment with any systemic anti-cancer therapy; with the exception of prior adjuvant anti-PD-1 or BRAF/MEK inhibitor therapy if the time from last dose to recurrence is more than 6 months.
• Recent treatment (within 28 days prior to first dose) with any experimental drug.
• Known history of allogeneic organ transplant.
• Uveal or mucosal melanoma.
• Receipt of live attenuated vaccine within 28 days prior to first dose.
• Any concomitant drugs contraindicated for use with the trial drugs according to the approved product information.
• Known hypersensitivity to trial drug(s) or to any component of the trial drug(s).
• Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment and follow-up, affect participant compliance or place the participant at high risk from treatment-related complications.

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (8)

HFR Fribourg

Fribourg, Canton of Fribourg, 1708, Switzerland

Location

Ente Ospedaliero Cantonale (EOC)

Bellinzona, 6500, Switzerland

Location

Inselspital, Bern

Bern, 3010, Switzerland

Location

Hôpitaux Universitaires de Genève HUG

Geneva, 1211, Switzerland

Location

Centre Hospitalier Universitaire Vaudois (CHUV)

Lausanne, 1011, Switzerland

Location

Spital Thurgau (Kantonsspital Münserlingen und Frauenfeld)

Münsterlingen, 8596, Switzerland

Location

HOCH Health Ostschweiz - Kantonsspital St. Gallen

Sankt Gallen, 9007, Switzerland

Location

Universitätsspital Zürich USZ

Zurich, 8091, Switzerland

Location

MeSH Terms

Conditions

Melanoma

Interventions

Immune Checkpoint Inhibitors

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

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Officials

• Berna Özdemir, MD et phil.

  Insel Gruppe AG, University Hospital Bern

  STUDY CHAIR

Central Study Contacts

Lenka Vokalova, PhD

CONTACT

+41 31 389 91 91; trials@swisscancerinstitute.ch

Christina Müller, PhD

CONTACT

+41 31 389 91 91; trials@swisscancerinstitute.ch

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, randomized, multicenter, open-label phase IV trial. Participants will be randomized 1:1 to receive standard-of-care ICI therapy in either an early (08:00 - 12:00) or late (15:00 - 18:00) infusion time window. Participants will be randomized in a 1:1 ratio for a total of 54 per time window using the minimization method 31 with 80% allocation probability according to the stratification factors: * Treatment: Ipilimumab and Nivolumab versus Nivolumab and Relatlimab versus anti-PD1 mono (assumed ratio 50 :30 :20) * Sex: female versus male

Study Record Dates

• First Submitted: May 1, 2026
• First Posted: May 7, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): June 1, 2032
• Last Updated: May 7, 2026

Record last verified: 2026-05

Locations

CH (8)