PANcreatic Cancer lOcalized Disease in Frail or Elderly Patients Unfit for Both Chemotherapy and Surgery Treated With Stereotactic Ablative Radiotherapy (PANCOSAR): a Multicenter Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 98
- 试验地点
- 4
- 主要终点
- Overall survival
研究概览
简要总结
SUMMARY Rationale: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, its incidence increases with age. Many patients with localized (non-metastatic) PC have significant comorbidities, advanced age or a poor performance status which preclude chemotherapy and surgery. Because these patients are currently left untreated, it is desirable to find tolerable treatment options for these patients. A short course of high-dose precise radiation therapy i.e. stereotactic ablative body radiotherapy (SABR) may be feasible in these patients. Review of existing SABR literature for PDAC shows high local control rates, with relatively low toxicity and it was demonstrated to be feasible and well tolerated even in elderly patients. It is unknown whether SABR improves outcomes in this group. The main goal of the current study is to investigate if SABR may relieve tumor-related symptoms, postpone a decrease in global QoL and potentially prolong survival in this patient group compared to the current treatment of choice, best supportive care.
Objective: To investigate the potential benefit in survival and quality of life after SABR in patients with localised PDAC for whom no other treatment is available, as compared to controls managed with best supportive care.
Study design: A multicentre randomized controlled trial Study population: Patients with biopsy proven, localized PDAC, unfit for chemotherapy and surgery or those who refuse these treatments. They will be randomized between SABR versus best supportive care.
Intervention: consists of SABR to the primary tumour in 5 fractions of 8 Gy. Main study endpoints: Primary endpoint is the overall survival rate at six months (from randomization). Secondary endpoints include the evaluation of time to decreased global quality of life (QoL, using the QLQ- C30 and EORTC-PAN26), NRS pain response and Ca19.9 response, acute and subacute toxicity using CTCAEv5.0 and progression-free survival in the treated patients using imaging.
It is hypothesized that in frail patients with PDAC, SABR may relieve tumor-related symptoms, improve the quality of life and prolong survival compared to best supportive care. Its aim is to investigate the outcomes of SABR with respect to overall survival, pain response, toxicity and quality of life in patients with non-metastasized PDAC for whom standard radical treatment in the form of surgery or chemotherapy is either too toxic, not possible due to comorbidities, or is refused.
详细描述
This study is a prospective multicenter randomized controlled trial according to the 'cohort multiple randomized controlled trial (cmRCT)'-design. This study will be nested within the existing prospective observational PACAP cohort (the Dutch Pancreatic Cancer Project; PACAP), in which all 48 centers of the Dutch Pancreatic Cancer Group (DPCG) participate. PACAP-participants have provided informed consent for being randomized in cmRCTs. Patients who are randomized to the interventional arm will be approached for informed consent. Patients who are randomized in the control arm will not be approached as they already provided informed consent(12) .
PACAP(13) is a nationwide registration outcome project including the Dutch Pancreatic Cancer Audit, a nationwide Expert Panel and the Dutch Pancreas Biobank (PancreasParel). The PACAP-cohort is designed according to the cohort multiple randomized controlled trial (cmRCT) design, meaning a large observational cohort of patients, which can be used as a multiple trials facility. Participants in the PACAP-cohort have provided general informed consent for collection of specific data on demographics, quality of life and clinical, laboratory and radiological findings during follow-up after randomization.
To investigate whether SABR relieves tumor-related symptoms such as pain, improves the quality of life and prolongs survival compared to best supportive care, randomization is performed within PACAP-participants with primary pathology-proven non-metastasized PC for whom currently no treatment is available other than palliative care, or those who choose to refrain from radical treatment.
Population (base)
In current clinical practice, there remains a substantial group of patients with non- metastasized PDAC who are medically inoperable based on compromised physiological reserve and/or comorbidities, for whom currently no treatment is available other than best supportive care, or who choose to refrain from radical treatment in the form of surgery or chemotherapy. According to NCR data, this group consists of approximately 300 patients per year. These patients may, however be fit enough to undergo a short course of SABR.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 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
- •Pathology proven localised (non-metastasized) PDAC
- •Patients unfit for both surgery and systemic chemotherapy (i.e. KPS 50-70; WHO 2) • • Patients who choose to refrain from surgery or chemotherapy
- •Written informed consent
排除标准
- •Age <18 years
- •Distant metastasis
- •Imminent bowel obstruction
- •Active bleeding
- •Uncontrolled infection
- •Contra-indications for MRI (only for VUmc and UMCU)
- •Pacemakers or implanted defibrillators, deep brain stimulators, cochlear implants.
- •Patients who have a metallic foreign body in their eye, or who have an aneurysm clip in their brain, cannot have an MRI scan since the magnetic field may dislodge the metal
- •Patients with severe claustrophobia not able to tolerate an MRI scan
- •Patients with a non-MR-compatible (hip/knee/jaw) prosthesis
结局指标
主要结局
Overall survival
时间窗: six months after randomization
The primary endpoint is to compare survival at six months in both study arms, measured from the time of randomization.
次要结局
- Global quality of life(prior to treatment, 3-6-12 months after randomization)
- Pain score(prior to treatment, 3-6-12 months after randomization)
- Quality of Life related to symptoms caused by cancer(prior to treatment, 3-6-12 months after randomization)
- Level of CA19.9(prior to treatment, 3, 6 and 12 months after treatment)
- Acute toxicity due to treatment(prior to treatment, 5th fraction, at 3 and 6 weeks (telephone consultation by Radiation Oncologist), 3-6-12 months after randomization)
- Late toxicity due to treatment(prior to treatment, 5th fraction, at 3 and 6 weeks (telephone consultation by Radiation Oncologist), 3-6-12 months after randomization)
- WHO performance score(prior to treatment, 3-6-12 months after randomization)
- Quality of Life related to symptoms caused by pancreatic cancer(prior to treatment, 3-6-12 months after randomization)
- Progression of disease (local and distant)(3, 6 and 12 months after randomization)
研究者
Anna Bruynzeel
MD PhD
Amsterdam UMC, location VUmc