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

Neoadjuvant Chemotherapy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05529940
• Other study ID #: H-2211-115-1380
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: September 2023
• Est. completion date: December 2027

Study information

• Verified date: August 2023
• Source: Seoul National University Hospital
• Contact: Jin-Young Jang
• Phone: +82-2-2072-2194
• Email: jyjang4[@]snu.ac.kr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 609
• Est. completion date: December 2027
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 80 Years

Eligibility

Inclusion Criteria:

• A. Age: 19 to 80 years old B. Patients with a score of 0 - 2 (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

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 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 that would compromise the safety of the patient or patient's ability to complete the study at the discretion of the investigator

Related Conditions & MeSH terms

• Effects of Chemotherapy
• Neoadjuvant Chemotherapy
• Pancreatic Neoplasms
• Resectable Pancreatic Cancer

Intervention

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.

Locations

Country	Name	City	State
Korea, Republic of	Department of Internal Medicine, Seoul St. Mary's Hospital, Catholic University College of Medicine	Seoul
Korea, Republic of	Department of Surgery, Seoul National University College of Medicine	Seoul

Sponsors (5)

Lead Sponsor	Collaborator
Seoul National University Hospital	Gangnam Severance Hospital, Seoul National University Bundang Hospital, Seoul St. Mary's Hospital, SMG-SNU Boramae Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Resection rate	Referred to the proportion of patients who underwent curative resection	3 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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