Recurrent Disease Detection After Resection of Pancreatic Adenocarcinoma Using a Standardized Surveillance Strategy (RADAR-PANC)

Recurrent Disease Detection After Resection of Pancreatic Adenocarcinoma Using a Standardized Surveillance Strategy: a Nationwide Randomized Controlled Trial

A randomized controlled trial, nested within an existing prospective cohort (Dutch Pancreatic Cancer Project; PACAP) and the United Kingdom (UK) Pancreas Cancer: Observations of Practice and survival; PACOPS) according to the 'trials within cohorts' (TwiCs) design in which the effect of a standardized surveillance, with serial tumor marker testing and routine imaging, compared to current non-standardized practice, on overall survival and quality of life in patients with primary resected PDAC is investigated. The most important secondary endpoint is quality of life. Other secondary endpoints are clinical and radiological patterns of PDAC recurrence, the compliance of patients to our standardized follow-up strategy, the impact of a standardized surveillance on (eligibility for) additional treatment, and the tolerance of additional treatment. The need for this clinical trial is emphasized by the the emergence of more potent local and more effective systemic treatments for PDAC recurrence, leading to a rising interest in early diagnosis by a standardized approach to follow-up with routine imaging and serial serum tumor marker testing.

Study Overview

• Status: Enrolling by invitation
• Conditions: Resectable Pancreatic Ductal Adenocarcinoma; Recurrent Pancreatic Ductal Adenocarcinoma
• Intervention / Treatment: Other: Standardized surveillance

Detailed Description

Rationale: Radical resection combined with (neo)adjuvant chemotherapy offers the best chances for long-term survival for patients with resectable localized pancreatic ductal adenocarcinoma (PDAC). However, even after radical resection, almost all patients will experience local and/or distant disease recurrence after sufficient follow-up, mostly within 2 years. There is a lack of evidence based effective therapeutic options for the significant group of patients with local recurrence only, in terms of improved survival and/or quality of life. In the case of metastatic disease effective chemotherapy has shown to improve survival, but with a median gain survival of 3-4 months. Taken together, this had led to a hesitant attitude towards postoperative recurrence-focused follow-up. Therefore, in most European countries, including the Netherlands, a standardized approach to follow-up after surgery for PDAC is lacking. Furthermore, current PDAC guidelines regarding follow-up are based on expert opinion and other low-level evidence. However, the emergence of more potent local and more effective systemic treatments for PDAC has led to a rising interest in early diagnosis of PDAC recurrence. To detect PDAC recurrence at an early stage and identify patients with good performance status who are most likely to benefit from additional (experimental) treatment, a standardized approach to follow-up with routine imaging and serial serum tumor marker testing is needed. To determine whether early detection of recurrence can lead to improved survival and quality of life, further studies are warranted.

Objective: The main objective is to evaluate the impact of a standardized surveillance, with serial tumor marker testing and routine imaging, on overall survival and quality of life in patients with primary resected PDAC, compared to current non-standardized practice.

Study design: A randomized controlled trial, nested within an existing prospective cohort (Dutch Pancreatic Cancer Project; PACAP) and the United Kingdom (UK) Pancreas Cancer: Observations of Practice and survival; PACOPS) according to the 'trials within cohorts' (TwiCs) design.

Study population: PACAP or PACOPS-participants with histologically confirmed radical resection (R0-R1) of PDAC, who provided informed consent for being randomized in future studies.

Interventions: Standardized surveillance, existing of clinical evaluation, serum cancer antigen (CA) 19-9 testing, and contrast-enhanced computed tomography (CT-) imaging of chest and abdomen every 3 months during the first 2 years after surgery.

Comparison: Non-standardized clinical follow-up.

Endpoints: The main study endpoint is overall survival. The most important secondary endpoint is quality of life. Other secondary endpoints are clinical and radiological patterns of PDAC recurrence, the compliance of patients to our standardized follow-up strategy, the impact of a standardized surveillance on (eligibility for) additional treatment, and the tolerance of additional treatment.

