None listed
Conditions
Brief summary
This project is investigating the use of chemotherapy drugs called mFOLFIRINOX in individuals with pancreatic cancer before surgery, rather than the usual process of using these drugs after surgery. Who is it for? You may be eligible for this study if you are aged between 18 and 80 years, you have been diagnosed with pancreatic cancer that is suitable to be treated by surgery and you meet other health requirements. Study details Participants who choose to enrol in this study will be randomly allocated by chance (similar to flipping a coin) to one of two treatment arms. Participants who are allocated to treatment arm A will undergo surgery first, followed by 12 cycles of mFOLFIRINOX chemotherapy. Participants who are allocated to treatment arm B will undergo 6 cycles of mFOLFIRINOX chemotherapy, followed by surgery and will then complete the last 6 cycles of mFOLFIRINOX. It is hoped this research will determine whether administering these chemotherapy drugs before surgery has a positive impact including possibly shrinking tumours prior to surgery. If this study finds that pre-surgical chemotherapy is beneficial, this information could be used to improve outcomes for future pancreatic cancer patients.
Interventions
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
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.
Sponsors
Epworth HealthCare
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Healthy volunteers
No
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
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
Outcome results
None listed