Ampullary Cancer, Pancreas Adenocarcinoma, Pancreas Cancer, Pancreatic Cancer Resectable, Periampullary Cancer, Periampullary Carcinoma Resectable
Conditions
Keywords
Pancreatic cancer, Neoadjuvant chemotherapy, Pancreaticoduodenectomy
Brief summary
Adjuvant chemotherapy after surgery significantly improved the survival of pancreatic cancer (PC) patients, but there is a problem that only about 50% of patients start adjuvant chemotherapy after pancreatectomy. Neoadjuvant chemotherapy might control potential metastatic lesions which are not being detected in early disease status and improve the R0 resection rate. In addition, it prevents futile surgery by selecting patients with rapid progression of disease. Furthermore, compared to chemotherapy administered after surgery, more patients can complete the planned chemotherapy schedule in neoadjuvant setting. There are still few studies worldwide that prospectively explored the efficacy of neoadjuvant chemotherapy in resectable PC and periampullary cancer and the administration of neoadjuvant therapy in resectable PC depends on individual clinical judgment. Therefore, systematic and prospective clinical trials are essential to standardize treatment protocol in resectable PC and periampullary Cancer. This randomized controlled trial compares neoadjuvant chemotherapy followed by surgery versus upfront surgery for patients with clearly resectable pancreatic head cancer and periampullary cancer. The study aims to determine if neoadjuvant chemotherapy improves overall survival compared to immediate surgery followed by adjuvant chemotherapy.
Detailed description
Pancreatic cancer is the seventh highest cause of death from cancer worldwide, with only 20% of patients presenting with resectable disease. Despite potentially curative resections, 5-year survival remains at 20%. This study evaluates whether neoadjuvant chemotherapy can improve outcomes by eliminating occult metastatic disease and improving resection margins. Patients with clearly resectable pancreatic head cancer or periampullary cancer will be randomized 1:1 to either neoadjuvant chemotherapy followed by open or laparoscopic pancreaticoduodenectomy (Arm A) or upfront laparoscopic pancreaticoduodenectomy followed by adjuvant chemotherapy (Arm B). The primary endpoint is overall survival, with secondary endpoints including R0 resection rate , disease-free survival and perioperative outcomes.
Interventions
DRUGNeoadjuvant chemotherapy
Neoadjuvant chemotherapy (mFOLFIRINOX) followed by pancreaticoduodenectomy
PROCEDUREUpfront Surgery Group
Pancreaticoduodenectomy followed by adjuvant chemotherapy
Sponsors
Minia University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Two parallel groups: neoadjuvant chemotherapy followed by surgery versus upfront surgery
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed pancreatic head cancer or periampullary carcinoma(endoscopic ultrasound (EUS)-guided biopsy). * Clearly resectable disease as defined by National Comprehensive Cancer Network (NCCN) criteria on cross-sectional imaging: No involvement or abutment of the celiac artery, common hepatic artery, superior mesenteric artery, or replaced right hepatic artery . Less than 180 degree interface between tumor and vessel wall of the portal vein or superior mesenteric vein, and patent portal vein/splenic vein confluence No evidence of metastatic disease. * Eastern Cooperative Oncology Group (ECOG)=0-1 \& American Society of Anesthesiologists (ASA) score \<4. * Written informed consent. * Medical history without previous pancreatic resection or pancreatic cancer. * Adequate organ function (liver, kidney, bone marrow) (serum creatinine ≤2.0 mg/dL,reference range 0.5-1.20 mg/dL; serum albumin ≥2.5 g/dL, reference range 3.5-5.3; aspartate aminotransferase (AST) ≤95 U/L, reference range 0-38; Alanine aminotransferase (ALT) ≤102 U/L, reference range 0-41; prothrombin time ≤1.8, reference range 0-1.20; partial thromboplastin time ≤1.8, reference range 0.82-1.25; leukocyte count greater than 3.5×109/L, reference range 4.2-9.0; platelet count greater than 100×109/L, reference range 130-400; hemoglobin ≥9 g/dL, reference range 12-16).
