Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000005550
Ethics application status
Approved
Date submitted
23/11/2023
Date registered
8/01/2024
Date last updated
11/08/2024
Date data sharing statement initially provided
8/01/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Neoadjuvant chemotherapy in resectable pancreatic cancer
Scientific title
Efficacy of Neoadjuvant FOLFIRINOX in Resectable pancreatic cancer: An international multicenter prospective randomized, controlled trial (NeoFOL-R)
Secondary ID [1] 311017 0
Nil known
Universal Trial Number (UTN)
Trial acronym
NeoFOL-R
Linked study record
This record describes the Australian-specific protocol and recruitment sites for a multi-site international trial that has been registered with the Clinical Research Information Service (CRiS) of Republic of Korea - KCT0008360 and ClinicalTrials.gov - NCT05529940.

Health condition
Health condition(s) or problem(s) studied:
Pancreatic cancer 332136 0
Condition category
Condition code
Cancer 328858 328858 0 0
Pancreatic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This clinical trial will consist of:

- 12 cycles of mFOLFIRINOX maintenance chemotherapy after surgery (Arm A) and
- 6 cycles of mFOLFIRINOX chemotherapy followed by surgery and 6 cycles of postoperative mFOLFIRINOX chemotherapy (Arm B)

for patients with histologically diagnosed resectable pancreatic ductal adenocarcinoma.

Both arms will receive a total of 12 chemotherapy cycles administered over 24 weeks (i.e., 14 days per cycle).

Arm A will start mFOLFIRINOX within 8 weeks after surgery. Arm B will have surgery 4-6 weeks after completion of mFOLFIRINOX, and start post-operative mFOLFIRINOX within 8 weeks after surgery.

The recruitment goal will be 100 participants in Australia. The 100 participants will be assigned to the neoadjuvant chemotherapy group and the upfront surgery group in a 1:1 ratio; thus, the number of patients in each group will be 50 (neoadjuvant chemotherapy group) and 50 (upfront surgery group), respectively.

Route of administration and dosage of mFOLFIRINOX:
Oxaliplatin (85 mg/m2) is initially administered intravenously for 2 h, after which 50 mg/m2 leucovorin is injected over 2 h, and irinotecan (180 mg/m2) is administered for 90 min intravenously at the same time. Subsequently, a single intravenous infusion of 5-Fluorouracil (5-FU; 400 mg/m2) is administered. After that, 2400 mg/m2 of 5-FU is injected intravenously for 44 h. This process is repeated every 2 weeks.
* Irinotecan is dose-adjustable from 150-180 mg/m2 depending on patient condition.

Chemotherapy will be administered on the planned visit date, but it can be administered ± 2 days from the scheduled visit date. Primary prophylaxis with granulocyte-colony stimulating factor (G-CSF) is recommended after every cycle of mFOLFIRINOX. The recommended dose of G-CSF (for the prevention of febrile neutropenia is 5 micrograms/kg/day, commencing the day after chemotherapy and finishing after 10-14 days, when the post-nadir neutrophil level has reached 10x 10^9/L.

Dose adjustments during treatment will be based on the maximum graded toxicity within the previous cycle, using the Common Terminology Criteria for Adverse Events (CTCAE ver 5.0) and as per the treating clinician’s discretion.

Surgery:
The type of surgery performed will vary depending on the location of the lesion. Pancreaticoduodenectomy is to be performed if the lesion is located in the pancreatic head, and distal pancreatectomy will be performed if the lesion is located in the body or tail of the pancreas. Splenectomy will be performed during distal pancreatectomy.
Intervention code [1] 327464 0
Treatment: Surgery
Intervention code [2] 327465 0
Treatment: Drugs
Comparator / control treatment
The comparator / control group will include individuals with histologically diagnosed resectable pancreatic ductal adenocarcinoma, who will be treated with 12 cycles of mFOLFIRINOX maintenance chemotherapy after surgery (Arm A).

Arm A will start mFOLFIRINOX within 8 weeks after surgery. A
Control group
Active

Outcomes
Primary outcome [1] 336660 0
Change in overall survival rate between individuals who receive mFOLFIRINOX before and after surgery, compared to those who only receive postoperative mFOLFIRINOX.
Assessment method [1] 336660 0
Survival data will be collected from review of medical records.
Timepoint [1] 336660 0
The first follow-up visit will commence immediately after the completion of therapy, They will subsequently be performed every 4 months after the first day of the last postoperative chemotherapy cycle.
Secondary outcome [1] 429642 0
Resection rate
Assessment method [1] 429642 0
Resection rate: Referred to the proportion of patients who underwent curative resection. These data will be collected from medical records.
Timepoint [1] 429642 0
The first follow-up visit will commence immediately after the completion of therapy, They will subsequently be performed every 4 months after the first day of the last postoperative chemotherapy cycle.
Secondary outcome [2] 429643 0
Disease-free survival
Assessment method [2] 429643 0
Disease-free survival: Defined as the time between the date of operation and the occurrence of distant metastases, locoregional progression, or death from any cause. Patients who alive and free of these events at the last follow-up will be censored. These data will be collected from medical records.
Timepoint [2] 429643 0
The first follow-up visit will commence immediately after the completion of therapy, They will subsequently be performed every 4 months after the first day of the last postoperative chemotherapy cycle.
Secondary outcome [3] 429644 0
R0 resection rate
Assessment method [3] 429644 0
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 indicates that no tumour is observed within 0 mm from the margins of resection. These data will be collected from medical records.
Timepoint [3] 429644 0
The first follow-up visit will commence immediately after the completion of therapy, They will subsequently be performed every 4 months after the first day of the last postoperative chemotherapy cycle.
Secondary outcome [4] 429646 0
Lymph node negativity resection rate
Assessment method [4] 429646 0
Lymph node-negative resection rate: Defined as the percentage of patients who underwent resection with negative lymph nodes (N0) in the surgical specimen. These data will be collected from medical records.
Timepoint [4] 429646 0
The first follow-up visit will commence immediately after the completion of therapy, They will subsequently be performed every 4 months after the first day of the last postoperative chemotherapy cycle.
Secondary outcome [5] 429647 0
Local recurrence rate
Assessment method [5] 429647 0
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. Local recurrence and distant metastasis rates are defined as the percentage of patients who have recurrence after the surgical resection. These data will be collected from medical records.
Timepoint [5] 429647 0
The first follow-up visit will commence immediately after the completion of therapy, They will subsequently be performed every 4 months after the first day of the last postoperative chemotherapy cycle.
Secondary outcome [6] 429648 0
Response rate after preoperative chemotherapy
Assessment method [6] 429648 0
Response rate after preoperative chemotherapy: 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 via CT scans. These data will be collected from medical records.
Timepoint [6] 429648 0
The first follow-up visit will commence immediately after the completion of therapy, They will subsequently be performed every 4 months after the first day of the last postoperative chemotherapy cycle.
Secondary outcome [7] 429649 0
Adverse events, defined according to CTCAE version 5.0.
Assessment method [7] 429649 0
These data will be collected from medical records.
Timepoint [7] 429649 0
The first follow-up visit will commence immediately after the completion of therapy, They will subsequently be performed every 4 months after the first day of the last postoperative chemotherapy cycle.

