A Trial Using Transcriptomic Signatures to Personalize Neoadjuvant Chemotherapy (NAC) for Patients With Resectable Borderline Pancreatic Adenocarcinoma (PDAC) (PRODIGE 104 B)
A Multicenter Randomized Phase II Trial Using Transcriptomic Signatures to Personalize Neoadjuvant Chemotherapy (NAC) for Patients With Resectable Borderline Pancreatic Adenocarcinoma (PDAC)
Pancreatic cancer exhibits significant heterogeneity, which poses a major challenge in selecting the best treatment for patients from the very beginning of care. Modern oncology recognizes the use of companion biomarkers to guide targeted therapy or immune checkpoint inhibitors. However, with regard to chemotherapy-which has long been the cornerstone of cancer treatment and remains crucial for most cancers-few predictive tests are available to guide the choice between monotherapy and combination chemotherapy.
Patients included in the PRODIGE 104 B - NEOPREDICT study will be those for whom the GEM transcriptomic signature is negative. This population will be treated according to the standard strategy and will be followed clinically and biologically to describe and identify the characteristics specific to this subgroup, and to compare the usual prognostic factors of this population with those of the GEM-positive population included in the parallel PRODIGE 104 A - NEOPREDICT study
調査の概要
詳細な説明
Transcriptomic Signature for Patient Stratification and Prediction of Chemotherapy Sensitivity Transcriptomic signatures, derived from RNA-sequencing, capture unique patterns of gene expression that reflect the molecular phenotype of a tumor and can indicate its potential sensitivity or resistance to chemotherapeutic agents. Over the past decade, several molecular classifications of PDAC have been established (Collisson, Moffitt, Bailey), consistently distinguishing two major tumor subtypes: basal-like (poor prognosis) and classical (better prognosis). While these classifications provide strong prognostic information, they have not reliably predicted chemotherapy response in clinical practice.
Recent advances from the Dusetti/Iovanna research group have led to the development of robust transcriptomic signatures capable of predicting sensitivity to gemcitabine, irinotecan, 5-FU, oxaliplatin, and paclitaxel. These signatures-collectively referred to as Pancreas-View-were generated using preclinical models (PDX, organoids, primary cultures) and have been clinically validated, notably the gemcitabine-sensitivity signature in two retrospective cohorts and in the prospective PRODIGE 24 trial. Importantly, these signatures can be performed on FFPE-derived RNA with minimal material and rapid turnaround, making them compatible with real-world decision-making in the neoadjuvant setting.
Position of the Study Within Current Knowledge Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal disease due to late diagnosis, limited actionable biomarkers, and the modest efficacy of targeted and immunotherapeutic approaches. Its incidence is rising in Western countries, and without improved strategies, PDAC is projected to become the second leading cause of cancer-related death by 2040.
Borderline-resectable PDAC accounts for approximately 20% of cases and typically requires complex multidisciplinary management. Neoadjuvant chemotherapy (NAC)-now an international standard in BR-PDAC-offers several advantages: improved R0 resection rates, treatment of occult micrometastatic disease, and avoidance of futile surgery in rapidly progressing tumors.
Two main NAC regimens are currently used: mFOLFIRINOX and Gemcitabine + Nab-Paclitaxel. However, comparative studies in non-metastatic PDAC have not demonstrated a clear superiority of one regimen over the other, though their toxicity profiles differ substantially. As a result, selecting the optimal chemotherapy strategy remains challenging.
There is therefore a strong need for predictive biomarkers capable of guiding neoadjuvant regimen selection. The NEOPREDICT program positions itself directly within this unmet clinical need, evaluating the use of a transcriptomic gemcitabine-sensitivity signature to personalize treatment.
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前：PAKRADOUNI
- 電話番号：+33 4 91 22 37 78
- メール：drci.up@ipc.unicancer.fr
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) as defined by the National Comprehensive Cancer Network (NCCN) v2.2025 criteria, identified on contrast-enhanced CT scan and reviewed by a local multidisciplinary pancreatic expert board including at least a medical oncologist / onco-gastroenterologist, a pancreatic surgeon, and an expert pancreatic radiologist. No central review required.
- WHO Performance Status 0-1.
- Histologically confirmed pancreatic ductal adenocarcinoma, including histological variants.
- Patient included-but not randomized-in the PRODIGE 104 A NEOPREDICT study due to a negative gemcitabine sensitivity signature (GEM-).
- Negative gemcitabine transcriptomic signature (test centrally performed in PRODIGE 104 A NEOPREDICT).
- No prior chemotherapy or radiotherapy for pancreatic cancer, and no previous definitive pancreatic cancer resection (except one cycle of mFOLFIRINOX administered while awaiting the signature result).
- Age > 18 years and < 80 years, with the possibility to include patients aged 75-80 if a standardized geriatric assessment confirms eligibility for the study chemotherapy regimen.
- Ability and willingness to comply with protocol requirements during the entire study period (treatment, scheduled visits, clinical and biological examinations, follow-up).
- Patient's non-opposition to participation in the study.
