Clinical trial NCT04875325: Recurrent Disease Detection After Resection of Pancreatic Adenocarcinoma Using a Standardized Surveillance Strategy
Official title: Recurrent Disease Detection After Resection of Pancreatic Adenocarcinoma Using a Standardized Surveillance Strategy: a Nationwide Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Resectable Pancreatic Ductal Adenocarcinoma
Recurrent Pancreatic Ductal Adenocarcinoma
Keywords: Standardized Surveillance
Follow-up
CA 19-9
Computed Tomography Scan
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: Dutch Pancreatic Cancer Group (DPCG)
name: University of Birmingham
First posted: 2021-05-06
Enrollment: 306
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Trials within Cohorts (TwiCs)
Primary purpose: OTHER

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall survival
timeFrame: 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 outcomes:
measure: Compliance of the standardized surveillance strategy
timeFrame: Through completion of patient inclusion, an average of 1.5 years
measure: Recurrence-free interval
timeFrame: 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
measure: Prognostic patient specific characteristics and tumor related factors for disease recurrence
timeFrame: From date of randomization until disease recurrence or last follow-up, assessed up to 24 months
measure: Role of serum tumor marker testing in detecting recurrent PDAC assessed by the calculated diagnostic accuracy values
timeFrame: From date of randomization until disease recurrence or last follow-up, assessed up to 24 months
measure: 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
timeFrame: At the time of recurrence diagnosis. Assessed through the study, up to 24 months
measure: Reasons to refrain from treatment for recurrence
timeFrame: At the time the patient is assessed eligible for additional treatment. Assessed through the study, up to 24 months
measure: Patients' tolerance of additional treatment for PDAC recurrence as assessed by incidence of adverse events (graded according to NCI CTCAE Version 5.0)
timeFrame: Through study completion, an average of 2 years
measure: Morbidity associated with diagnostic testing assessed by the side-effects of diagnostic testing (i.e. fear of disease recurrence)
timeFrame: From date of randomization until disease recurrence or last follow-up, whichever came first, assessed up to 24 months
measure: Patient reported non-disease specific health-related Quality of Life (HRQoL) as assessed using the EQ-5D-5L
timeFrame: 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
measure: 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
timeFrame: After study completion (estimated duration of 3.5 years)
measure: Patient reported chemotherapy-induced peripheral neuropathy as assessed using the EORTC QLQ-CIPN20
timeFrame: 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
measure: Patient reported Quality of Life as assessed using the happiness, hospital, anxiety and depression scale (HADS)
timeFrame: 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
measure: Patient reported Quality of Life as assessed using Exocrine Pancreatic Insufficiency (EPI) questionnaire
timeFrame: 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
measure: Patient reported Quality of Life as assessed using the worry of progression of cancer scale (WOPS)
timeFrame: 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
measure: Patient reported cancer-specific HRQoL as assessed using the EORTC QLQ-C30
timeFrame: 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
measure: Patient reported tumor-specific HRQoL as assessed using the EORTC LQPAN26
timeFrame: 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 outcomes:
measure: Clinical patterns of disease recurrence assessed by the patients symptoms as reported in the electronic patient dossier: explanatory
timeFrame: From date of randomization until disease recurrence or last follow-up, assessed up to 24 months
measure: Clinical patterns of disease recurrence assessed by physicial examination as reported in the electronic patient dossier: explanatory
timeFrame: From date of randomization until disease recurrence or last follow-up, assessed up to 24 months
measure: Clinical patterns of disease recurrence assessed by blood test results as reported in the electronic patient dossier: explanatory
timeFrame: From date of randomization until disease recurrence or last follow-up, assessed up to 24 months
measure: Radiological patterns of disease recurrence assessed by information from imaging reports from the electronic patient dossier: explanatory
timeFrame: From date of randomization until disease recurrence or last follow-up, assessed up to 24 months
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
state: Gelderland
city: Maastricht
country: Netherlands
facility: Maastricht UMC
state: Limburg
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis
state: Noord-Brabant
city: Amsterdam
country: Netherlands
facility: Amsterdam University Medical Center VUmc
state: Noord-Holland
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwe Gasthuis
state: Noord-Holland
city: Amsterdam
country: Netherlands
facility: Amsterdam University Medical Center AMC
state: Noord-Holland
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
state: Overijssel
city: Nieuwegein
country: Netherlands
facility: Sint Antonius Ziekenhuis
state: Utrecht
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Birmingham
country: United Kingdom
facility: University of Birmingham
Study officials:
affiliation: Regional Academic Cancer Center Utrecht (RACU)
name: I. Q. Molenaar, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Regional Academic Cancer Center Utrecht (RACU)
name: H. C. van Santvoort, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Academic Medical Center - Cancer Center Amsterdam
name: M. G.H. Besselink, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Regional Academic Cancer Center Utrecht (RACU)
name: L. A. Daamen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: