Neoadjuvant vs Upfront Surgery for Resectable Pancreatic Cancer and Periampullary Cancer

August 24, 2025 updated by: Saleh Khairy Saleh MD, Minia University

Neoadjuvant Chemotherapy Followed by Surgery Versus Upfront Surgery for Clearly Resectable Pancreatic Head Cancer and Periampullary Cancer: A Randomized Controlled Trial

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

262

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Egypt
    • Minya Governorate
      • Minya, Minya Governorate, Egypt, 61519
        • Recruiting
        • Liver and GIT hospital , Minia University
        • Contact:
        • Sub-Investigator:
          • Sara T Boshra, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Neoadjuvant chemotherapy group (mFOLFIRINOX)
Neoadjuvant chemotherapy(mFOLFIRINOX) followed by pancreaticoduodenectomy
Drug: Neoadjuvant chemotherapy
Neoadjuvant chemotherapy (mFOLFIRINOX) followed by pancreaticoduodenectomy
Active Comparator: Upfront Surgery Group
Pancreaticoduodenectomy followed by adjuvant chemotherapy
Procedure: Upfront Surgery Group
Pancreaticoduodenectomy followed by adjuvant chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival rate
Time Frame: 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.
Up to 3 years.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of unresectability
Time Frame: 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.
At time of surgery or planned time of surgery.
Perioperative Complications
Time Frame: 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.
From surgery until 90 days post-surgery
Disease-free survival (DFS)
Time Frame: Up to 3 years post-procedure.
Disease-free survival will be measured as the time between date of surgery and date of disease recurrence
Up to 3 years post-procedure.
Local recurrence rate
Time Frame: 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.
Up to 3 years post-procedure.
Recurrence rate
Time Frame: Up to 3 years post-procedure.
The proportion of patients who experienced recurrence within 3 years from the date of surgery.
Up to 3 years post-procedure.
Time to locoregional recurrence (TLR)
Time Frame: 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.
Up to 3 years post-procedure.
Response rate in neoadjuvant setting
Time Frame: 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.
12 to 16 weeks.
Time to distant metastases (TDM)
Time Frame: 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.
Time between randomization and metastases prior to surgery, metastases detected during surgery, or distant recurrence after resection, assessed up to 3 years.
Resection rate
Time Frame: At time of surgery or planned time of surgery.
Referred to the proportion of patients who underwent curative resection
At time of surgery or planned time of surgery.
R0 resection rate
Time Frame: 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.
One to two weeks postsurgery.
Lymph node-negative (N0) resection rate
Time Frame: One to two weeks postsurgery.
The percentage of patients that underwent a resection with negative lymph nodes (N0) in the surgical specimen.
One to two weeks postsurgery.
Pathologic complete response (pCR) rate
Time Frame: 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.
One to two weeks postsurgery.
Biomarker Response during 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).
Carbohydrate antigen (CA) 19-9 levels predictive of response to neoadjuvant chemotherapy .
Baseline level is measured before start of neoadjuvant chemotherapy( within 1 week) , then after neoadjuvant therapy completion( 12 to 16 weeks).
Chemotherapy start rate
Time Frame: upto 4 months.
The percentage of patients who received at least one cycle of scheduled chemotherapy.
upto 4 months.
Number of chemotherapy cycles received.
Time Frame: up to 4 months.
The number of scheduled chemotherapy cycles that patients received.
up to 4 months.
Chemotherapy completion rate
Time Frame: up to 4 months.
The percentage of patients who completed all cycles of scheduled chemotherapy.
up to 4 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Minia University

Investigators

  • Principal Investigator: Saleh K Saleh, MD, Minia University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 20, 2025

Primary Completion (Estimated)

July 20, 2028

Study Completion (Estimated)

August 20, 2028

Study Registration Dates

First Submitted

July 4, 2025

First Submitted That Met QC Criteria

July 22, 2025

First Posted (Actual)

July 23, 2025

Study Record Updates

Last Update Posted (Estimated)

August 29, 2025

Last Update Submitted That Met QC Criteria

August 24, 2025

Last Verified

August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1563/06/2025

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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