Clinical trial NCT05524090: PREOPANC-4 Implementation Program for Locally Advanced Pancreatic Cancer
Official title: Nationwide Implementation Program for Optimal Multidisciplinary Management and Resection of Locally Advanced Pancreatic Cancer (PREOPANC-4)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Pancreatic Cancer
Locally Advanced Pancreatic Adenocarcinoma
Pancreatic Adenocarcinoma Non-resectable
Chemotherapy Effect
Keywords: Nationwide implementation International Best-Practice
The Netherlands
International Best-Practice
Patient Selection
Patient-centered
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: UMC Utrecht
name: Erasmus Medical Center
name: Leiden University Medical Center
name: University Medical Center Groningen
name: Radboud University Medical Center
name: Maastricht University Medical Center
name: Medisch Spectrum Twente
name: Isala
name: Frisius Medisch Centrum
name: Onze Lieve Vrouwe Gasthuis
name: Amphia ziekenhuis
name: Jeroen Bosch Ziekenhuis
name: Catharina Ziekenhuis Eindhoven
name: University of Colorado, Denver
name: Heidelberg University
name: M.D. Anderson Cancer Center
name: NYU Langone Health
name: Dutch Cancer Society
name: Maag Lever Darm Stichting
name: Deltaplan Alvleesklierkanker
First posted: 2022-09-01
Enrollment: 223
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Resection rate
timeFrame: Immediately after completing the inclusion period (December 31, 2024).
measure: Overall survival (OS)
timeFrame: After completing the follow-up period (December 31, 2029)
measure: In-hospital mortality
timeFrame: Yearly assessment throughout the inclusion period
measure: In-hospital major morbidity
timeFrame: Yearly assessment throughout the inclusion period
Secondary outcomes:
measure: R0 resection rate
timeFrame: Immediately after completing the inclusion period (December 31, 2024).
measure: Quality of life
timeFrame: Measured at 3, 6, 9, 12, 18, and 24 months from diagnosis, followed by yearly measurements.
measure: Shared decision-making: patients' healthcare satisfaction
timeFrame: Measured at 3, 6, 9, 12, 18, and 24 months from diagnosis, followed by yearly measurements.
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, locatie AMC
state: Noord-Holland
Study officials:
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Marc G Besselink, MD, MSc, PhD
role: PRINCIPAL_INVESTIGATOR
References: