Preventing an Incurable Disease: The Prevention of Progression to Pancreatic Cancer Trial (The 3P-C Trial)

项目总结 2019年，美国将有大约55000人被诊断为胰腺癌。几乎所有这些 由于诊断的晚期和电流的无效，患者将死于这种疾病。 系统性治疗。事实证明了当前诊断和治疗策略的缺陷 即使患者在发生可识别的转移性疾病之前被诊断出来(15%) 患者)，并接受手术切除和辅助系统治疗，五年的概率 存活率约为10%。迫切需要新的策略来改善这方面的患者结果 疾病。 胰腺导管内乳头状黏液性肿瘤(IPMN)是囊性肿瘤，它是唯一 胰腺癌的放射学可识别的前驱病变。IPMN是一个“整个腺体”的过程，它是 已知因IPMN接受胰腺部分切除术的患者患癌症的风险增加 在胰腺残留物中。正因为如此，对部分患者的建议 胰腺切除术治疗非侵袭性IPMN是对其胰腺的连续放射学和/或内窥镜监测 残余物。来自我们小组的最新数据显示，大约25%的患者将发生放射学检查 IPMN在切除后三到四年内有进展的迹象。在我们的四个中心(杜克大学 医院，约翰霍普金斯大学医院，马萨诸塞州综合医院，纪念斯隆·凯特林)我们是 目前跟踪了450多名因IPMN而接受手术的患者。这些病人非常适合 进行化学预防试验。 这项多机构研究的目标是进行首例人类化学预防试验。 胰腺癌。接受部分胰腺切除的患者，并被发现 有高风险的IPMN，将有资格参加这项随机双盲安慰剂对照II期试验(100 患者/手臂)。这项试验将使用选择性COX抑制剂舒林酸，它已被证明是 在临床前模型中非常有效地防止进展为胰腺癌。来自我们的临床数据 研究小组和其他人已经证明了炎症和患者病情进展之间的强烈联系 使用IPMN和舒林酸已被证明可以缩小患有这些囊性前体的患者的IPMN大小 损伤。主要终点将是三年后的放射学进展速度。病人将会是 严密监测，每六个月交替进行CT成像和内窥镜超声/液体抽吸。 次要终点包括：(1)评估该疗法对囊液炎症的影响。 标记物和先前开发的囊液生物标记物组合，以及(2)一种新的放射成像方法 早期发现恶变的评估(放射组学)。

PROJECT SUMMARY Pancreatic cancer will be diagnosed in approximately 55,000 people in the U.S. in 2019. Nearly all of these patients will die from this disease because of the late stage at diagnosis and the ineffectiveness of current systemic therapies. The shortcomings of current diagnostic and therapeutic strategies is exemplified by the fact that even when patients are diagnosed prior to the development of identifiable metastatic disease (<15% of patients) and are treated with operative resection and adjuvant systemic therapy, the probability of five-year survival is approximately 10%. There is an urgent need for novel strategies to improve patient outcomes for this disease. Intraductal papillary mucinous neoplasms (IPMN) of the pancreas are cystic tumors that represent the only radiographically identifiable precursor lesion of pancreatic cancer. IPMN is a “whole-gland” process, and it is known that patients who undergo partial pancreatectomy for IPMN have an increased risk of developing cancer in the pancreatic remnant. Because of this, recommendations for patients who have undergone partial pancreatectomy for non-invasive IPMN is serial radiographic and/or endoscopic surveillance of their pancreatic remnant. Recent data from our group has shown that approximately 25% of patients will develop radiographic signs of IPMN progression within three to four years of resection. Between our four centers (Duke University Hospital, Johns Hopkins University Hospital, Massachusetts General Hospital, Memorial Sloan Kettering) we are currently following over 450 patients who have undergone resection for IPMN. These patients are ideally suited for a chemoprevention trial. The goal of this multi-institutional research effort is to perform the first-in-human chemoprevention trial for pancreatic adenocarcinoma. Patients who have undergone partial pancreatectomy, and have been found to have high-risk IPMN, will be eligible for this randomized double-blind placebo controlled Phase II trial (100 patients/arm). This trial will utilize the selective COX inhibitor sulindac, which has been demonstrated to be highly effective in preventing progression to pancreatic cancer in pre-clinical models. Clinical data from our group and others have demonstrated a strong association between inflammation and progression in patients with IPMN, and sulindac has been shown to decrease the size of IPMN in patients with these cystic precursor lesions. The primary endpoint will be the rate of radiographic progression after three years. Patients will be closely monitored, with alternating CT imaging and endoscopic ultrasound/fluid aspiration every six months. Secondary endpoints will include: (1) assessment of the effects of this treatment on cyst fluid inflammatory markers, and a previously developed cyst fluid biomarker panel, and (2) a novel approach to radiographic assessment (radiomics) for early detection of progression to malignancy.