Borderline Resectable Pancreatic Cancer, Chemotherapy Effect, Locally Advanced Pancreatic Cancer, Pancreatectomy
Conditions
Keywords
Primary chemotherapy, Resection rate, Borderline Resectable Pancreatic Cancer, Locally Advanced Pancreatic Cancer, Pancreatectomy, Chemotherapy Effect, FDG PET-CT, ctDNA
Brief summary
NORPACT-3 is a nationwide, Norwegian single arm prospective study that evaluates the resectability rates and survival in patients with borderline resectable and locally advanced pancreatic cancer who received primary chemotherapy. Eligible patients are treated with primary chemotherapy possibly followed by surgical exploration and resection. All Norwegian centres performing pancreatic surgery have agreed to collaborate in this trial. The assignment of the medical intervention is not at the discretion of the investigator, but follow the national Norwegian guidelines regarding diagnostic work up, oncological and surgical treatment and follow up. The primary aim is a national resection rate of 50% in BRPC and 15% in LAPC in patients initiating primary chemotherapy, with adequate overall survival and morbidity/mortality (after resection median overall survival of 24 months, 1 year survival 80%, and 5 year survival \>20% + 90 day postoperative mortality ≤5%, 90-day postoperative major morbidity (Clavien Dindo grade 3) ≤40%).
Interventions
DRUGChemotherapy
The choice of chemotherapy regimen follows national guidelines, preferably mFOLFIRINOX or gemcitabine-nab-paclitaxel.
DIAGNOSTIC_TESTRadiology
PET/CT is optional. PET/CT will be offered as a part of the diagnostic work up at baseline and one additional scan after a minimum of two months of chemotherapy.
PROCEDUREPancreatectomy
Surgery is scheduled within 4 weeks after the last neoadjuvant infusion. Resection will be performed as a standard or pylorus-preserving pancreatoduodenectomy (PD), distal pancreatectomy (DP) with splenectomy, or total pancreatectomy (TP) with splenectomy, and with or without venous or arterial resection and reconstruction.
PROCEDUREEndoscopy
Endoscopic ultrasound fine-needle biopsy to establish the diagnosis with histopathology and to obtain an adequate sample for molecular pathology (KRAS status (mutation or wild type), microsatellite instability (MSI)).
Sponsors
University Hospital of North Norway
Haukeland University Hospital
Helse Stavanger HF
St.Olavs Hospital, Trondheim University Hospital, Norway
Oslo University Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Borderline resectable or locally advanced adenocarcinoma of the pancreas (NCCN, version 2, 2021) (Appendix 3) * Nx, M0 (UICC 8th version, 2016) * Cytological or histological confirmation of adenocarcinoma * Age \>18 year * Considered able to receive primary chemotherapy and possible surgery * Written informed consent
Exclusion criteria
* Co-morbidity or performance status precluding primary chemotherapy * Co-morbidity or performance status precluding pancreatectomy * Female patients in child-bearing age not using adequate contraception, pregnant or lactating women * Mental or physical disorders that could interfere with treatment of with the provision of informed consent * Any reason why, in the opinion of the investigator, the patient should not participate
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Resection rate (of the pancreatic tumour) | From November 2024-December 2027 | Resection rate: National target of 50% in BRPC and 15% in LAPC in patients initiating primary chemotherapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | From November 2024-December 2027 | After resection, median overall survival of 24 months, 1 year survival 80%, and 5 year survival \>20%. |
| Mortality after surgical resection | From November 2024-December 2027 | 90-day postoperative mortality ≤5% |
| Morbidity after surgical resection | From November 2024-December 2027 | 90-day postoperative major morbidity (Clavien-Dindo ≥ grade3) of ≤40% |
| Number of patients evaluated at national MDT undergoing resection | From November 2024-December 2027 | — |
| Adverse events | From November 2023-December 2027 | Adverse events during primary chemotherapy |
| Quality of life EORTC QLQ-PAN26 | Measured at baseline, 3, 6, and 12 months from diagnosis, followed by yearly measurements. | Outcome measures will be calculated, according to the validated questionnaire manuals. |
| Quality of life EQ-5D-5L | Measured at baseline, 3, 6, and 12 months from diagnosis, followed by yearly measurements. | Outcome measures will be calculated, according to the validated questionnaire manuals. |
| R0 resection rate | From November 2023-December 2027 | R0 (microscopic radical resection \>1mm) versus R1 (microscopic residual tumor ≤1mm). |
| Quality of life EORTC QLQ-C30 | Measured at baseline, 3, 6, and 12 months from diagnosis, followed by yearly measurements.] | Outcome measures will be calculated, according to the validated questionnaire manuals. |
Other
| Measure | Time frame | Description |
|---|---|---|
| PET CT | From November 2023-December 2027 | * Extrapancreatic disease detected at baseline PET-CT * Correlation of PET-CT findings with histopathological tumor regression grading * Correlation of PET-CT findings with CA19-9 dynamics * Prognostic value of metabolic tumor response in resected patients |
| Molecular profiling (KRAS mutation status, MSI) at time of diagnosis | From November 2023-December 2027 | * Number of patients with KRAS mutations, KRAS wild type, or MSI tumors * Number of patients undergoing additional genetic profiling and/or targeted therapy in accordance with the national guidelines protocols or ongoing trials. |
Countries
Norway
Contacts
Primary ContactKnut Jørgen Labori, MD PhD
Backup ContactJacob Ghotbi, MD
Outcome results
None listed