PREOPANC-4 Implementation Program for Locally Advanced Pancreatic Cancer (PREOPANC-4)

Nationwide Implementation Program for Optimal Multidisciplinary Management and Resection of Locally Advanced Pancreatic Cancer (PREOPANC-4)

A prospective, nationwide, implementation program of the international standard of excellence for locally advanced pancreatic cancer (LAPC) care in the Netherlands (2021[7]-2030[6]), including a multidisciplinary training program by the four leading international expert centers.

The PREOPANC-4 project aims a safe and patient-centered implementation of the international standards of excellence for LAPC (surgery) in the Netherlands.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Cancer; Chemotherapy Effect; Locally Advanced Pancreatic Adenocarcinoma; Pancreatic Adenocarcinoma Non-resectable
• Intervention / Treatment: Other: Implementation - International best-practice care

Detailed Description

Rationale:

Non-metastasized locally advanced pancreatic cancer (LAPC) is diagnosed in 35% of all pancreatic cancer patients and is traditionally treated with palliative care. Recently, the multidisciplinary management of LAPC has evolved by the introduction of modern multi-agent induction chemotherapies, leading to an increased resection rate and improved outlook for five-year survival. In contrast, five-year survival after chemotherapy without surgery is virtually non-existent. In the Netherlands, the LAPC resection rate after induction chemotherapy remains low with 8% versus 25% in international centers of excellence, leading to missed opportunities for five-year survival in a selected subgroup of LAPC patients. Explanations for this large difference include the spectrum of chemotherapy use, interpretation of diagnostics, patient selection, and surgical techniques.

Objective:

A safe and patient-centered implementation of the international standards of excellence for LAPC (surgery) in the Netherlands.

Study design:

A prospective, nationwide, implementation program of the international standard of excellence for LAPC care in the Netherlands (2021[7]-2030[6]), including a multidisciplinary training program by the four leading international expert centers (i.e. University of Heidelberg, University of Colorado, NYU Langone, and MD Anderson Cancer Center). Subsequently, the three Dutch centers with the highest surgical volume and documented experience in LAPC surgery will implement this highly complex LAPC surgery in close collaboration with the other Dutch Pancreatic Cancer Group (DPCG) centers. Patients who meet the inclusion criteria will be discussed within an online (inter)national expert panel to properly select patient for surgery. In addition, the other DPCG centers can present their LAPC patients to this panel for advice about (surgical) treatment options and if these patients should be referred to the three high-volume DPCG centers for surgery. Outcomes will be compared with a historical Dutch LAPC cohort, using propensity score matching.

Study population:

Adult patients with pathology confirmed non-metastasized LAPC and non-progressive disease after at least four months of (modified) FOLFIRINOX or gemcitabine-nab-paclitaxel induction chemotherapy and fit for major surgery.

Study aim:

The primary study aim is to double the LAPC resection rate in the Netherlands from 8% to 16% with adequate survival and morbidity targets.

Primary targets:

1. Survival: After resection, mOS of 25 months, 1-year survival >90%, and 5-year survival >20%. These outcomes will be compared to the Dutch cohort of patients (2015-2020) with RECIST non-progressive LAPC after induction chemotherapy who did not undergo surgical exploration;
2. In-hospital morbidity and mortality: in-hospital/30-day mortality ≤5% and in-hospital major morbidity of <50% after resection, which will be compared with a recent Dutch cohort (2015-2020) of resected patients with borderline resectable and locally advanced pancreatic cancer after induction/neoadjuvant therapy.

Secondary targets:

1. Non-inferior radical resection (R0) rate as compared to a recent Dutch cohort (2015-2020) of resected patients with borderline resectable and locally advanced pancreatic cancer after induction/neoadjuvant therapy;
2. Non-inferior quality of life, mental and physical health status, and potential side effects on the long-term follow-up, compared to a control cohort of Dutch LAPC patients;
3. Non-inferior patients' healthcare satisfaction, compared to the Dutch historical cohort of pancreatic cancer patients.

• Study Type: Observational
• Enrollment (Anticipated): 223

Contacts and Locations

• Study Contact: Name: Thomas F Stoop, MD; Phone Number: +316 547 555 11; Email: t.f.stoop@amsterdamUMC.nl
• Study Contact Backup: Name: Marc G Besselink, MD, MSc, PhD; Phone Number: +316 16 15 83 45; Email: m.g.besselink@amsterdamUMC.nl

Study Locations

• Netherlands
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1105 AZ
      • Recruiting
      • Amsterdam UMC, Locatie AMC
      • Contact: Thomas F Stoop, MD; Phone Number: +316 547 555 11; Email: t.f.stoop@amsterdamUMC.nl
      • Contact: Marc G Besselink, MD, MSc, PhD; Email: m.g.besselink@amsterdamUMC.nl
      • Principal Investigator: Marc G Besselink, MD, PhD, MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Adult patients with pathology confirmed non-metastasized LAPC and non-progressive disease after at least two months of (modified) FOLFIRINOX or gemcitabine-nab-paclitaxel induction chemotherapy and fit for major surgery.

