腫瘍に対して行われた生物学的検査に基づいて再発リスクが高いと疑われる限局性子宮平滑筋腫患者における術後化学療法への関心 (L-UteCIN)
CINSARC 高リスク局所切除子宮平滑筋腫 - 肉腫 15 患者における補助化学療法への関心
Addition of postoperative chemotherapy to prevent or delay recurrence in patients newly diagnosed with localized uterine leiomyosarcoma and who have undergone complete tumor surgery.
調査の概要
詳細な説明
This is a biological driven study comprising:
- a multicenter, randomized and comparative phase II trial designed to demonstrate whether adding 4 cycles of post-operative chemotherapy improves relapse-free survival as compared with follow-up (standard management) in patients with resected FIGO stage I uterine leiomyosarcoma, considered at high-risk according to CINSARC NanoCind® signature.
- a prospective cohort for patients with resected FIGO stage I uterine leiomyosarcoma, considered at low-risk according to CINSARC NanoCind® signature.
HIGH-RISK (HR) CINSARC patients will be randomized post-operatively between the two arms of treatment, i.e. standard treatment (active post-surgical surveillance) or chemotherapy, with a 1:1 randomization on one factor: morcellation versus no morcellation of uterine tumor.
LOW-RISK (LR) CINSARC patients' data will be prospectively collected
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：Amel MEKALICHE, MS
- 電話番号：+33 761947045
- メール：a-mekaliche@unicancer.fr
研究場所
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Angers、フランス、49100
- まだ募集していません
- Institut de Cancerologie de L'Ouest (Ico)
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主任研究者：
- Patrick SOULIÉ, MD
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Besançon、フランス、25030
- まだ募集していません
- Hopital Jean Minjoz
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主任研究者：
- Loic CHAIGNEAU, MD
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Bordeaux、フランス、33076
- まだ募集していません
- Institut Bergonie
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主任研究者：
- Maud TOULMONDE, MD
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Caen、フランス、14176
- まだ募集していません
- Centre Francois Baclesse
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主任研究者：
- Zoé NEVIERE, MD
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Clermont-Ferrand、フランス、63011
- まだ募集していません
- Centre Jean Perrin
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主任研究者：
- Pascale DUBRAY-LONGERAS, MD
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Dijon、フランス、21079
- まだ募集していません
- Centre Georges Francois Leclerc
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主任研究者：
- Isabelle DESMOULINS, MD
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Limoges、フランス、87042
- まだ募集していません
- Chu Limoges
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主任研究者：
- Tiffany DARBAS, MD
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Lyon、フランス、69373
- まだ募集していません
- Centre Léon Berard
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主任研究者：
- Isabelle RAY-COCUARD, MD PhD
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Marseille、フランス、13273
- まだ募集していません
- Institut Paoli Calmettes
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主任研究者：
- François BERTUCCI, MD PhD
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Marseille、フランス、13385
- 募集
- La Timone University Hospital
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主任研究者：
- Florence DUFFAUD, MD PhD
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Nice、フランス、06189
- まだ募集していません
- Centre Antoine Lacassagne
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主任研究者：
- Agnès DUCOULOMBIER, MD
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Paris、フランス、75014
- まだ募集していません
- Hôpital Cochin
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主任研究者：
- Sixtine DE PERCIN, MD
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Paris、フランス
- まだ募集していません
- Institut Curie
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主任研究者：
- Clément BONET, MD
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Paris、フランス、75010
- まだ募集していません
- Hopital Saint Louis
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主任研究者：
- Tiphaine LAMBERT, MD
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Paris、フランス、75020
- まだ募集していません
- Groupe Hospitalier Diaconesses Croix St Simon
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主任研究者：
- Frédéric SELLE, MD
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Paris、フランス、75020
- まだ募集していません
- Hopital Tenon
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主任研究者：
- Laurent SEKNAZI, MD
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Poitiers、フランス、86000
- まだ募集していません
- Chu de Poitiers
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主任研究者：
- Nicolas ISAMBERT, MD PHD
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Rennes、フランス、35042
- まだ募集していません
- Centre Eugene Marquis
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主任研究者：
- Christophe PERRIN, MD
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Rouen、フランス、76038
- まだ募集していません
- Centre Henri Becquerel
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主任研究者：
- Cécile GUILLEMET, MD
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Saint-Herblain、フランス、44805
- まだ募集していません
- Institut de cancerologie de l'ouest site Rene Gauducheau
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主任研究者：
- Pierre KUBICEK, MD
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Strasbourg、フランス
- まだ募集していません
- Institut de Cancerologie Strasbourg Europe (Icans)
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コンタクト：
- Jean-Emmanuel KURTZ, MD
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Toulouse、フランス、31052
- まだ募集していません
- Institut Claudius Regaud
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主任研究者：
- Thibaud VALENTIN, MD
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Tours、フランス、37000
- まだ募集していません
- CHU Bretonneau
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主任研究者：
- Mathilde CANCEL, MD
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Vandœuvre-lès-Nancy、フランス、54519
- まだ募集していません
- Centre Alexis Vautrin
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主任研究者：
- Maria RIOS, MD
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Villejuif、フランス、94800
- 募集
- Gustave Roussy
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主任研究者：
- Patricia PAUTIER, MD
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
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Patient must have a histologically confirmed diagnosis of uterine leiomyosarcoma obtained less than 8 weeks from the surgery
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Eastern cooperative oncology group (ECOG) performance status (PS) 0 or 1
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Patient was previously untreated with chemotherapy for a sarcoma, and did not receive anthracyclines and/or trabectedin for another cancer
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Available Formalin Fixed Paraffin Embedded (FFPE) tumor blocks in sufficient quantity and quality to allow CINSARC NanoCind® qualification (low-risk or high-risk)
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Age ≥ 18 years and ≤ 75 years
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FIGO 2018 classification stage I (IA and IB), with complete resection (total hysterectomy and optional bilateral oophorectomy; possible ovarian preservation is feasible in selected cases)
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No measurable disease, as assessed by the investigator: normal post-operative thoracic, abdominal and pelvic CT-scan or normal MRI of abdomen and pelvis + normal chest CT performed within 4 weeks prior to inclusion or randomization in the study
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Signed informed consent form prior to any trial specific procedures consistent with international conference on harmonisation - good clinical practice (ICH-GCP) and local legislation
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Patient must be affiliated to a social security system or in possession of equivalent private health insurance (according to local regulations for participation in clinical trials).
Additional inclusion criteria for randomization
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Inclusion criteria checked at study entry are all still met at the time of randomization
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High-risk CINSARC signature
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Patient must have a diagnosis of uterine leiomyosarcoma confirmed by a local sarcoma expert pathologist from RRePS (Sarcoma Pathology Reference Network from NETSARC +) locally or by the study central RRePS expert pathologist.
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Adequate hematologic organ function:
- absolute neutrophil count ≥ 1.5 Giga/ L
- hemoglobin ≥ 9 g/dL
- platelets ≥ 100 Giga/L
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Adequate renal function: serum creatinine ≤ 1.5 mg/dL (≤ 132.6 µmol/L) or calculated creatinine clearance ≥60 mL/min (by the Cockcroft and Gault formula)
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Adequate liver function: total bilirubin ≤ upper limit of normal (ULN), transaminases ≤ 2.5 x ULN, alkaline phosphatases ≤ 1.5 x ULN
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Adequate cardiac function: cardiac ultrasound and/or isotopic ventriculography, shortening fraction (SF) > 30%, Left Ventricular Ejection Fraction (LVEF) (per ultrasound or scintigraphy) > 50%
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Creatine phosphokinase (CPK) ≤ 2,5 x ULN
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Albumin ≥ 25 g/L
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Signed informed consent form for the randomized phase, consistent with ICH-GCP and local legislation.
Exclusion Criteria:
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Exclusion criteria:
- All other histology types of uterine sarcoma (adenosarcoma, endometrial sarcoma, undifferentiated uterine sarcoma)
- Prior or concurrent malignant disease diagnosed or treated in the last 5 years except for adequately treated in situ carcinoma of the cervix, basal or squamous skin cell carcinoma, or in situ transitional bladder cell carcinoma
- Planned pelvic post-operative radiation therapy
- Metastatic or measurable disease on CT-Scan
- Known hypersensitivity to doxorubicin or trabectedin or to any of the excipients
- Any contra-indication for the use of doxorubicin and/or trabectedin treatment
- Participation in another therapeutic trial within the 30 days prior to inclusion in the study
- Active viral hepatitis B or C or known human immunodeficiency virus (HIV) infection.
