A New Clinical Pathway for Personalized Management of Borderline Resectable and Locally Advanced Pancreatic Cancer (NORPACT-3)

A New Clinical Pathway for Personalized Management of Borderline Resectable and Locally Advanced Pancreatic Cancer - Norwegian Pancreatic Cancer Trial-3 (NORPACT 3)

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%).

Study Overview

• Status: Recruiting
• Conditions: Chemotherapy Effect; Pancreatectomy; Borderline Resectable Pancreatic Cancer; Locally Advanced Pancreatic Cancer
• Intervention / Treatment: Drug: Chemotherapy; Diagnostic test: Radiology; Procedure: Pancreatectomy; Procedure: Endoscopy

• Study Type: Observational
• Enrollment (Estimated): 400

Contacts and Locations

• Study Contact: Name: Knut Jørgen Labori, MD PhD; Phone Number: +4723070000; Email: uxknab@ous-hf.no
• Study Contact Backup: Name: Jacob Ghotbi, MD; Phone Number: +4723070000; Email: Jacob.Ghotbi@ous-hf.no

Study Locations

• Norway
  • Bergen, Norway, 5021
    • Not yet recruiting
    • Haukeland University Hospital
    • Contact: Jon-Helge Angelsen, MD PhD; Phone Number: +47 55 97 50 00; Email: jon-helge.angelsen@helse-bergen.no
  • Oslo, Norway, 0424
    • Recruiting
    • Oslo University Hospital
    • Contact: Jacob Ghotbi, MD; Phone Number: +4723070000; Email: Jacob.Ghotbi@ous-hf.no
    • Contact: Knut J Labori, MD PhD; Phone Number: +4723070000; Email: uxknab@ous-hf.no
  • Stavanger, Norway, 4068
    • Not yet recruiting
    • Stavanger University Hospital
    • Contact: Kjetil Søreide, MD PhD; Phone Number: +47 51 51 80 00; Email: kjetil.soreide@uib.no
  • Tromsø, Norway, 9038
    • Not yet recruiting
    • University Hospital of North Norway
    • Contact: Linn S Nymo, MD PhD; Phone Number: +47 77 62 60 00; Email: Linn.Save.Nymo@unn.no
  • Trondheim, Norway, 7006
    • Not yet recruiting
    • St. Olavs Hospital, Trondheim University Hospital
    • Contact: Erling A Bringeland, MD PhD; Phone Number: +47 72 57 30 00; Email: Erling.Audun.Bringeland@stolav.no

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Nationwide, population based cohort from a universal health care system

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resection rate (of the pancreatic tumour)	Resection rate: National target of 50% in BRPC and 15% in LAPC in patients initiating primary chemotherapy.	From November 2024-December 2027

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	After resection, median overall survival of 24 months, 1 year survival 80%, and 5 year survival >20%.	From November 2024-December 2027
Mortality after surgical resection	90-day postoperative mortality ≤5%	From November 2024-December 2027
Morbidity after surgical resection	90-day postoperative major morbidity (Clavien-Dindo ≥ grade3) of ≤40%	From November 2024-December 2027
Number of patients evaluated at national MDT undergoing resection		From November 2024-December 2027
Adverse events	Adverse events during primary chemotherapy	From November 2023-December 2027
R0 resection rate	R0 (microscopic radical resection >1mm) versus R1 (microscopic residual tumor ≤1mm).	From November 2023-December 2027
Quality of life EORTC QLQ-C30	Outcome measures will be calculated, according to the validated questionnaire manuals.	Measured at baseline, 3, 6, and 12 months from diagnosis, followed by yearly measurements.]
Quality of life EORTC QLQ-PAN26	Outcome measures will be calculated, according to the validated questionnaire manuals.	Measured at baseline, 3, 6, and 12 months from diagnosis, followed by yearly measurements.
Quality of life EQ-5D-5L	Outcome measures will be calculated, according to the validated questionnaire manuals.	Measured at baseline, 3, 6, and 12 months from diagnosis, followed by yearly measurements.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
PET CT	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	From November 2023-December 2027
Molecular profiling (KRAS mutation status, MSI) at time of diagnosis	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.	From November 2023-December 2027

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Collaborators: University Hospital of North Norway; Helse Stavanger HF; Haukeland University Hospital; St.Olavs Hospital, Trondheim University Hospital, Norway

Publications and helpful links

General Publications

• Springfeld C, Ferrone CR, Katz MHG, Philip PA, Hong TS, Hackert T, Buchler MW, Neoptolemos J. Neoadjuvant therapy for pancreatic cancer. Nat Rev Clin Oncol. 2023 May;20(5):318-337. doi: 10.1038/s41571-023-00746-1. Epub 2023 Mar 17.
• Farnes I, Kleive D, Verbeke CS, Aabakken L, Issa-Epe A, Smastuen MC, Fosby BV, Dueland S, Line PD, Labori KJ. Resection rates and intention-to-treat outcomes in borderline and locally advanced pancreatic cancer: real-world data from a population-based, prospective cohort study (NORPACT-2). BJS Open. 2023 Nov 1;7(6):zrad137. doi: 10.1093/bjsopen/zrad137.
• Boggi U, Kauffmann EF, Napoli N, Barreto SG, Besselink MG, Fusai GK, Hackert T, Hilal MA, Marchegiani G, Salvia R, Shrikhande SV, Truty M, Werner J, Wolfgang C, Bannone E, Capretti G, Cattelani A, Coppola A, Cucchetti A, De Sio D, Di Dato A, Di Meo G, Fiorillo C, Gianfaldoni C, Ginesini M, Hidalgo Salinas C, Lai Q, Miccoli M, Montorsi R, Pagnanelli M, Poli A, Ricci C, Sucameli F, Tamburrino D, Viti V, Cameron J, Clavien PA, Asbun HJ; REDISCOVER guidelines group. REDISCOVER guidelines for borderline-resectable and locally advanced pancreatic cancer: management algorithm, unanswered questions, and future perspectives. Updates Surg. 2024 Sep;76(5):1573-1591. doi: 10.1007/s13304-024-01860-0. Epub 2024 Apr 29.
• Stoop TF, Theijse RT, Seelen LWF, Groot Koerkamp B, van Eijck CHJ, Wolfgang CL, van Tienhoven G, van Santvoort HC, Molenaar IQ, Wilmink JW, Del Chiaro M, Katz MHG, Hackert T, Besselink MG; International Collaborative Group on Locally Advanced Pancreatic Cancer. Preoperative chemotherapy, radiotherapy and surgical decision-making in patients with borderline resectable and locally advanced pancreatic cancer. Nat Rev Gastroenterol Hepatol. 2024 Feb;21(2):101-124. doi: 10.1038/s41575-023-00856-2. Epub 2023 Nov 30.

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2024
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: January 17, 2025
• First Submitted That Met QC Criteria: April 17, 2025
• First Posted (Actual): April 25, 2025

Study Record Updates

• Last Update Posted (Actual): April 25, 2025
• Last Update Submitted That Met QC Criteria: April 17, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Pancreatectomy; Locally Advanced Pancreatic Cancer; ctDNA; FDG PET-CT; Borderline Resectable Pancreatic Cancer; Resection rate; Chemotherapy Effect; Primary chemotherapy
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Fluorodeoxyglucose F18
• Other Study ID Numbers: REK sør-øst D 733339; 2023010 (Other Grant/Funding Number: Southern and Eastern Norway Regional Health Authority); 279530-2023 (Other Grant/Funding Number: Norwegian Cancer Society)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No