Exclusion criteria
* Borderline resectable or locally advanced pancreatic or periampullary cancer. * Tumor at the body or tail of the pancreas. * Distant metastases. * Prior chemotherapy , surgery or radiotherapy for pancreatic cancer. * Severe comorbidities precluding surgery or chemotherapy. * Pregnancy or lactation. * Other neoplastic diseases (malignant)diagnosed in the past 5 years. * Major surgery or traumatic event in the past 28 days.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival rate | Up to 3 years. | Overall survival will be measured as the time between date of randomization and date of death from any cause or date of last follow-up if alive. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free survival (DFS) | Up to 3 years post-procedure. | Disease-free survival will be measured as the time between date of surgery and date of disease recurrence |
| Local recurrence rate | Up to 3 years post-procedure. | Local recurrence is defined as recurrence in the pancreatic resection margin, residual pancreas, and regional lymph nodes.The local recurrence is defined as the percentage of patients who had recurrence after the surgical resection. |
| Recurrence rate | Up to 3 years post-procedure. | The proportion of patients who experienced recurrence within 3 years from the date of surgery. |
| Time to locoregional recurrence (TLR) | Up to 3 years post-procedure. | Time to locoregional recurrence (TLR) is defined as the time from date of surgery to the date of locoregional recurrence after resection. |
| Response rate in neoadjuvant setting | 12 to 16 weeks. | Defined as the percentage of patients who showed complete response, partial response, and stable disease after the scheduled neoadjuvant chemotherapy. The evaluation is based on RECIST v.1.1. |
| Time to distant metastases (TDM) | Time between randomization and metastases prior to surgery, metastases detected during surgery, or distant recurrence after resection, assessed up to 3 years. | Time to distant metastases (TDM) is defined as the time from randomization to the date of metastases prior to surgery, metastases detected during surgery, or distant recurrence after resection. |
| Resection rate | At time of surgery or planned time of surgery. | Referred to the proportion of patients who underwent curative resection |
| R0 resection rate | One to two weeks postsurgery. | The percentage of patients that underwent a microscopically margin-negative (R0) resection. The resection is considered R0 if there is no tumor within 1 mm of the margins. |
| Lymph node-negative (N0) resection rate | One to two weeks postsurgery. | The percentage of patients that underwent a resection with negative lymph nodes (N0) in the surgical specimen. |
| Pathologic complete response (pCR) rate | One to two weeks postsurgery. | The rate (percentage) of patients who achieve a pathologic complete response (pCR) confirmed by histopathologic review of the surgical specimen. |
| Biomarker Response during neoadjuvant chemotherapy . | Baseline level is measured before start of neoadjuvant chemotherapy( within 1 week) , then after neoadjuvant therapy completion( 12 to 16 weeks). | Carbohydrate antigen (CA) 19-9 levels predictive of response to neoadjuvant chemotherapy . |
| Rate of unresectability | At time of surgery or planned time of surgery. | The rate (percentage) of patients who cannot undergo surgery due to adverse events, progressive disease, death, poor performance, or patient/physician decision, are deemed unresectable before surgery, or resection was not performed during surgery. |
| Chemotherapy start rate | upto 4 months. | The percentage of patients who received at least one cycle of scheduled chemotherapy. |
| Number of chemotherapy cycles received. | up to 4 months. | The number of scheduled chemotherapy cycles that patients received. |
| Chemotherapy completion rate | up to 4 months. | The percentage of patients who completed all cycles of scheduled chemotherapy. |
| Perioperative Complications | From surgery until 90 days post-surgery | The specific postoperative complications of pancreatic surgery include postoperative pancreatic fistula, postoperative hemorrhage ,bile leak and gastroparesis. Other common postoperative complications include abdominal infection, incision nonunion and so on. |
Countries
Egypt
Contacts
CONTACTSaleh K Saleh, MD
CONTACTRabeh K Saleh, MD
PRINCIPAL_INVESTIGATORSaleh K Saleh, MD
Minia University
Outcome results
None listed