Personalize (Signature Driven) Neoadjuvant Chemotherapy Trial for Patients With Resectable Borderline Pancreatic Ductal Adenocarcinoma. (NEOPREDICT)
a Multicenter Phase II Trial Using Transcriptomic Signatures to Personalize Neoadjuvant Chemotherapy for Patients With Resectable Borderline Pancreatic Ductal Adenocarcinoma.
Pancreatic ductal adenocarcinoma (PDAC) exhibits significant heterogeneity, making the optimal choice of chemotherapy challenging. While targeted therapies benefit from companion biomarkers, few tools exist to guide the selection of cytotoxic chemotherapy. Transcriptomic signatures now allow for the prediction of sensitivity to cytotoxic agents. Several molecular classifications (such as basal-like, classical, etc.) have been established and correlated with prognosis, but they are rarely used in clinical practice. The PaCaOmics program has developed robust predictive signatures, grouped under the name Pancreas-View Signature, capable of analyzing FFPE samples using minimal material.
Locally advanced or borderline resectable pancreatic cancer (BR-PDAC) accounts for approximately 20% of cases. Neoadjuvant chemotherapy (NAC) has become the standard of care, improving R0 resection rates and overall survival. The two main chemotherapy regimens used are mFOLFIRINOX and GEM/NAB-paclitaxel, which show comparable efficacy and toxicity profiles. However, no clear consensus exists on the superiority of one over the other. Therefore, predictive biomarkers are crucial to help select the most appropriate neoadjuvant regimen, avoid unnecessary toxicities, and maximize the chances of curative surgery. The NEOPREDICT trial aims to evaluate the efficacy of treating patients with borderline resectable PDAC identified with a GEM+ sensitivity transcriptomic signature with GEMCITABINE + NAB-PACLITAXEL regimen compared to standard of care mFOLFIRINOX as NAC.
調査の概要
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：Falilatou SAKA
- 電話番号：0658636325
- メール：prodige104.neopredict@ffcd.fr
研究場所
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Clichy、フランス
- Hopital Beaujon
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コンタクト：
- Maher AKEZ
- メール：maher.akez-ext@aphp.fr
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主任研究者：
- Louis De Mestier, MD
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Marseille、フランス
- Institut Paoli Calmettes
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コンタクト：
- Christophe BOUVIER
- メール：BOUVIERC3@ipc.unicancer.fr
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主任研究者：
- Brice CHANEZ, MD
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Pierre-Bénite、フランス
- Hopital Lyon Sud
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コンタクト：
- Maëlys SIEGWALD
- メール：maelys.siegwald@chu-lyon.fr
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主任研究者：
- Marion CHAUVENET, MD
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Saint-Priest-en-Jarez、フランス
- Hopital Nord Chu Saint Etienne
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主任研究者：
- Nicolas WILLIET, MD
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コンタクト：
- Fabrice DI PALMA, PhD
- メール：fabrice.dipalma@chu-st-etienne.fr
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Toulouse、フランス
- Hopital Rangueil
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主任研究者：
- Nadim FARES, MD
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コンタクト：
- Caroline GREGOIRE
- メール：gregoire.c@chu-toulouse.fr
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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:
- Borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) defined by National Comprehensive Cancer Network (NCCN) criteria v2.2025 on contrast-enhanced CT-scan (including non-contrast acquisition, pancreatic phase and portal venous phase), with stage confirmed by a local pancreatic expert review board including at least medical oncologist/onco-gastroenterologist, pancreatic surgeon and pancreatic expert radiologist. No central review is required,
- Measurable pancreatic lesion according to RECIST 1.1 (CT scan or MRI < 28 days),
- WHO PS 1 or 0,
- Histologically proven pancreas ductal adenocarcinoma,
- Available FFPE from pancreatic tumor sample with > 10% of tumor cells (assessed by a local expert pancreatic pathologist),
- No prior chemotherapy or radiation for pancreatic cancer (except one cycle of mFOLFIRINOX during waiting time for GEM + signature) or resection of pancreatic cancer,
- Age ≥18 years old and ≤ 80 years old if geriatric standardized evaluation validates the study chemotherapy regimen administration for patients between 75-80,
- Written informed consent obtained from patient before any protocol related intervention,
- Acceptation and ability to conform to the protocol requirement during all the duration of the investigation including treatment, scheduled visits, clinical and biological examinations and follow up,
- Adequate organ function, as defined by the following:
- AST and ALT < 3.5 x upper limit of normal (ULN),
- Total serum bilirubin < 3 x ULN, (for patients with total serum bilirubin between 1.5 and 3 x ULN, the dose of irinotecan will be adjusted in accordance with the SmPC).
