Clinical trial NCT04855331: Laparoscopic Versus Open Pancreatoduodenectomy Following Neoadjuvant Chemotherapy for BRPC
Official title: Laparoscopic Versus Open Pancreatoduodenectomy Following Neoadjuvant Chemotherapy for Borderline Resectable Pancreatic Cancer: An Multicenter Open-label Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Borderline Resectable Pancreatic Cancer
Keywords: Pancreatic Ductal Adenocarcinoma
Neoadjuvant Chemotherapy
Laparoscopic Pancreatoduodenectomy
Safety and Efficacy
Lead sponsor: Fudan University
Sponsor class: OTHER
Collaborators: name: The Third Affiliated Hospital of Soochow University
name: Qilu Hospital of Shandong University
name: West China Hospital
name: Tongji Hospital
name: Fujian Provincial Hospital
name: Zhejiang Provincial People's Hospital
First posted: 2021-04-22
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this study is to evaluate the safety and efficacy of laparoscopic versus open pancreatoduodenectomy following neoadjuvant chemotherapy for borderline resectable pancreatic cancer

Detailed description: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumors with an increasing incidence and constitutes the fourth leading cause of cancer-related deaths. Radical resection remains the potential curative treatments for selected patients, and the Miami international evidence-based guidelines suggest that minimally invasive resection is feasible, safe, and oncologically equivalent for PDAC patients compared with open surgery. Furthermore, minimally invasive pancreatomy was associated with better overall and disease-free survival.

However, only 15% to 20% PDAC patients are eligible for upfront surgery at the time of initial diagnosis. For borderline resectable PDAC, studies have confirmed that neoadjuvant therapy can provide more oncological benefits than upfront surgery, such as improved rates of margin-negative resection and decreased incidence of lymph node metastases. Additionally, short-term neoadjuvant therapy has been shown to improve postoperative survival. These findings support the use of short-term neoadjuvant therapy in borderline resectable PDACs, as recommended by the National Comprehensive Cancer Network guidelines.

Neoadjuvant therapy can lead to severe fibrosis in the localized tumor tissue, which may hinder dissection and increase the risk of dangerous and bloody surgery. Furthermore, most anatomically borderline resectable PDACs have a large diameter and are in close proximity to major blood vessels, making the surgical procedure more complex and challenging. To date, there is insufficient evidence to determine the feasibility and safety of minimally invasive pancreatectomy compared to open surgery after neoadjuvant therapy.

This study aims to evaluate the safety and efficacy of laparoscopic pancreatoduodenectomy (LPD) versus open pancreatoduodenectomy (OPD) for borderline resectable PDAC following neoadjuvant chemotherapy (NACT) through a multicenter randomized controlled clinical trial.

Eligibility criteria: Inclusion Criteria:

* Before neoadjuvant chemotherapy, pancreatic ductal adenocarcinoma was confirmed by pathology;
* According to the guidelines, neoadjuvant chemotherapy should be performed before surgery, including patients with resectable pancreatic cancer (RPC) with high risk factors (biologically borderline resectable), anatomically borderline resectable pancreatic cancer (BRPC) with good physical condition;
* Receive at least 2 cycles of neoadjuvant chemotherapy before radical surgery；
* After neoadjuvant chemotherapy, the patient can be further treated by laparoscopic or open surgery;
* No obvious surgical contraindications, suitable for minimally invasive surgery;
* ECOG score of preoperative physical condition was 0-1;
* No history of preoperative pancreatitis;
* Preoperative PET-CT or other imaging examination did not show distant metastasis;
* The expected postoperative survival time was more than 3 months;
* Be able to comply with research protocol, follow-up plan and other protocol requirements;
* Voluntary participation and signed informed consent.

Exclusion Criteria:

* Neoadjuvant chemotherapy is not suitable before operation according to the guidelines;
* Invasion of adjacent organs, abdominal cavity or distant metastasis was found by introperative exploration;
* Patients requiring total pancreatectomy;
* Severe impairment of heart, liver and kidney function;
* Patients with other malignancies or hematological diseases;
* The patient is pregnant, planning to be pregnant or lactating；
* Before surgery, anti-cancer therapy except neoadjuvant chemotherapy were performed, including interventional chemoembolization, ablation, radiotherapy and molecular targeted therapy;
* Participants in other clinical trials;
* Tumor progression occurred during neoadjuvant chemotherapy. After neoadjuvant chemotherapy, patients failed reach the standard of laparoscopic surgery.

Primary outcomes:
measure: Postoperative complications
timeFrame: 90 days after the surgery
Secondary outcomes:
measure: Length of stay
timeFrame: 90 days after the surgery
measure: Operation time
timeFrame: 1 day
measure: R0 resection rate
timeFrame: 30 days after the surgery
measure: The 90 days readmission rate
timeFrame: 90 days after the surgery
measure: The 90 days mortality rate after operation
timeFrame: 90 days after the surgery
Other outcomes:
measure: Recurrence free survival
timeFrame: up to 5 years after the surgery
measure: Overall survival
timeFrame: up to 5 years after the surgery
measure: Postoperative quality of life
timeFrame: up to 5 years after the surgery
Locations:
city: Shanghai
country: China
facility: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
affiliation: Fudan University
name: Xianjun Yu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fudan University
name: Xiaowu Xu, MD
role: STUDY_DIRECTOR
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