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

ConditionsMelanomaAdvanced Melanoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorSwiss Cancer Institute

About this 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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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)

  • Immune Checkpoint Inhibitors

    Drug

    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)

Treatment groups

108 Participants
are divided into 2 treatment groups
Group A: ICI Infusions 8-12 hExperimental treatment 1 intervention
Group B: ICI Infusions 15-18 hActive comparator 1 intervention

Trial outcomes

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.

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

Secondary outcomes

1

Overall survival (OS)

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.

Time frame
From randomization to death, up to 6 year
2

Objective response rate (ORR)

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.

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

Other outcomes

Sponsors and contacts

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Swiss Cancer Institute

Lead sponsor

Source ClinicalTrials.gov
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