- Serum albumin >30 g/L,
- Hemoglobin >9.0 g/dl,
- Absolute neutrophil count (ANC) >1.5 G/L,
- Platelets >100 G/L,
- Creatinine clearance > 50 mL/min (according to CKD-EPI),
- Normal Kalemia, calcemia, magnesemia
- Women of childbearing potential must agree to use contraception during treatment and for at least 15 months after discontinuation of the experimental treatments. Men who have sexual relationship with women of childbearing potential must agree to use contraception during treatment and for at least 12 months after discontinuation of the experimental treatments.
- Patient affiliated to French social security
Exclusion Criteria:
- Strictly resectable or locally advanced PDAC according to NCCN criteria,
- Distant metastases (including inter aortic lymph nodes),
- Any condition that contraindicates the use of IRINOTECAN, OXALIPLATIN, 5FU, GEMCITABINE or NAB-PACLITAXEL,
- Partial or complete DPD deficiency (uracilemia ≥ 16 ng/mL),
- Any progressive pathology not stabilized over the past 6 months: liver impairment, renal impairment, respiratory or cardiac failure.
- Other concomitant cancer or a history of cancer during the previous 3 years, except for localized cancer in situ, basal or squamous cell skin cancer adequately treated,
- Other interventional clinical trial except for non-interventional trial (ie not modifying 1-year EFS),
- QT/QTc (Fredericia Correction) interval > 450 msec for men and > 460 msec for women,
- Pregnant or breastfeeding woman,
- Known Gilbert's syndrome or known homozygosity for UGAT1A1*28 polymorphism,
- Treatment with millepertuis,
- Uncompensated asthma,
- Potentially severe infection < 7 days,
- Inflammatory bowel disease and/or intestinal obstruction,
- Known severe allergy to contrast dye (for CT or MRI) without possible substitution,
- Hypersensitivity to the active substance or to one of the excipients of one of the study treatments,
- Treatment with brivudine within 4 weeks prior to the administration of protocol treatment,
- Concomitant treatment with a strong inhibitor (i.e. ketoconazole) or inducer (i.e. rifampicin, carbamazepine, phenobarbital, phenytoin, apalutamide) of cytochrome P450 3A4 or 2C8 (CYP3A4 or CYP2C8),
- Patient who has received a live attenuated vaccine (against yellow fever, chickenpox, shingles, measles, mumps, rubella, tuberculosis, rotavirus) in the 6 weeks prior to randomization,
- Patient with sensitive peripheral neuropathy with functional discomfort,
- Impossibility of undergoing medical monitoring during the trial for geographical, social, or psychological reasons,
- Patient who is under judicial protection (patient who is legally institutionalized or under guardianship or curatorship) or not able to give consent. (as refered at art. art. L. 1121-6, art. L. 1121-8, art. L. 1121-8-1 du Code de la Santé Publique)
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：NAB-PACLITAXEL - GEMCITABINE Arm
NAB-PACLITAXEL 125 mg/m2 on day 1, 8 and 15 + GEMCITABINE 1000 mg/m2 on day 1, 8 and 15.
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NAB-PACLITAXEL 125 mg/m2 (30 min infusion) on day 1, 8 and 15.
GEMCITABINE 1000 mg/m2 over 30 min infusion on day 1, 8 and 15.
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アクティブコンパレータ：mFOLFIRINOX Arm
Oxaliplatin 85 mg/m2 + Folinic acid 400 mg/m2 (or Leucovorin 200 mg/m²) + Irinotecan 180 mg/m2 (150 mg/m2 for older patient after SGA) + 5-FU 2400 mg/m2 as a continuous IV infusion over 46 hours
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Oxaliplatin 85 mg/m2 as a 2-hour IV infusion on day 1. Folinic acid 400 mg/m2 (or Leucovorin 200 mg/m²) as a 2-hour IV infusion (after end of oxaliplatin), in Y with irinotecan on day 1. Irinotecan 180 mg/m2 (150 mg/m2 for older patient after SGA) for 1h30 on day 1 (30 min after beginning of folinic acid). 5-FU 2400 mg/m2 as a continuous IV infusion over 46 hours, from day 1. |
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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Event Free Survival
時間枠：at 1 year after randomization
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Event Free Survival (EFS) will be calculated from the date of randomization to the date at which the first event occurs.
Patients alive without any event will be censored at the date of last news.Events to be considered for the endpoint will be: Disease progression, No pancreatic resection (all causes), Death whatever the cause, Grade IV febrile neutropenia or grade IV diarrhea during NAC.
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at 1 year after randomization
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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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Objectif Response Rate (ORR)
時間枠：At 16 weeks after randomization
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Objective Response rate (ORR) will be evaluated with RECIST 1.1 criteria by the investigator regarding the scans during the NAC.
The objective response rate is defined as % of patients with a complete or a partial response.
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At 16 weeks after randomization
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協力者と研究者
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
追加の関連 MeSH 用語
その他の研究ID番号
- PRODIGE 104 A (FFCD 2307)
- 2024-519753-11-00 (Ctis)
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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