Neoadjuvant vs Upfront Surgery for Resectable Pancreatic Cancer and Periampullary Cancer

Phase 3RecruitingNCT07081360

Minia University262 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Overall survival rate

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.

Time frame: Up to 3 years.

Secondary Outcomes

Disease-free survival (DFS)

Disease-free survival will be measured as the time between date of surgery and date of disease recurrence

Time frame: Up to 3 years post-procedure.

Local recurrence rate

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.

Time frame: Up to 3 years post-procedure.

Recurrence rate

The proportion of patients who experienced recurrence within 3 years from the date of surgery.

Time frame: Up to 3 years post-procedure.

Time to locoregional recurrence (TLR)

Time to locoregional recurrence (TLR) is defined as the time from date of surgery to the date of locoregional recurrence after resection.

Time frame: Up to 3 years post-procedure.

Response rate in neoadjuvant setting

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 frame: 12 to 16 weeks.

Time to distant metastases (TDM)

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.

Time frame: Time between randomization and metastases prior to surgery, metastases detected during surgery, or distant recurrence after resection, assessed up to 3 years.

Resection rate

Referred to the proportion of patients who underwent curative resection

Time frame: At time of surgery or planned time of surgery.

R0 resection rate

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.

Time frame: One to two weeks postsurgery.

Lymph node-negative (N0) resection rate

The percentage of patients that underwent a resection with negative lymph nodes (N0) in the surgical specimen.

Time frame: One to two weeks postsurgery.

Pathologic complete response (pCR) rate

The rate (percentage) of patients who achieve a pathologic complete response (pCR) confirmed by histopathologic review of the surgical specimen.

Time frame: One to two weeks postsurgery.

Biomarker Response during neoadjuvant chemotherapy .

Carbohydrate antigen (CA) 19-9 levels predictive of response to neoadjuvant chemotherapy .

Time frame: Baseline level is measured before start of neoadjuvant chemotherapy( within 1 week) , then after neoadjuvant therapy completion( 12 to 16 weeks).

Rate of unresectability

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.

Time frame: At time of surgery or planned time of surgery.

Chemotherapy start rate

The percentage of patients who received at least one cycle of scheduled chemotherapy.

Time frame: upto 4 months.

Number of chemotherapy cycles received.

The number of scheduled chemotherapy cycles that patients received.

Time frame: up to 4 months.

Chemotherapy completion rate

The percentage of patients who completed all cycles of scheduled chemotherapy.

Time frame: up to 4 months.

Perioperative Complications

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.

Time frame: From surgery until 90 days post-surgery

Neoadjuvant vs Upfront Surgery for Resectable Pancreatic Cancer and Periampullary Cancer

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts