Prospective Cohort of Patients Treated Using Neoadjuvant Modified FOLFIRINOX 6 Cycles for Potentially Resectable Pancreatic Duct Adenocarcinoma, Candidate for Participation in the PANACHE02 Clinical Trial PANACHE02-SC
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 820
- 试验地点
- 1
- 主要终点
- factors and/or multifactorial biomarkers signature predictive of success of the complete therapeutic sequence
研究概览
简要总结
The aim of our study is to build up biological, radiological and tissue collections so as to identify, at the time of diagnosis of pancreatic adenocarcinoma, multifactorial factors and/or biomarkers (tissue, plasma, radiomic) predictive of the success of the complete therapeutic sequence.
So we can distinguish 3 biological collections here :
- Collection for ctDNA assay on STRECK tubes
- Collection on PAXgene tubes
- Tissus collection
Considering the biology collection for ctDNA assay : blood samples will be taken on specific tubes before the start of neoadjuvant chemotherapy (C1), Before C2 and after C4 of neoadjuvant chemotherapy. For ctDN assay, 2x 10ml STRECK tubes will be taken at each point for each patient.
At the end of the study, aliquots will be sent to INSERM unit U1245 to be analyzed
Considering the biology collection on PAXgene tubes : 2,5 ml blood samples will be taken in PAXgene blood RNA tube before C1 for each patient
Considering tissue collection: pre-chemotherapy biopsies and surgical specimens will be preserved after resection. Tissue sample will be collected and preserved in the tumor bank of Rouen university hospital,
By collecting data for all screened patients (complete sequence in PANACHE02, NT failure (progression), randomization failure after surgery) at diagnosis (clinicobiological data, pre-NT biopsies, blood samples and imaging data) we first aim to refine patient selection for NT benefit with a multivariable signature approach and to identify biomarkers (blood, imaging) monitoring during the neoadjuvant phase that could be predictive of early detection for NT treatment failure.
We therefore believe that the constitution of such cohort is critical to address numerous unmet needs.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pancreatic adenocarcinoma, confirmed by a histocytological analysis
- •Potentially resectable pancreatic adenocarcinoma (according to the NCCN classification; Version 2.2017). Resecability is evaluated on arterial-phase and portal-phase IV contrast-enhanced multislice CT scan of the pancreas (slice thickness: 2.5 mm), as evaluated in a multidisciplinary staff meeting including at least one radiologist and one expert surgeon.
- •No previous chemotherapy
- •Age 18 or over
- •PS Grade 0 or 1
- •Absolute neutrophil count > 1,500 mm3 platelet count > 100,000 mm3 creatinine clearance (according MDRD equation) > 50 ml/min, haemoglobin level > 10 g/dl (transfusions are authorized)
- •Women of child-bearing age not having undergone a hysterectomy or tubal ligation - requirement for a pregnancy test (abnormal serum or urine beta-HCG level) before inclusion.
- •Provision of informed, written consent
排除标准
- •Pancreatic adenocarcinoma defined as locally advanced non-resectable or metastatic.
- •Dihydropyrimidine dehydrogenase complete deficiency (uracilemia ≥ 150 ng/ml)
- •Surgical or anaesthesiological contra-indications:
- •non-controlled congestive heart failure - non-treated angina - recent myocardial infarction (in the previous year) - non-controlled AHT (SBP >160 mm or DBP > 100 mm, despite optimal drug treatment), long QT
- •major non-controlled infection
- •severe liver failure
- •Any medical, psychological or social situation that (in the investigator's opinion) could limit (i) the patient's compliance with the protocol or (ii) the ability to obtain or interpret data
- •Pregnant or breastfeeding women and women of child-bearing age not using effective means of contraception
结局指标
主要结局
factors and/or multifactorial biomarkers signature predictive of success of the complete therapeutic sequence
时间窗: from enrollment to the first cycle of adjuvant treatment up to 2 months
In relation with the primary objective the primary endpoint of the PANACHE02 screening cohort study is the success for the complete therapeutic sequence defined by the administration of at least 4 cycles of neoadjuvant modified FOLFIRINOX following by pancreatic tumor resection and at least one cycle of adjuvant treatment. A patient evaluable for the primary endpoint is a patient for whom we the success or the failure of the complete therapeutic sequence. A patient in success for the complete therapeutic sequence is a patient with an administration of at least 4 cycles of neoadjuvant modified FOLFIRINOX following by pancreatic tumor resection and at least one cycle of adjuvant treatment. A patient in failure for the complete therapeutic sequence is a patient with an administration of less than 4 cycles of neoadjuvant modified FOLFIRINOX and/or no resection and/or no adjuvant treatment administration.
次要结局
- value of the tumour response(from enrollment to the end of follow-up period at 28 months)
- Number of patients with complete neoadjuvant sequence(from enrollment to the end of follow-up period at 28 months)
- surgical morbidity and mortality rates(from enrollment to 90 days post operatively)
- Overall Survival (OS) in the overall population and according to the complete therapeutic sequence status(through study completion, an average of 76 months)
- prognostic value of ctDNA at diagnosis for OS(through study completion, an average of 76 months)
- prognostic value of ctDNA at diagnosis for event free survival,(through study completion, an average of 76 months)
- tissue, serum and imaging libraries (Biological database development)(through study completion, an average of 76 months)
- factors associated with early recurrence for patients resected (< 12 months after surgical resection).(from surgical resection to the end of follow-up period at 28 months)
- the rate of patients with access to adjuvant treatment(from enrollment to the adjuvant treatment period, an average of 5 months)
- factors at diagnosis associated with the access to adjuvant treatment(from enrollment to the adjuvant treatment period at 5 months)
- safety and tolerance of the neoadjuvant chemotherapy(from enrollment to 90 days post operatively)
- overall morbidity of the neoadjuvant chemotherapy(from enrollment to 90 days post operatively)
- evolution of health-related quality of life(from enrollment to the end of follow-up period at 28 months)