Resected Pancreatic Adenocarcinoma
Conditions
Brief summary
Induction mFOLFIRINOX has become the standard in the management of locally advanced and borderline adenocarcinoma. Following the results of the PREOPANC-01 JASP-05, NEONAX studies it is expected that the neoadjuvant approach will be the standard strategy soon in patients with resectable PAC. The results of the PANACHE-01 trial confirm the feasibility of the neoadjuvant approach in the setting of resectable adenocarcinoma. Two randomized phase III studies, on the same design as PANACHE-01 are currently underway comparing neoadjuvant and adjuvant chemotherapy with mFOLFIRINOX for resectable PAC, (Alliance AO21806, NCT04340141; PREOPANC3, NCT04927780). Despite the improvement of oncosurgical management, recurrence of PAC soon after resection occurs frequently, leading to the dismal prognosis and unnecessary surgery-related loss of quality of life. Thus, there is urgent need for development of innovative and new strategies to decrease postoperative recurrence. Important residual tumor load after NAT suggests a primary resistance of the tumor or the selection of resistant clones. The most innovative aspect of this study will be to adapt the adjuvant chemotherapy strategy to the pathological response (downstaging) in patients who will have R0-R1 resection after neoadjuvant mFOLFIRINOX, taking into account the chemoresistance/sensibility status of the tumor.
Interventions
DRUGGem/Nabpaclitaxel infusion
Downstaging and pathological response is empirically define as T1-2/N0/R0 status. If the anatomopathological analysis shows a lesion classified as T3-4 or N+ or R1, an adjuvant chemotherapy based on Gemcitabine with Nab Paclitaxel will be proposed for a period of 3 months.
DRUGmFOLFIRINOX infusion
Downstaging and pathological response is empirically define as T1-2/N0/R0 status. In that setting the patients will receive mFOLFIRINOX adjuvant chemotherapy 3 months.
Sponsors
University Hospital, Rouen
Partenariat de Recherche en Oncologie DIGEstive - PRODIGE
Federation de recherche en chirurgie digestive (FRENCH)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically confirmed resected pancreatic adenocarcinoma (R0 or R1) that has received 3 months of neoadjuvant mFOLFIRINOX, including anatomically resectable and borderline resectable tumors, in accordance with the definitions and therapeutic considerations provided in the TNCD (2024) and ESMO (2023) guidelines. 2. Performance status ECOG 0 or 1 3. CA 19-9 level ≤ 200 U/ml 4. Age 18 years or over 5. Absolute neutrophil count \> 1,500 mm³, platelet count \> 100,000 mm³, creatinine clearance (according to MDRD equation) \> 50 ml/min, haemoglobin level \> 10 g/dl (transfusions are authorized) 6. Women of childbearing potential (a woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile): with highly effective contraception (Cf. CTCG): combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomised partner, sexual abstinence) since 1 month, during chemotherapy treatment and for 15 months after cessation of chemotherapy treatment, and a negative blood pregnancy test for β-HCG at inclusion as well as pregnancy tests before each cycle of adjuvant chemotherapy, then monthly throughout the study until 15 months after the end of exposure to systemic treatment. Women permanently sterile (hysterectomy, bilateral salpingectomy or bilateral oophorectomy). Postmenopausal women: A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. 7. For men participating in the study, contraception is required during the trial and for 12 months after stopping chemotherapy treatment. 8. Patient affiliated with, or beneficiary of, a social security (national health insurance) plan 9. Patient able to comply with the study protocol, in the investigator's judgment 10. Read and understood the information letter and signed the consent form
Exclusion criteria
1. Metastatic PAC on post-operative imaging 2. Cholangiocarcinoma, ampullary carcinoma or other non-PAC pancreatic tumors 3. Non-controlled congestive heart failure, non-treated angina, recent myocardial infarction (in the previous year), non-controlled AHT (SBP \> 160 mm Hg or DBP \> 100 mm Hg, despite optimal drug treatment), long QT 4. Major non-controlled infection, chronic infectious diseases, immune deficiency syndromes 5. Premalignant hematologic disorders, e.g. myelodysplastic syndrome 6. Severe liver failure 7. Past or current history of malignancies except for the indication under this study and curatively treated basal and squamous cell carcinoma of the skin, in situ carcinoma of the cervix, other malignant disease without recurrence after at least 2 years of follow-up 8. Any medical, psychological or social situation that (in the investigator's opinion) could limit the patient's compliance with the protocol or the ability to obtain or interpret data or to understand the conditions required for his/her participation in the protocol or render him/her unable to give informed consent 9. Pregnant or breastfeeding women and women of childbearing age not using effective means of contraception 10. Person participating in another interventional research having the same primary endpoint 11. Person deprived of liberty by an administrative or judicial decision or person placed under judicial protection, under guardianship or curatorship 12. Uracilemia ≥ 150 ng/ml (suggestive of complete DPD deficiency) 13. Contraindication to study adjuvant chemotherapy treatments in accordance with the SmPCs of the products used in this trial (Gemcitabine, Nab-Paclitaxel, Oxaliplatin, Folinic Acid or Leucovorin, Irinotecan, Fluorouracil)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Free Survival | from enrollment up to 5 years | The primary efficacy endpoint is the Disease Free Survival at 2 years (DFS), defined as the time from randomization to locoregional recurrence, occurrence of distant metastases or second pancreatic cancer, or death (all causes) whichever occurred first. Patients free of events will be censored at the date of the last disease evaluation either during study treatment period or during follow-up period |
| Overall Survival | from enrollment up to 7 years | The primary efficacy endpoint is the Overall Survival at 3 years(OS), defined as the time from randomization to the death from any cause. Alive patient will be censored at last date known to be alive either during study treatment period or during follow-up period |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and grade for Adverse Events (AEs) | from enrollment up to 7 years | drug related AEs, drug related AE leading to dose reduction or discontinuation during treatment, SAE and SUSAR, according to NCI-CTCAE V5.0. |
| metastatic recurrence free survival in both arms | from enrollment up to 7 years | Time to metastatic recurrence defined as the time from randomization to occurrence of distant metastases. |
| rate of patients with early recurrence | from enrollment up to 5 years | Early recurrence \< 6 months after surgical randomization |
| evolution of the health-related quality of life | from enrollment up to 7 years | Health related quality of life EORTC QLQ-C30 questionnaire (European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire - Core 30). Scale rated from 0 to 100. |
| Correlation of tumour response with TNM classification | from enrollment up to 7 years | TNM classification : T- the extent of the primary tumour (T1-T4 Increasing size) N- the absence N0 or presence (N1-N2) and extent of regional lymph node metastasis M- the absence (M0) or presence (M1) of distant metastasis |
| Correlation of tumour response with Residual Tumour (R) Classification | from enrollment up to 7 years | Residual Tumour (R) Classification : R0 No residual tumour R1 Microscopic residual tumour |
Countries
France
Contacts
CONTACTLilian SCHWARZ, PUPH
CONTACTMylene HERVET
Outcome results
None listed