• Study Type: Interventional
• Enrollment (Estimated): 306
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • University Medical Center Groningen
  • Utrecht, Netherlands, 3584 CX
    • University Medical Center Utrecht
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6525 GA
      • Radboud University Medical Center
  • Limburg
    • Maastricht, Limburg, Netherlands, 6229 HX
      • Maastricht UMC
  • Noord-Brabant
    • Eindhoven, Noord-Brabant, Netherlands, 5623 EJ
      • Catharina Ziekenhuis
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1091 AC
      • Onze Lieve Vrouwe Gasthuis
    • Amsterdam, Noord-Holland, Netherlands, 1081 HV
      • Amsterdam University Medical Center VUmc
    • Amsterdam, Noord-Holland, Netherlands, 1105 AZ
      • Amsterdam University Medical Center AMC
  • Overijssel
    • Enschede, Overijssel, Netherlands, 7512 KZ
      • Medisch Spectrum Twente
  • Utrecht
    • Nieuwegein, Utrecht, Netherlands, 3435 CM
      • Sint Antonius Ziekenhuis
• United Kingdom
  • Birmingham, United Kingdom, B15 2TT
    • University of Birmingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Participation in the PACAP and PACOPS-cohort with written informed consent for being randomized in future studies
• Histologically confirmed macroscopically radical resected (R0-R1) pancreatic adenocarcinoma
• Minimum age of 18 years

Exclusion Criteria:

• Exclusion criteria for contrast-enhanced CT-scan, following the protocol of the department of radiology in each affiliated hospital
• Mentally or physically incapable of consent
• Participation in other studies with a study-specific follow-up

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Standardized surveillance; Standardized surveillance strategy with routine imaging and serum tumor marker testing.	Other: Standardized surveillance; Standardized 3-monthly surveillance with routine imaging and serum tumor marker testing.
No Intervention: Non-standardized surveillance; Non-standardized surveillance strategy according to current clinical practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	The interval between the date of PDAC resection and either death from any cause or last follow-up.	From date of PDAC resection until date of death from any cause or date of last follow-up, whichever came first, assessed up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compliance of the standardized surveillance strategy	The percentage of patients that either accepts or refuses participation in the intervention-arm, i.e. is willing to undergo a standardized follow-up regime.	Through completion of patient inclusion, an average of 1.5 years
Recurrence-free interval	The interval between the date of PDAC resection and the date of first radiological signs of recurrence, or last follow-up if recurrence is not observed.	From date of PDAC resection until date of first radiological signs of recurrence, or last follow-up if recurrence is not observed, whichever came first, assessed up to 24 months
Prognostic patient specific characteristics and tumor related factors for disease recurrence		From date of randomization until disease recurrence or last follow-up, assessed up to 24 months
Role of serum tumor marker testing in detecting recurrent PDAC assessed by the calculated diagnostic accuracy values		From date of randomization until disease recurrence or last follow-up, assessed up to 24 months
Eligibility for additional (experimental) treatment at the time of recurrence diagnosis based on the ECOG or Karnofsky performance state, or inclusion criteria for study-related treatment of recurrence		At the time of recurrence diagnosis. Assessed through the study, up to 24 months
Reasons to refrain from treatment for recurrence	e.g. poor condition, patients wish, deteriorated condition, progressive disease, advise treating clinician, death, wait-and-see, age.	At the time the patient is assessed eligible for additional treatment. Assessed through the study, up to 24 months
Patients' tolerance of additional treatment for PDAC recurrence as assessed by incidence of adverse events (graded according to NCI CTCAE Version 5.0)		Through study completion, an average of 2 years
Morbidity associated with diagnostic testing assessed by the side-effects of diagnostic testing (i.e. fear of disease recurrence)		From date of randomization until disease recurrence or last follow-up, whichever came first, assessed up to 24 months
Patient reported non-disease specific health-related Quality of Life (HRQoL) as assessed using the EQ-5D-5L	Part of the Patient Reported Outcome Measures (PROMs) that are being standardly measured in PACAP and PACOPS-participants.	At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year after enrollment in the PACAP and PACOPS-cohort. Assessed through study completion, up to 24 months
Overall costs of a standardized surveillance strategy versus the costs as incurred with the current non-standardized follow-up assessed according to the EQ-5D questionnaire as part of the PACAP and PACOPS-project, and calculated using to a Markov model		After study completion (estimated duration of 3.5 years)
Patient reported chemotherapy-induced peripheral neuropathy as assessed using the EORTC QLQ-CIPN20	Part of the Patient Reported Outcome Measures (PROMs) that are being standardly measured in PACAP and PACOPS-participants.	At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year after enrollment in the PACAP and PACOPS-cohort. Assessed through study completion, up to 24 months
Patient reported Quality of Life as assessed using the happiness, hospital, anxiety and depression scale (HADS)	Part of the Patient Reported Outcome Measures (PROMs) that are being standardly measured in PACAP and PACOPS-participants.	At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year after enrollment in the PACAP and PACOPS-cohort. Assessed through study completion, up to 24 months
Patient reported Quality of Life as assessed using Exocrine Pancreatic Insufficiency (EPI) questionnaire	Part of the Patient Reported Outcome Measures (PROMs) that are being standardly measured in PACAP and PACOPS-participants.	At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year after enrollment in the PACAP and PACOPS-cohort. Assessed through study completion, up to 24 months
Patient reported Quality of Life as assessed using the worry of progression of cancer scale (WOPS)	Part of the Patient Reported Outcome Measures (PROMs) that are being standardly measured in PACAP and PACOPS-participants.	At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year after enrollment in the PACAP and PACOPS-cohort. Assessed through study completion, up to 24 months
Patient reported cancer-specific HRQoL as assessed using the EORTC QLQ-C30	Part of the Patient Reported Outcome Measures (PROMs) that are being standardly measured in PACAP and PACOPS-participants.	At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year after enrollment in the PACAP and PACOPS-cohort. Assessed through study completion, up to 24 months
Patient reported tumor-specific HRQoL as assessed using the EORTC LQPAN26	Part of the Patient Reported Outcome Measures (PROMs) that are being standardly measured in PACAP and PACOPS-participants.	At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year after enrollment in the PACAP and PACOPS-cohort. Assessed through study completion, up to 24 months

