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

30 lipca 2026 zaktualizowane przez: Swiss Cancer Institute

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

Przegląd badań

Status

Jeszcze nie rekrutacja

Warunki

Interwencja / Leczenie

Szczegółowy opis

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.

Typ studiów

Interwencyjne

Zapisy (Szacowany)

108

Faza

  • Faza 2

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Kontakt w sprawie studiów

Kopia zapasowa kontaktu do badania

Lokalizacje studiów

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

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

  • Dorosły
  • Starszy dorosły

Akceptuje zdrowych ochotników

Nie

Opis

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.

Plan studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Leczenie
  • Przydział: Randomizowane
  • Model interwencyjny: Przydział równoległy
  • Maskowanie: Brak (otwarta etykieta)

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Eksperymentalny: 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.
Lek: 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)
Lek: 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)
Aktywny komparator: 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.
Lek: 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)
Lek: 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)

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Opis środka
Ramy czasowe
Progression-free survival (PFS)
Ramy czasowe: 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

Miary wyników drugorzędnych

Miara wyniku
Opis środka
Ramy czasowe
Overall survival (OS)
Ramy czasowe: 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)
Ramy czasowe: 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

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

Swiss Cancer Institute

Śledczy

  • Krzesło do nauki: Berna Özdemir, MD PhD, Insel Gruppe AG, University Hospital Bern

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów (Szacowany)

1 września 2026

Zakończenie podstawowe (Szacowany)

1 czerwca 2030

Ukończenie studiów (Szacowany)

1 czerwca 2032

Daty rejestracji na studia

Pierwszy przesłany

1 maja 2026

Pierwszy przesłany, który spełnia kryteria kontroli jakości

1 maja 2026

Pierwszy wysłany (Rzeczywisty)

7 maja 2026

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Rzeczywisty)

31 lipca 2026

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

30 lipca 2026

Ostatnia weryfikacja

1 lipca 2026

Więcej informacji

Terminy związane z tym badaniem

Słowa kluczowe

Dodatkowe istotne warunki MeSH

Inne numery identyfikacyjne badania

  • SCI-004_MELCHRONO

Informacje o lekach i urządzeniach, dokumenty badawcze

Bada produkt leczniczy regulowany przez amerykańską FDA

Nie

Bada produkt urządzenia regulowany przez amerykańską FDA

Nie

Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .

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