Risk-adapted Adjuvant Chemotherapy Guided by the Tumour Stage for Operated Pancreatic Adenocarcinoma Following Neoadjuvant Chemotherapy With mFOLFIRINOX

NCT ID: NCT07044453

Last Updated: 2025-07-01

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 390 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-30
• Study Completion Date: 2032-09-30

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.

Conditions

Resected Pancreatic Adenocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Experimental group - Arm A:

Adjuvant chemotherapy guided by pathological analysis (downstaging)

• pT1-2/N0/R0 status: 3 months mFOLFIRINOX adjuvant chemotherapy (no change in chemotherapy regimen compared to neoadjuvant setting)
• pT3-4 or N+ or R1 status: 3 months Gemcitabine with NabPaclitaxel adjuvant chemotherapy (change in chemotherapy regimen compared to neoadjuvant setting).

Group Type: EXPERIMENTAL

Gem/Nabpaclitaxel infusion

Intervention Type: DRUG

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.

mFOLFIRINOX infusion

Intervention Type: DRUG

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.

Control group - Arm B

3 months mFOLFIRINOX adjuvant chemotherapy regardless of pathological analysis

Group Type: ACTIVE_COMPARATOR

mFOLFIRINOX infusion

Intervention Type: DRUG

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.

Interventions

Gem/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.

Intervention Type: DRUG

mFOLFIRINOX 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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Histologically confirmed resected pancreatic adenocarcinoma (R0 or R1) who 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. Performans status ECOG 0 or 1

3. CA 19-9 level ≤ 200 U/ml

4. Age 18 or over

5. 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)

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 by B-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 and 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 post-menopausal 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 or DBP > 100 mm, 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 to the protocol or unable him/her to give an informed consent

9. Pregnant or breastfeeding women and women of child-bearing age not using effective means of contraception

10. Person participating to another interventional research having the same primary endpoint

11. Person deprived of liberty by an administrative or judiciary 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 SmPC's of the products used in this trial (Gemcitabine, Nab-Paclitaxel, Oxaliplatin, Folinic Acid or Leucovorin, Irinotecan, Fluorouracil) -

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Partenariat de Recherche en Oncologie DIGEstive - PRODIGE

UNKNOWN

Sponsor Role: collaborator

Federation de recherche en chirurgie digestive (FRENCH)

UNKNOWN

Sponsor Role: collaborator

University Hospital, Rouen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

CHU de Rouen

Rouen, , France

Countries

France

Central Contacts

Lilian SCHWARZ, PUPH

Role: CONTACT

lilian.schwarz@chu-rouen.fr

+332 32 88 84 18

Mylene HERVET

Role: CONTACT

mylene.hervet@chu-rouen.fr

Facility Contacts

Lilian SCHWARZ, PUPH

Role: primary

lilian.schwarz@chu-rouen.fr

+332 32 88 84 18

Other Identifiers

2024-519048-33-00

Identifier Type: CTIS

Identifier Source: secondary_id

2021/0377/HP

Identifier Type: -

Identifier Source: org_study_id