Other Outcome Measures

Outcome Measure	Time Frame
Clinical patterns of disease recurrence assessed by the patients symptoms as reported in the electronic patient dossier: explanatory	From date of randomization until disease recurrence or last follow-up, assessed up to 24 months
Clinical patterns of disease recurrence assessed by physicial examination as reported in the electronic patient dossier: explanatory	From date of randomization until disease recurrence or last follow-up, assessed up to 24 months
Clinical patterns of disease recurrence assessed by blood test results as reported in the electronic patient dossier: explanatory	From date of randomization until disease recurrence or last follow-up, assessed up to 24 months
Radiological patterns of disease recurrence assessed by information from imaging reports from the electronic patient dossier: explanatory	From date of randomization until disease recurrence or last follow-up, assessed up to 24 months

Collaborators and Investigators

• Sponsor: UMC Utrecht
• Collaborators: University of Birmingham; Dutch Pancreatic Cancer Group (DPCG)
• Investigators: Principal Investigator: I. Q. Molenaar, MD, PhD, Regional Academic Cancer Center Utrecht (RACU); Principal Investigator: H. C. van Santvoort, MD, PhD, Regional Academic Cancer Center Utrecht (RACU); Principal Investigator: M. G.H. Besselink, MD, PhD, Academic Medical Center - Cancer Center Amsterdam; Principal Investigator: L. A. Daamen, MD, PhD, Regional Academic Cancer Center Utrecht (RACU)

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2021
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: March 17, 2021
• First Submitted That Met QC Criteria: April 30, 2021
• First Posted (Actual): May 6, 2021

Study Record Updates

• Last Update Posted (Actual): September 19, 2024
• Last Update Submitted That Met QC Criteria: September 11, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Follow-up; Standardized Surveillance; CA 19-9; Computed Tomography Scan
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Disease Attributes; Recurrence; Adenocarcinoma
• Other Study ID Numbers: NL67115.041.18; 20-762 (Other Identifier: METC Utrecht)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified data generated during the RADAR-PANC trial will be made available to other researcher upon request from I.Q. Molenaar.
• IPD Sharing Access Criteria: Upon request.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

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