- Prior anticancer therapy, including radiotherapy, endocrine therapy, immunotherapy, chemotherapy (CT) or other investigational agents within the last 4 weeks (6 weeks for nitrosoureas and mitomycin C)
- Cardiovascular dysfunction:
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Congestive heart failure (New York Heart Association [NYHA]) ≥ 2)
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Myocardial infarction <6 months before study
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Poorly controlled cardiac arrhythmias
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Uncontrolled hypertension
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Unstable (angina symptoms at rest) or new-onset angina (begun within the last 3 months) 11. Ongoing infection > Grade 2 according to NCI-CTCAE v5.0 12. Breastfeeding woman 13. Patients unwilling or unable to comply with the medical procedures and follow-up required by the trial because of geographic, familial, social, or psychological reasons 14. Persons deprived of their liberty or under protective custody or guardianship.
Additional exclusion criteria for randomization 15. At least one of the exclusion criteria check at study entry is met at the time of randomization 16. Unknown risk for CINSARC signature 17. For patients who require a pathological review by the study central pathologist, failure to obtain a confirmed diagnosis at randomization 18. More than 13 weeks have elapsed since the surgery procedure. 19. Patient receiving phenytoin within 88 hours prior to randomisation and or live attenuated vaccines within 14 days prior to randomisation and or CYP3A4 inhibitors (e.g. oral ketoconazole, fluconazole, ritonavir, clarithromycin or aprepitant) and or strong CYP3A4 inducers (e.g. rifampicin, phenobarbital, St John's wort).
Criteria for continuing in the prospective cohort :
- Patient must have a diagnosis of uterine leiomyosarcoma confirmed by a sarcoma expert pathologist or by the study central pathologist
- Patients with a low-risk CINSARC signature
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：防止
- 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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介入なし：Arm A
Standard of care : Active surveillance |
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|
実験的：Arm B
Experimental treatment: 4 cycle of Doxorubicine + trabectedin |
60 mg/m² intravenous (IV) at Day 1 every 3 weeks (4 cycles) 1.1 mg/m² intravenous (IV) at Day 1 every 3 weeks (4 cycles)
他の名前：
|
|
介入なし：Prospective Cohort
Standard of care : Active surveillance |
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 |
|---|---|---|
|
Relapse-free survival
時間枠：From randomization or enrollment to disease recurrence or death, up to 5 years
|
The relapse-free survival is defined as the time from the date of randomization assignment (or the date of enrollment for patients in the prospective cohort) to the date of first disease recurrence/relapse (local/regional recurrence and/or distant metastasis) or death from any cause whichever comes first. |
From randomization or enrollment to disease recurrence or death, up to 5 years
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Overall survival
時間枠：From randomization or enrollment to death, up to 5 years
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The overall survival is the length of time from randomization (or enrollment for patients in the prospective cohort) that patients enrolled in the study are still alive. |
From randomization or enrollment to death, up to 5 years
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Metastases-free survival
時間枠：From randomization or enrollment to metastases onset or death, up to 5 years
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The metastases-free survival is the length of time during and after the treatment for cancer that a patient is still alive and the cancer has not spread to other parts of the body. |
From randomization or enrollment to metastases onset or death, up to 5 years
|
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Incidence of adverse events
時間枠：Throughout study completion, up to 5 years
|
The National Cancer Institute-Common Terminology Criteria for Adverse Events version 5 (NCI-CTCAE v5) is widely accepted in the community of oncology research as the leading rating scale for adverse events. This scale, divided into 5 grades (1 = "mild", 2 = "moderate", 3 = "severe", 4 = "life-threatening", and 5 = "death") determined by the investigator, will make it possible to assess the severity of the disorders. Safety and tolerability (NCI-CTCAE v5.0) will be assessed through the incidence of adverse events, treatment-related adverse events, serious adverse events (SAEs); and death. |
Throughout study completion, up to 5 years
|
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Quality of life questionnaire - Core 30 (QLQ-C30)
時間枠：At baseline, end of treatment (up to week 12), 4 months, 6 months, 1 year and 2 years
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Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials. The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. |
At baseline, end of treatment (up to week 12), 4 months, 6 months, 1 year and 2 years
|
協力者と研究者
スポンサー
協力者
捜査官
- 主任研究者：Florence DUFFAUD, MD、La TIMONE University Hospital
研究記録日
主要日程の研究
研究開始 (実際)
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
追加の関連 MeSH 用語
その他の研究ID番号
- UC-SAR-2212
- 2023-506350-21-00 (Ctis)
- 2023 (米国 NIH グラント/契約)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
Individual Participant Data will not be shared at an individual level. Those data will be part of the study database including all enrolled patients.
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
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。