Laparoscopic Versus Open Pancreatoduodenectomy Following Neoadjuvant Chemotherapy for BRPC

Borderline Resectable Pancreatic Cancer Clinical Trial

Official title:

Laparoscopic Versus Open Pancreatoduodenectomy Following Neoadjuvant Chemotherapy for Borderline Resectable Pancreatic Cancer: An Multicenter Open-label Randomized Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04855331
• Other study ID #: CSPAC-5
• Status: Recruiting
• Phase: N/A
• Start date: April 15, 2021
• Est. completion date: December 2025

Study information

• Verified date: May 2023
• Source: Fudan University
• Contact: Xianjun Yu, MD, PhD
• Phone: +86-13801669875
• Email: yuxianjun[@]fudanpci.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: December 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Borderline Resectable Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Procedure:
• Laparoscopic pancreatoduodenectomy
Laparoscopic pancreatoduodenectomy following neoadjuvant chemotherapy for borderline resectable pancreatic cancer.
• Open pancreatoduodenectomy
Open pancreatoduodenectomy following neoadjuvant chemotherapy for borderline resectable pancreatic cancer.

Locations

Country	Name	City	State
China	Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center	Shanghai	Shanghai

Sponsors (7)

Lead Sponsor	Collaborator
Fudan University	Fujian Provincial Hospital, Qilu Hospital of Shandong University, The Third Affiliated Hospital of Soochow University, Tongji Hospital, West China Hospital, Zhejiang Provincial People's Hospital

Country where clinical trial is conducted

China, 

References & Publications (13)

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Jang JY, Han Y, Lee H, Kim SW, Kwon W, Lee KH, Oh DY, Chie EK, Lee JM, Heo JS, Park JO, Lim DH, Kim SH, Park SJ, Lee WJ, Koh YH, Park JS, Yoon DS, Lee IJ, Choi SH. Oncological Benefits of Neoadjuvant Chemoradiation With Gemcitabine Versus Upfront Surgery in Patients With Borderline Resectable Pancreatic Cancer: A Prospective, Randomized, Open-label, Multicenter Phase 2/3 Trial. Ann Surg. 2018 Aug;268(2):215-222. doi: 10.1097/SLA.0000000000002705. — View Citation

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Reni M, Balzano G, Zanon S, Zerbi A, Rimassa L, Castoldi R, Pinelli D, Mosconi S, Doglioni C, Chiaravalli M, Pircher C, Arcidiacono PG, Torri V, Maggiora P, Ceraulo D, Falconi M, Gianni L. Safety and efficacy of preoperative or postoperative chemotherapy for resectable pancreatic adenocarcinoma (PACT-15): a randomised, open-label, phase 2-3 trial. Lancet Gastroenterol Hepatol. 2018 Jun;3(6):413-423. doi: 10.1016/S2468-1253(18)30081-5. Epub 2018 Apr 4. — View Citation

Roland CL, Yang AD, Katz MH, Chatterjee D, Wang H, Lin H, Vauthey JN, Pisters PW, Varadhachary GR, Wolff RA, Crane CH, Lee JE, Fleming JB. Neoadjuvant therapy is associated with a reduced lymph node ratio in patients with potentially resectable pancreatic cancer. Ann Surg Oncol. 2015 Apr;22(4):1168-75. doi: 10.1245/s10434-014-4192-6. Epub 2014 Oct 29. — View Citation

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Versteijne E, Suker M, Groothuis K, Akkermans-Vogelaar JM, Besselink MG, Bonsing BA, Buijsen J, Busch OR, Creemers GM, van Dam RM, Eskens FALM, Festen S, de Groot JWB, Groot Koerkamp B, de Hingh IH, Homs MYV, van Hooft JE, Kerver ED, Luelmo SAC, Neelis KJ, Nuyttens J, Paardekooper GMRM, Patijn GA, van der Sangen MJC, de Vos-Geelen J, Wilmink JW, Zwinderman AH, Punt CJ, van Eijck CH, van Tienhoven G; Dutch Pancreatic Cancer Group. Preoperative Chemoradiotherapy Versus Immediate Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Results of the Dutch Randomized Phase III PREOPANC Trial. J Clin Oncol. 2020 Jun 1;38(16):1763-1773. doi: 10.1200/JCO.19.02274. Epub 2020 Feb 27. — View Citation

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* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Recurrence free survival	The time from surgery until tumor recurrence, death or the last follow-up time.	up to 5 years after the surgery
Other	Overall survival	The time from surgery until death or the last follow-up time.	up to 5 years after the surgery
Other	Postoperative quality of life	Postoperative quality of life was assessed by the European Organization for Research and Treatment of Cancer (EORTC) quality of life scale QLQ-C30 and pancreatic cancer quality of life specific scale QLQ-PAN26.	up to 5 years after the surgery
Primary	Postoperative complications	The specific postoperative complications of pancreatic surgery include postoperative pancreatic fistula, postoperative hemorrhage and gastroparesis. Other common postoperative complications include abdominal infection, incision nonunion and so on. The degree of complications was evaluated by Clavien-Dindo grading system.	90 days after the surgery
Secondary	Length of stay	The length of hospital stay from the end of surgery to discharge or death. The length of hospital stay for readmission after discharge is not included.	90 days after the surgery
Secondary	Operation time	The time from the beginning to the end of the surgery.	1 day
Secondary	R0 resection rate	Postoperative pathology confirmed that there were no tumor cells in the tissue within 1 mm from the surgical margin.	30 days after the surgery
Secondary	The 90 days readmission rate	The rate of rehospitalization within 90 days after surgery due to aggravation.	90 days after the surgery
Secondary	The 90 days mortality rate after operation	The mortality within 90 days after surgery.	90 days after the surgery