Pancreatic Adenocarcinoma Resectable

This is an open master platform trial, which includes multi neo-adjuvant treatment trials, multi-center, national. This platform trial evaluates the major pathological response rate (mPR) after surgery. Intervention: The procedure consists of administering a neoadjuvant treatment and then performing pancreatic surgery. The POWER platform trial aims to study several neoadjuvant treatments prior to surgery. They will be described in each sub-study, in appendix. The surgery will be performed on one day and the end of the treatment is the safety visit post-surgery (90 days after surgery).

Pancreatic adenocarcinoma (PAAD) is a leading cause of cancer-related deaths worldwide. Although surgical resection can be curative, the 5-year overall survival (OS) rate after resection alone is approximately 20%. Adjuvant chemotherapy can improve survival outcomes in patients with resected PAAD. This study will explore the application of ctDNA MRD in guiding adjuvant therapy in these patients. This prospective, randomized, interventional trial will evaluate a ct-DNA MRD-guided adjuvant therapy strategy in PAAD patients who have undergone radical resection at our institution. Prior to adjuvant chemotherapy, patients will be randomized (1:1) to either the experimental arm (Arm A) or the control arm (Arm B). Arm A will receive ct-DNA MRD-guided therapy, while Arm B will receive non-ctDNA-driven standard of care post-operative adjuvant therapy. In Arm A, patients will receive a physician-selected, guideline-recommended adjuvant therapy regimen in 12-week cycles. ctDNA MRD will be assessed before the end of first cycle and at weeks 8 and 11. If two consecutive post-treatment MRD tests are negative, therapy will be "de-escalated" (discontinued) with regular follow-up as determined by the clinician. Otherwise, another treatment cycle will be administered, with the same MRD assessment. Following the second cycle, patients without two negative MRD results (only tested at week 8 and week 11 within each cycle) will "escalate" to a longer duration of chemotherapy (comparing to the 6-month standard of care) at the clinician's discretion. Treatment will continue until disease progression, intolerance, or study termination. Arm B will receive standard post-operative adjuvant therapy for a duration recommended by CSCO guidelines (typically 6 months), followed by regular follow-up every 8 weeks. The primary endpoint is to compare the prognosis, tolerability, and treatment completion rates between the two arms.