NeoFOL-R Trial (Perioperative Versus Adjuvnat FOLFIRINOX in Resectable Pancreatic Cancer)

Efficacy of Perioperative Versus Adjuvant FOLFIRINOX in Resectable Pancreatic Cancer: an International Multicenter Randomized Controlled Trial (NeoFOL-R Trial)

Rationale: Adjuvant chemotherapy after surgery significantly improved the survival of PC patients, but there is a problem that only about 50% of patients start adjuvant chemotherapy after pancreatectomy. Neoadjuvant chemotherapy might control potential metastatic lesion which are not being detected in early diseases 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. Asians differ from Westerners not only in racial differences, but also in average size and body surface area. Accordingly, there is an urgent need for clinical studies on the dose, toxicity, dosing cycle, and efficacy of anticancer drugs that reflect actual clinical trials in Asian countries for Asians. There are still few studies worldwide that prospectively explored the efficacy of neoadjuvant chemotherapy in resectable PC 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.

Obective: To investigate whether 6 cycles of preoperative mFOLFIRINOX - surgery - 6 cycles of postoperative mFOLFIRINOX improves overall survival by intention-to-treat compared to surgery followed by 12 cycles of postoperative mFOLFIRINOX.

Study design: open-label, multicenter, randomized, phase 3 clinical trial Study population: Patients with resectable pancreatic cancer and ECOG performance 0 or 1.

Intervention:

Invervention arm : 6 cycles of neoadjuvant mFOLFIRINOX followed by surgical resection and 6 cycles of adjuvant mFOLFIRINOX Comparator arm : surgical resection followed by 12 cycles of adjuvant mFOLFIRINOX Primary endpoint: 2-year overall survival rate by intention-to-treat

Study Overview

• Status: Recruiting
• Conditions: Resectable Pancreatic Cancer; Effects of Chemotherapy; Neoadjuvant Chemotherapy
• Intervention / Treatment: Drug: Folfirinox

• Study Type: Interventional
• Enrollment (Estimated): 609
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jin-Young Jang; Phone Number: +82-2-2072-2194; Email: jyjang4@snu.ac.kr
• Study Contact Backup: Name: Myung-Ah Lee; Email: angelamd@catholic.ac.kr

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
    • Recruiting
    • Department of Surgery, Seoul National University College of Medicine
    • Contact: Jin- Young Jang, M.D., PhD.; Phone Number: 82-2-2072-2194; Email: jangjy4@gmail.com
    • Contact: Wooil Kwon, M.D., PhD.; Phone Number: 82-2-2072-2817; Email: willdoc78@gmail.com
    • Contact: Jin- Young Jang, M.D., PhD.
    • Contact: Wooil Kwon, M.D., PhD.
  • Seoul, Korea, Republic of, 06591
    • Recruiting
    • Department of Internal Medicine, Seoul St. Mary's Hospital, Catholic University College of Medicine
    • Contact: Myung-Ah Lee, M.D., Ph.D.; Phone Number: +82-3210-3125; Email: angelamd@gatholic.ac.kr
    • Contact: Myung-Ah Lee, M.D., Ph.D.
    • Contact: Se Jun Park, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

- A. Age: 19 to 80 years old B. Patients with a score of 0 - 1 (ECOG) when selecting a study subject C. Pancreatic ductal adenocarcinoma diagnosed by histological examination (histologic or cytopathological) D. Patients evaluated as resectable pancreatic cancer in preoperative imaging as follows (NCCN guidelines for pancreatic adenocarcinoma version 2.2021)

• No arterial tumor contact (celiac asix, superior mesenteric artery, or common hepatic artery).
• No tumor contact with the superior mesenteric vein or portal vein or ≤ 180°contact without vein contour irregularity.

E. No distant metastases on preoperative imaging F. Patients with adequate organ function

1. Bone marrow function: WBC 3,000/mm3 or more or ANC 1,500/mm3 or more, platelet ≥ 100K/mm3
2. Liver function: Bilirubin ≤ 3 x upper normal limit (≤5.0 mg/dL), AST/ALT ≤ 5 x upper normal limit (<200 IU/L)
3. Renal function (Cr clearance ≥ 60 mL/min) or (Cr < 1.5 x upper normal limit) G. Persons physically capable of undergoing surgery H. Those who consented to the clinical trial I. Women of childbearing potential must have a negative serum pregnancy test within one week before starting the intervention drug. Men and women of childbearing potential must use effective contraception from screening through six months after the last dose.

Exclusion Criteria:

- Patients who met any of the following criteria are not eligible to participate in this study.

A. Those evaluated as borderline resectable or locally advanced pancreatic cancer in preoperative imaging examination (The resectability assessment depends on the presence of major vessel invasion, while invasion of adjacent organs is excluded from the criteria) B. Patients with a history of previous pancreatic surgery C. Patients with a history of previous chemotherapy or radiation therapy for pancreatic cancer D. Patients with distant metastases or recurrent pancreatic cancer E. Pancreatic body or tail cancer requiring combined resection of adjacent organs (stomach or kidney) (except for the adrenal gland) F. Patients within five years of diagnosis of other organ malignancies (with the exception of adequately treated non-melanoma skin cancer and carcinoma in situ without evidence of disease) G. Pregnant and lactating women H. Serious concomitant systemic disorders, including active or ongoing systemic infections, symptomatic congestive heart failure, unstable angina, clinically significant cardiac arrhythmias, psychiatric disorders, or uncontrolled comorbid conditions that may limit compliance with study requirements, or any medical condition that, at the discretion of the investigator, could compromise patient safety, interfere with the assessment of safety and efficacy, or hinder participation in the clinical trial.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neoadjuvant FOLFIRINOX; 6 cycles of neoadjuvant mFOLFIRINOX followed by surgical resection and 6 cycles of adjuvant mFOLFIRINOX	Drug: Folfirinox; The primary aim of this trial was to investigate whether six cycles of preoperative mFOLFIRINOX followed by six cycles of postoperative mFOLFIRINOX improved the overall survival rate by intention-to-treat compared to surgery followed by 12 cycles of postoperative mFOLFIRINOX.
Active Comparator: Upfront Surgery; surgical resection followed by 12 cycles of adjuvant mFOLFIRINOX	Drug: Folfirinox; The primary aim of this trial was to investigate whether six cycles of preoperative mFOLFIRINOX followed by six cycles of postoperative mFOLFIRINOX improved the overall survival rate by intention-to-treat compared to surgery followed by 12 cycles of postoperative mFOLFIRINOX.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-year survival rate	The primary objective of this trial is to investigate whether 6 cycles of preoperative mFOLFIRINOX - surgery - 6 cycles of postoperative mFOLFIRINOX improves overall survival by intention-to-treat compared to surgery followed by 12 cycles of postoperative mFOLFIRINOX.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Defined as the time from the date of randomization to the date of death from any cause. Patients who were not reported dead at the time of analysis were censored on the last day they were known to be alive.	5 years
Resection rate	Referred to the proportion of patients who underwent curative resection	3 years
R0 resection rate	Referred to the proportion of patients with microscopically negative resection margins due to the pathological examinations after the surgery. In this case, R0 indicated that no tumor was observed within 0 mm from the margins of resection.	3 years
Disease free survival	Defined as the time between the date of randomization and the occurrence of distant metastases, locoregional progression, or death from any cause. Patients who were alive and free of these events at the last follow-up would be censored.	3 years
Response rate in neoadjuvant setting	Defined as the percentage of patients who showed complete response, partial response, and stable disease after three or six cycles of scheduled chemotherapy. The evaluation is based on RECIST v.1.1.	3 years
Local recurrence rate	Local recurrence is defined as recurrence in the pancreatic resection margin, residual pancreas, and regional lymph nodes, and distant metastasis is defined as recurrence in a distant organ. The local recurrence and distant metastasis rates are defined as the percentage of patients who had recurrence after the surgical resection.	3 years
Recurrence rate	The proportion of patients who experienced recurrence within two years from the date of surgery.	2 year

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Collaborators: Seoul St. Mary's Hospital; Seoul National University Bundang Hospital; SMG-SNU Boramae Medical Center; Gangnam Severance Hospital
• Investigators: Study Director: Wooil Kwon, Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2023
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: September 2, 2022
• First Submitted That Met QC Criteria: September 2, 2022
• First Posted (Actual): September 7, 2022

Study Record Updates

• Last Update Posted (Estimated): November 27, 2024
• Last Update Submitted That Met QC Criteria: November 25, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Antineoplastic Agents; Folfirinox
• Other Study ID Numbers: H-2211-115-1380

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