- Affiliation to the French national health insurance system.
Exclusion Criteria:
- Strictly resectable or locally advanced PDAC according to NCCN criteria.
- Distant metastases, including inter-aortocaval lymph nodes.
- Any condition contraindicating the use of irinotecan, oxaliplatin, or 5-FU.
- Complete dihydropyrimidine dehydrogenase (DPD) deficiency.
- Any uncontrolled or unstable medical condition within the past 6 months (e.g., hepatic, renal, respiratory, or cardiac insufficiency).
- Another concomitant malignancy or history of cancer within the past 3 years, except for adequately treated carcinoma in situ of the cervix or basal/squamous cell skin carcinoma.
- Pregnancy or breastfeeding.
- Patients under legal protection, guardianship, curatorship, or under judicial/administrative protection.
- Patients receiving psychiatric care or unable to provide consent.
- Inability to comply with medical follow-up for geographical, social, or psychological reasons.
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：なし
- 介入モデル：単一グループの割り当て
- 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 |
|---|---|
|
実験的：single arm - mFOLFIRINOX
Patients GEM- with BR-PDAC receiving standard mFOLFIRINOX according to clinical guidelines.
|
Patients with borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) who are negative for the gemcitabine sensitivity transcriptomic signature (GEM-) receive neoadjuvant mFOLFIRINOX chemotherapy as standard of care.
This observational cohort follows patients prospectively without modifying routine management.
|
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 |
|---|---|---|
|
Primary Outcome Measure
時間枠：From treatment initiation through 1 year
|
Event-Free Survival is defined as the time from the start of treatment to the occurrence of any of the following events:
Participants without an event will be censored at the date of last follow-up. |
From treatment initiation through 1 year
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Objective Response Rate (ORR)
時間枠：During neoadjuvant chemotherapy (up to 16 weeks)
|
Percentage of participants achieving a complete response or partial response per RECIST 1.1 criteria.
|
During neoadjuvant chemotherapy (up to 16 weeks)
|
|
Overall Survival (OS)
時間枠：From treatment initiation through study completion (up to 18 months)
|
Time from start of treatment to death from any cause.
|
From treatment initiation through study completion (up to 18 months)
|
|
Progression-Free Survival (PFS)
時間枠：From treatment initiation through study completion (up to 18 months)
|
For non-operated patients: time from treatment initiation to disease progression or death from any cause.
|
From treatment initiation through study completion (up to 18 months)
|
|
Recurrence-Free Survival (RFS)
時間枠：From treatment initiation through study completion (up to 18 months)
|
For operated patients: time from treatment initiation to first local or metastatic recurrence or death.
|
From treatment initiation through study completion (up to 18 months)
|
|
Disease Control Rate (DCR)
時間枠：During neoadjuvant chemotherapy (up to 16 weeks)
|
Percentage of patients achieving complete response, partial response, or stable disease.
|
During neoadjuvant chemotherapy (up to 16 weeks)
|
|
Tumor Regression Grade (TRG)
時間枠：At time of surgery
|
Pathologic tumor response assessed using Ryan's simplified Tumor Regression Grade (TRG 1-3) on the resected primary tumor.
|
At time of surgery
|
|
Postoperative Complications (Clavien-Dindo Classification)
時間枠：Within 60 days after surgery
|
Postoperative complications graded from I to V according to Clavien-Dindo.
|
Within 60 days after surgery
|
|
Time to Recurrence (TTR)
時間枠：Up to 18 months
|
Time from treatment initiation to first recurrence (local or metastatic) or death related to cancer.
|
Up to 18 months
|
|
Quality of Life (EORTC QLQ-C30 )
時間枠：From baseline through study completion (up to 18 months)
|
Change over time in the Global Health Status/Quality of Life scale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30).
|
From baseline through study completion (up to 18 months)
|
|
Completion Rate of Neoadjuvant Chemotherapy (NAC)
時間枠：End of the 4-month NAC period
|
Percentage of participants who completed all 8 cycles of mFOLFIRINOX (regardless of dose modifications).
|
End of the 4-month NAC period
|
|
Adverse Events and Toxicities (NCI-CTCAE v5.0)
時間枠：Before each chemotherapy cycle (Weeks 0-16)
|
Incidence and severity of treatment-related toxicities graded according to NCI-CTCAE v5.0.
|
Before each chemotherapy cycle (Weeks 0-16)
|
|
ime to First Deterioration in Global Health Status
時間枠：From treatment initiation through study completion (up to 18 months)
|
Time to first deterioration of more than 5 points from baseline in the EORTC QLQ-C30 global health status score.
|
From treatment initiation through study completion (up to 18 months)
|
|
Pancreatic Cancer-Specific Quality of Life (EORTC QLQ-PAN26)
時間枠：From baseline through study completion (up to 18 months)
|
Change over time in symptom and functional scores assessed using the EORTC QLQ-PAN26 pancreatic
|
From baseline through study completion (up to 18 months)
|
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
キーワード
その他の研究ID番号
- PRODIGE 104 B-NEOPREDICT-IPC 2
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?
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
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