Recurrent Pancreatic Ductal Adenocarcinoma, Resectable Pancreatic Ductal Adenocarcinoma
Conditions
Keywords
Standardized Surveillance, Follow-up, CA 19-9, Computed Tomography Scan
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.
Interventions
OTHERStandardized surveillance
Standardized 3-monthly surveillance with routine imaging and serum tumor marker testing.
Sponsors
Dutch Pancreatic Cancer Group (DPCG)
University of Birmingham
UMC Utrecht
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
Trials within Cohorts (TwiCs)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | 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 | The interval between the date of PDAC resection and either death from any cause or last follow-up. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Patient reported Quality of Life as assessed using Exocrine Pancreatic Insufficiency (EPI) questionnaire | 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 | Part of the Patient Reported Outcome Measures (PROMs) that are being standardly measured in PACAP and PACOPS-participants. |
| Patient reported Quality of Life as assessed using the worry of progression of cancer scale (WOPS) | 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 | Part of the Patient Reported Outcome Measures (PROMs) that are being standardly measured in PACAP and PACOPS-participants. |
| Patient reported cancer-specific HRQoL as assessed using the EORTC QLQ-C30 | 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 | Part of the Patient Reported Outcome Measures (PROMs) that are being standardly measured in PACAP and PACOPS-participants. |
| Patient reported tumor-specific HRQoL as assessed using the EORTC LQPAN26 | 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 | Part of the Patient Reported Outcome Measures (PROMs) that are being standardly measured in PACAP and PACOPS-participants. |
| Compliance of the standardized surveillance strategy | Through completion of patient inclusion, an average of 1.5 years | 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. |
| Recurrence-free interval | 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 | 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. |
| 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 | At the time the patient is assessed eligible for additional treatment. Assessed through the study, up to 24 months | e.g. poor condition, patients wish, deteriorated condition, progressive disease, advise treating clinician, death, wait-and-see, age. |
| 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 | 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 | Part of the Patient Reported Outcome Measures (PROMs) that are being standardly measured in PACAP and PACOPS-participants. |
| 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 | 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 | Part of the Patient Reported Outcome Measures (PROMs) that are being standardly measured in PACAP and PACOPS-participants. |
| Patient reported Quality of Life as assessed using the happiness, hospital, anxiety and depression scale (HADS) | 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 | Part of the Patient Reported Outcome Measures (PROMs) that are being standardly measured in PACAP and PACOPS-participants. |
Other
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
Countries
Netherlands, United Kingdom
Outcome results
None listed