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

1 maggio 2026 aggiornato da: Swiss Cancer Institute

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

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.

Panoramica dello studio

Stato

Non ancora reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

The introduction of ICIs a decade ago revolutionized the treatment of various malignancies, particularly melanoma. Yet treatment responses are heterogenous and depend on patient characteristics such as sex and age, and tumor characteristics. The relationship between sex and ICI response in melanoma is complex and may be influenced by various factors, including the type of ICI, tumor mutation burden, presence of infiltrating immune cells, microbiome, and concomitant medications affect the immune system's ability to mount antitumor responses. While some retrospective data indicate poorer outcomes for female patients, in other real-world reports female sex is associated with better outcomes. Prospective, sex-stratified clinical studies are necessary to provide a definitive answer and to integrate sex as a critical variable in personalizing melanoma treatment strategies. Temporal variations in antibody responses and anticancer immunity after vaccination have been reported in both humans and mice. Circadian rhythms also remain an important regulator of immune cell activities. The optimal time for inducing adaptive immune responses consistently appears to be situated around or just before behavioral activity; for nocturnal mice this optimal window appears to be the afternoon, while in diurnal humans this may be the early morning. However, the optimal time of day for ICI administration is currently unknown. A retrospective single-center analysis of advanced melanoma patients showed that receiving less than 20% of the ICI infusions after 16h30 was associated with enhanced overall survival. In subgroup analyses, female patients had a significantly longer OS when less than 20% of the treatment was administered after 16h30.

Optimizing the timing of ICI therapy to target the immune system at the time of its highest sensitivity could significantly improve patient outcomes, particularly for female patients, without exposing patients to additional drugs and generating additional toxicity and costs. Given the limitations of retrospective analyses, a prospective randomized trial is essential to obtain results that could potentially change clinical practice.

Tipo di studio

Interventistico

Iscrizione (Stimato)

108

Fase

  • Fase 4

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Backup dei contatti dello studio

Luoghi di studio

  • Svizzera
      • Bellinzona, Svizzera, 6500
        • Ente Ospedaliero Cantonale (EOC)
        • Contatto:
        • Investigatore principale:
          • Cristina Mangas de Arriba, MD
      • Bern, Svizzera, 3010
        • Inselspital, Bern
        • Contatto:
        • Investigatore principale:
          • Berna Özdemir, MD
      • Geneva, Svizzera, 1211
        • Hôpitaux Universitaires de Genève HUG
      • Lausanne, Svizzera, 1011
        • Centre Hospitalier Universitaire Vaudois (CHUV)
        • Contatto:
        • Investigatore principale:
          • Sofiya MD Latifyan
      • Münsterlingen, Svizzera, 8596
        • Spital Thurgau (Kantonsspital Münserlingen und Frauenfeld)
        • Investigatore principale:
          • Ioannis Metaxas, MD
        • Contatto:
      • Sankt Gallen, Svizzera, 9007
        • HOCH Health Ostschweiz - Kantonsspital St. Gallen
        • Contatto:
        • Investigatore principale:
          • Tobias Peres, MD
      • Zurich, Svizzera, 8091
        • Universitätsspital Zürich USZ
    • Canton of Fribourg
      • Fribourg, Canton of Fribourg, Svizzera, 1708
        • Hfr Fribourg
        • Contatto:
        • Investigatore principale:
          • Bianca Gautron Moura, MD

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

  • Adulto
  • Adulto più anziano

Accetta volontari sani

No

Descrizione

Inclusion Criteria:

  • 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.
  • Women of childbearing potential must use effective contraception , not be pregnant or lactating and agree not to become pregnant during trial treatment and until 5 months after the last dose of trial treatment. A negative pregnancy test before inclusion into the trial is required for all women of childbearing potential.
  • 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.

Exclusion Criteria:

  • 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.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: ICI Infusions 8-12 h
Participants will be randomized 1:1 to receive standard-of-care ICI therapy in an early (08:00 - 12:00) infusion time window.
Droga: Immune Checkpoint Inhibitors

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)
Droga: Immune Checkpoint Inhibitors

Afternooon 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)
Comparatore attivo: ICI Infusions 15-18 h
Participants will be randomized 1:1 to receive standard-of-care ICI therapy in a late (15:00 - 18:00) infusion time window.
Droga: Immune Checkpoint Inhibitors

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)
Droga: Immune Checkpoint Inhibitors

Afternooon 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)

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Progression-free survival (PFS)
Lasso di tempo: From randomization to Progressive Desease or death, up to 6 years
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

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Overall survival (OS)
Lasso di tempo: From randomization to death, up to 6 year
OS is defined as the time from randomization until death due to any cause. Participants not experiencing an event will be censored at the last date they were known to be alive.
From randomization to death, up to 6 year
Objective response rate (ORR)
Lasso di tempo: At the end of trial treatment, up to 4 years from registration
Objective response rate (ORR) Objective response is defined as any complete response (CR) or partial response (PR) according to local assessment achieved during treatment. Any participant with CR or PR as best observed response during treatment will be considered as a success; otherwise, they will be considered as a failure. Participants without any tumor assessment, or with non-evaluable response (NE) during treatment, will be considered as failures for this endpoint.
At the end of trial treatment, up to 4 years from registration

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Swiss Cancer Institute

Investigatori

  • Cattedra di studio: Berna Özdemir, MD et phil., Insel Gruppe AG, University Hospital Bern

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Stimato)

1 settembre 2026

Completamento primario (Stimato)

1 giugno 2030

Completamento dello studio (Stimato)

1 giugno 2032

Date di iscrizione allo studio

Primo inviato

1 maggio 2026

Primo inviato che soddisfa i criteri di controllo qualità

1 maggio 2026

Primo Inserito (Effettivo)

7 maggio 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

7 maggio 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

1 maggio 2026

Ultimo verificato

1 maggio 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • SCI-004_MELCHRONO

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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