MELCHRONO: A Prospective Randomized Study Investigating Chrono-immunotherapy for Advanced Melanoma.
MELCHRONO: A Prospective Randomized Study Investigating Chrono-immunotherapy for Advanced Melanoma. A Phase II Trial.
연구 개요
상태
상세 설명
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.
연구 유형
등록 (추정된)
단계
- 2 단계
연락처 및 위치
연구 연락처
- 이름: Christina Müller, PhD
- 전화번호: +41 31 389 91 91
- 이메일: trials@swisscancerinstitute.ch
연구 연락처 백업
- 이름: Lenka Vokalova, PhD
- 전화번호: +41 31 389 91 91
- 이메일: trials@swisscancerinstitute.ch
연구 장소
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Bellinzona, 스위스, 6500
- Ente Ospedaliero cantonale (EOC)
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연락하다:
- Cristina Mangas de Arriba, MD
- 전화번호: +41 91 811 94 11
- 이메일: cristina.mangas@eoc.ch
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수석 연구원:
- Cristina Mangas de Arriba, MD
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Bern, 스위스, 3010
- Inselspital, Bern
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수석 연구원:
- Berna Özdemir, MD
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연락하다:
- Berna Oezdemir, MD PhD
- 전화번호: +41 31 632 81 95
- 이메일: berna.oezdemir@insel.ch
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Geneva, 스위스, 1211
- Hôpitaux Universitaires de Genève HUG
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Lausanne, 스위스, 1011
- Centre Hospitalier Universitaire Vaudois (CHUV)
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연락하다:
- Sofiya Latifyan, MD
- 전화번호: +41 21 314 11 11
- 이메일: sofiya.latifyan@chuv.ch
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수석 연구원:
- Sofiya MD Latifyan
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Münsterlingen, 스위스, 8596
- Spital Thurgau (Kantonsspital Münserlingen und Frauenfeld)
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수석 연구원:
- Ioannis Metaxas, MD
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연락하다:
- Ioannis Metaxas, MD
- 전화번호: +41 58 144 78 50
- 이메일: ioannis.metaxas@stgag.ch
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Sankt Gallen, 스위스, 9007
- HOCH Health Ostschweiz - Kantonsspital St. Gallen
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연락하다:
- Tobias Peres, MD
- 전화번호: +41 71 494 38 78
- 이메일: tobias.peres@h-och.ch
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수석 연구원:
- Tobias Peres, MD
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Zurich, 스위스, 8091
- Universitätsspital Zürich USZ
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Canton of Fribourg
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Fribourg, Canton of Fribourg, 스위스, 1708
- Hfr Fribourg
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연락하다:
- Bianca Gautron Moura, MD
- 전화번호: +41 26 306 22 60
- 이메일: Bianca.gautronmoura@h-fr.ch
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수석 연구원:
- Bianca Gautron Moura, MD
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참여기준
자격 기준
공부할 수 있는 나이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
설명
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.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
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실험적: 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.
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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
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
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활성 비교기: 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.
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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
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
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Progression-free survival (PFS)
기간: From randomization to Progressive Desease or death, up to 6 years
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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.
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From randomization to Progressive Desease or death, up to 6 years
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Overall survival (OS)
기간: From randomization to death, up to 6 year
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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.
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From randomization to death, up to 6 year
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Objective response rate (ORR)
기간: At the end of trial treatment, up to 4 years from registration
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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.
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At the end of trial treatment, up to 4 years from registration
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공동 작업자 및 조사자
수사관
- 연구 의자: Berna Özdemir, MD PhD, Insel Gruppe AG, University Hospital Bern
연구 기록 날짜
연구 주요 날짜
연구 시작 (추정된)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
키워드
추가 관련 MeSH 약관
기타 연구 ID 번호
- SCI-004_MELCHRONO
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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