Description

Inclusion Criteria:

• Age 18 years or older
• Pathology-confirmed (LAPC)*
• CT-based non-progressive disease (RECIST criteria) after at least 4 months of systemic chemotherapy ([m]FOLFIRINOX / gemcitabine-nab-paclitaxel).

Exclusion Criteria:

• Metastatic pancreatic cancer prior to induction chemotherapy.

  • According to the Dutch Pancreatic Cancer Group (DPCG) definition: >90 degrees arterial tumor involvement (i.e. superior mesenteric artery, celiac axis, and/or hepatic artery) and/or portovenous involvement of either >270 degrees or occlusion.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Implementation cohort; Inclusion criteria: Age ≥18 years;; Pathology confirmed LAPC*;; CT-based non-progressive disease in accordance with the RECIST criteria after at least 4 months of systemic chemotherapy ([m]FOLFIRINOX or gemcitabine-nab-paclitaxel). Exclusion criteria: (1) Metastatic pancreatic cancer prior to induction chemotherapy. *According to the Dutch Pancreatic Cancer Group (DPCG) definition: >90 degrees arterial tumor involvement (i.e. superior mesenteric artery, celiac axis, and/or hepatic artery) and/or portovenous involvement of either >270 degrees or occlusion.

Other: Implementation - International best-practice care; The PREOPANC-4 project aims to safely implement the international standard of excellence for LAPC management and surgery using a multidisciplinary best-practice training program, based on the experiences of four leading international expert centers (i.e. NYU Langone Health, University of Colorado, Heidelberg University, and MD Anderson Cancer Center). We hypothesize that the PREOPANC-4 implementation project will result in the improvement in multidisciplinary patient management and selection in line with current international best-practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resection rate	Resection rate of the pancreatic tumor	Immediately after completing the inclusion period (December 31, 2024).
Overall survival (OS)	OS from time of resection (mOS, 1-year OS & 5-year OS)	After completing the follow-up period (December 31, 2029)
In-hospital mortality	Mortality after resection (during primary hospitalization)	Yearly assessment throughout the inclusion period
In-hospital major morbidity	Clavien-Dindo grade IIIa or higher major morbidity after resection (during primary hospitalization)	Yearly assessment throughout the inclusion period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
R0 resection rate	R0 (microscopic radical resection >1mm) versus R1 (microscopic residual tumor ≤1mm). NB. For the anterior margin, only direct ingrowth is considered as R1.	Immediately after completing the inclusion period (December 31, 2024).
Quality of life	EORTC QLQ-C30: global health status Outcome measures will be calculated, according to the validated questionnaire manuals.	Measured at 3, 6, 9, 12, 18, and 24 months from diagnosis, followed by yearly measurements.
Shared decision-making: patients' healthcare satisfaction	APECC decision-making self-efficacy scale. Outcome measures will be calculated, according to the validated questionnaire manuals.	Measured at 3, 6, 9, 12, 18, and 24 months from diagnosis, followed by yearly measurements.

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Collaborators: M.D. Anderson Cancer Center; University of Colorado, Denver; Radboud University Medical Center; NYU Langone Health; University Medical Center Groningen; Maastricht University Medical Center; UMC Utrecht; Erasmus Medical Center; Catharina Ziekenhuis Eindhoven; Heidelberg University; Leiden University Medical Center; Medical Centre Leeuwarden; Onze Lieve Vrouwe Gasthuis; Jeroen Bosch Ziekenhuis; Maag Lever Darm Stichting; Isala; Dutch Cancer Society; Medisch Spectrum Twente; Amphia ziekenhuis; Deltaplan Alvleesklierkanker
• Investigators: Principal Investigator: Marc G Besselink, MD, MSc, PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 1, 2021
• Primary Completion (ANTICIPATED): December 31, 2024
• Study Completion (ANTICIPATED): December 31, 2030

Study Registration Dates

• First Submitted: August 16, 2022
• First Submitted That Met QC Criteria: August 29, 2022
• First Posted (ACTUAL): September 1, 2022

Study Record Updates

• Last Update Posted (ACTUAL): September 1, 2022
• Last Update Submitted That Met QC Criteria: August 29, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Patient Selection; Patient-centered; The Netherlands; Nationwide implementation International Best-Practice; International Best-Practice
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Adenocarcinoma; Pancreatic Neoplasms
• Other Study ID Numbers: W21_487 # 21.541

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No