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.
調査の概要
詳細な説明
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.
研究の種類
入学 (推定)
段階
- フェーズ2
連絡先と場所
研究連絡先
- 名前：Christina Müller, PhD
- 電話番号：+41 31 389 91 91
- メール：trials@swisscancerinstitute.ch
研究連絡先のバックアップ
- 名前：Lenka Vokalova, PhD
- 電話番号：+41 31 389 91 91
- メール：trials@swisscancerinstitute.ch
研究場所
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Bellinzona、スイス、6500
- Ente Ospedaliero cantonale (EOC)
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コンタクト：
- Cristina Mangas de Arriba, MD
- 電話番号：+41 91 811 94 11
- メール：cristina.mangas@eoc.ch
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主任研究者：
- Cristina Mangas de Arriba, MD
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Bern、スイス、3010
- Inselspital, Bern
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主任研究者：
- Berna Özdemir, MD
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コンタクト：
- Berna Oezdemir, MD PhD
- 電話番号：+41 31 632 81 95
- メール：berna.oezdemir@insel.ch
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Geneva、スイス、1211
- Hôpitaux Universitaires de Genève HUG
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Lausanne、スイス、1011
- Centre Hospitalier Universitaire Vaudois (CHUV)
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コンタクト：
- Sofiya Latifyan, MD
- 電話番号：+41 21 314 11 11
- メール：sofiya.latifyan@chuv.ch
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主任研究者：
- Sofiya MD Latifyan
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Münsterlingen、スイス、8596
- Spital Thurgau (Kantonsspital Münserlingen und Frauenfeld)
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主任研究者：
- Ioannis Metaxas, MD
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コンタクト：
- Ioannis Metaxas, MD
- 電話番号：+41 58 144 78 50
- メール：ioannis.metaxas@stgag.ch
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Sankt Gallen、スイス、9007
- HOCH Health Ostschweiz - Kantonsspital St. Gallen
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コンタクト：
- Tobias Peres, MD
- 電話番号：+41 71 494 38 78
- メール：tobias.peres@h-och.ch
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主任研究者：
- Tobias Peres, MD
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Zurich、スイス、8091
- Universitätsspital Zürich USZ
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Canton of Fribourg
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Fribourg、Canton of Fribourg、スイス、1708
- Hfr Fribourg
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コンタクト：
- Bianca Gautron Moura, MD
- 電話番号：+41 26 306 22 60
- メール：Bianca.gautronmoura@h-fr.ch
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主任研究者：
- Bianca Gautron Moura, MD
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参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：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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アクティブコンパレータ：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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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Progression-free survival (PFS)
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Overall survival (OS)
時間枠：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)
時間枠：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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協力者と研究者
スポンサー
捜査官
- スタディチェア：Berna Özdemir, MD PhD、Insel Gruppe AG, University Hospital Bern
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- SCI-004_MELCHRONO
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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