Recurrent Disease Detection After Resection of Pancreatic Adenocarcinoma Using a Standardized Surveillance Strategy: a Nationwide Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 发起方
- UMC Utrecht
- 入组人数
- 202
- 试验地点
- 22
- 主要终点
- Overall survival
研究概览
简要总结
A randomized controlled trial, nested within an existing prospective cohort (Dutch Pancreatic Cancer Project; PACAP) 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.
详细描述
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) according to the 'trials within cohorts' (TwiCs) design.
Study population: PACAP-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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Exclusion criteria for contrast-enhanced CT-scan, following the protocol of the department of radiology in each DPCG-affiliated hospital
- •Mentally or physically incapable of consent
- •Participation in other studies with a study-specific follow-up
结局指标
主要结局
Overall survival
时间窗: 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.
次要结局
- Compliance of the standardized surveillance strategy(Through completion of patient inclusion, an average of 1.5 years)
- 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)
- 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)
- 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(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(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)(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(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)(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(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(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)
研究者
Prof. dr. I.Q. Molenaar, MD, PhD
Principal Investigator
UMC Utrecht