Eligibility
Key inclusion criteria
Patients must meet all of the following criteria to participate in this study.
1. Age: 18 – 80 years
2. Patients with an Eastern Cooperative Oncology Group (ECOG) score of 0 – 2
3. Pancreatic ductal adenocarcinoma diagnosed by histological examination (histologic or cytopathological)
4. Patients evaluated for resectable pancreatic cancer on preoperative imaging as follows (NCCN guidelines for pancreatic adenocarcinoma version 2.2021)
a. There is no arterial tumour contact (celiac artery, superior mesenteric artery, or common hepatic artery).
b. There is no tumour contact with the superior mesenteric vein or portal vein or equal to or less than 180°contact without vein contour irregularity.
5. No distant metastases on preoperative imaging
6. Patients with adequate organ function
a) Bone marrow function: WBC greater or equal to 3,000/mm3 or absolute neutrophil count (ANC) greater or equal to 1,500/mm3, platelet greater or equal to 100 K/mm3
b) Liver function: bilirubin equal or less than 3 × the upper normal limit (equal to or less than 5.0 mg/dL), AST/ALT equal to or less than 5 the upper normal limit (less than 200 IU/L)
c) Renal function (Creatinine clearance (Cr) equal to or greater than 60 mL/min) or (Cr < 1.5 x upper normal limit)
7. Persons physically capable of undergoing surgery
8. Those who consented to the clinical trial
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients who meet any of the following criteria are not eligible to participate in this study.
1) Those evaluated as borderline resectable or locally advanced pancreatic cancer in preoperative imaging examination
2) Patients with a history of previous pancreatic surgery
3) Patients with a history of previous chemotherapy or radiation therapy for pancreatic cancer
4) Patients with distant metastases or recurrent pancreatic cancer
5) Pancreatic body or tail cancer requiring combined resection of adjacent organs (stomach or kidney) (except for the adrenal gland)
6) 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)
7) Pregnant and lactating women
8) 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Each researcher participating in the study will access the program, registers the assigned participant with the given ID and password, and registers the test group at the same time. Additionally, the seed number required to reproduce the created random number table, i.e., the serial number, will be recorded and stored.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The patients will be randomly assigned into two groups according to the research institution. Randomization will be conducted by creating a web-based randomization program under the supervision of the Medical Research Collaborating Center (MRCC) at Seoul National University College of Medicine.
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis
The 2-year survival rate of patients who undertake neoadjuvant chemotherapy and upfront surgery with adjuvant chemotherapy for resectable pancreatic cancer will be presented using the Kaplan-Meier method, and the p-value will be presented using the log-rank method. Survival will be summarized using median and confidence intervals.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/05/2024
Actual
22/05/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
100
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
NSW,NT,QLD,SA,VIC

Funding & Sponsors
Funding source category [1] 315280 0
Hospital
Name [1] 315280 0
Epworth HealthCare
Country [1] 315280 0
Australia
Primary sponsor type
Hospital
Name
Epworth HealthCare
Country
Australia
Secondary sponsor category [1] 317322 0
None
Name [1] 317322 0
Country [1] 317322 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314201 0
Monash Health - Monash Health Human Research Ethics Committee
Ethics committee address [1] 314201 0
Ethics committee country [1] 314201 0
Australia
Date submitted for ethics approval [1] 314201 0
25/10/2023
Approval date [1] 314201 0
08/01/2024
Ethics approval number [1] 314201 0

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 130766 0
Mr Julian Choi
Address 130766 0
Epworth Richmond, Suite 6.5 Level 6, 89 Bridge Rd Richond VIC 3121
Country 130766 0
Australia
Phone 130766 0
+61 03 9429 1002
Fax 130766 0
Email 130766 0
julianchoi@gmail.com
Contact person for public queries
Name 130767 0
Dr Ashleigh Poh
Address 130767 0
Epworth Richmond, 89 Bridge Road, Richmond VIC 3121
Country 130767 0
Australia
Phone 130767 0
+61 03 9426 8880
Fax 130767 0
Email 130767 0
eh-jreissaticentre@epworth.org
Contact person for scientific queries
Name 130768 0
Dr Ashleigh Poh
Address 130768 0
Epworth Richmond, 89 Bridge Road, Richmond VIC 3121
Country 130768 0
Australia
Phone 130768 0
+61 03 9426 8880
Fax 130768 0
Email 130768 0
eh-jreissaticentre@epworth.org

Data sharing statement
Will the study consider sharing individual participant data?
No


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.