Investigate whether perioperative mFOLFIRINOX improves overall survival compared to adjuvant mFOLFIRINOX in resectable pancreatic cancer.
ID
Source
Brief title
Condition
- Exocrine pancreas conditions
- Gastrointestinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint is overall survival by intention to treat.
Secondary outcome
To compare between the study arms:
• Progression free survival (PFS)
• Distant metastases free survival
• Locoregional progression free survival
• Distant metastases free interval
• Locoregional progression free interval
• Chemotherapy start rate
• Number of chemotherapy cycles received
• Chemotherapy completion rate
• Dose intensity
• Staging laparoscopy rate
• Laparoscopy yield
• Surgical exploration rate
• Resection rate
• Microscopically margin-negative resection rate
• Lymph node-negative resection rate
• Adverse events
• Postoperative complications
• Quality of life
• Serum CA 19-9 and CEA response
To investigate in arm 1 only:
• Clinical response rate
• Pathologic response
Background summary
Surgical resection followed by adjuvant FOLFIRINOX (a combination of
5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) is the standard of
care for resectable pancreatic cancer in the Netherlands. However, 50% of
patients never receive chemotherapy due to postoperative complications,
clinical deterioration or early recurrence. Neoadjuvant chemotherapy (i.e.
before surgery) can identify patients with rapidly progressing disease who can
be spared futile surgery, ensure early treatment of micro-metastases, and
improve the microscopically complete resection rate.
Study objective
Investigate whether perioperative mFOLFIRINOX improves overall survival
compared to adjuvant mFOLFIRINOX in resectable pancreatic cancer.
Study design
Multicenter randomized phase III superiority trial.
Intervention
Patients in the intervention arm receive 8 cycles of neoadjuvant mFOLFIRINOX
followed by surgical resection and 4 cycles of adjuvant mFOLFIRINOX. Patients
in the comparator arm undergo surgical resection followed by 12 cycles of
adjuvant mFOLFIRINOX.
Study burden and risks
All patients undergo a CT scan of the chest and abdomen for staging and a
pathological diagnosis is obtained using endoscopic ultrasonography (EUS) with
fine needle aspiration or biopsy (FNA/FNB) or a brush of the bile duct.
Patients in the intervention arm start with 8 cycles of neoadjuvant mFOLFIRINOX
followed by curative-intent surgery. Patients who discontinue neoadjuvant
chemotherapy because of toxicity proceed to surgery. After successful
resection, patients will receive 4 cycles of adjuvant mFOLFIRINOX.
Patients in the comparator arm start with curative-intent surgery. After
resection patients receive 12 cycles of adjuvant mFOLFIRINOX.
Evaluation with CT and tumor markers is performed in the intervention arm after
4 and 8 cycles of neoadjuvant treatment and after surgery. In the comparator
arm, evaluation with CT and tumor markers is performed after surgery and after
4 and 8 cycles of adjuvant mFOLFIRINOX.
After treatment, patients will go into routine follow-up for 5 years. Follow up
includes outpatient clinic visits, CT scans, and blood collection. All patients
are asked to complete questionnaires about quality of life during follow-up.
Toxicity of the mFOLFIRINOX regimen is well described, because it is already
the standard of care in the metastatic, locally advanced, and adjuvant setting.
In two large studies no death was attributed to mFOLFIRINOX.
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Listed location countries
Age
Inclusion criteria
• Histologically or cytologically (Bethesda 5 or 6) confirmed pancreatic ductal
adenocarcinoma.
• Resectable tumor according to DPCG criteria: no arterial contact and venous
contact with the superior mesenteric vein or portal vein of 90 degrees or less
• No evidence for metastatic disease*
• WHO performance status of 0 or 1
• Ability to undergo surgery and mFOLFIRINOX chemotherapy
• Leucocytes (WBC) >= 3.0 X 109/L
• Platelets >= 100X 109/L
• Hemoglobin >= 6.0 mmol/l
• Renal function: eGFR >= 40 ml/min
• Age >= 18 years
• Written informed consent
* Lesions on chest CT that are too small to characterize are not considered
metastatic disease.
Exclusion criteria
• Prior radiotherapy, chemotherapy, or surgery for pancreatic cancer.
• Prior chemotherapy precluding mFOLFIRINOX.
• Previous malignancy (excluding non-melanoma skin cancer, pancreatic
neuroendocrine tumor (pNET) <2cm, and gastrointestinal stromal tumor (GIST)
<2cm), unless no evidence of disease and diagnosed more than 3 years before
diagnosis of pancreatic cancer, or with a life expectancy of more than 5 years
from date of inclusion.
• Pregnancy or lactation.
• Serious concomitant systemic disorders that would compromise the safety of
the patient or his/her ability to complete the study, at the discretion of the
investigator.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-005141-16-NL |
| CCMO | NL75539.078.20 |