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

预防不治之症：预防进展为胰腺癌试验（3P-C 试验）

• 批准号: 10242845
• 负责人: Peter J Allen
• 金额: $ 61.48万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-20 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10242845
• 关键词: Adjuvant; Antibodies; Biological Markers; Cancer Etiology; Cessation of life; Chemoprevention; Clinical Data; Clinical Trials; Cyclooxygenase Inhibitors; Cyst; Cyst Fluid; Data; Development; Diagnosis; Diagnostic; Diagnostic radiologic examination; Disease; Disease Outcome; Double-Blind Method; Early Diagnosis; Endoscopic Ultrasonography; Enrollment; Excision; Failure; Gelatinase B; General Hospitals; Gland; Goals; Heterogeneity; Human; Image; Image Analysis; Inflammation; Inflammation Mediators; Inflammatory; Interleukin-4; Laboratories; Lesion; Liquid substance; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of pancreas; Massachusetts; Measurement; Measures; Modeling; Monitor; Mucinous Neoplasm; Pancreas; Pancreatectomy; Pancreatic Adenocarcinoma; Pancreatic cystic neoplasia; Papillary; Patient-Focused Outcomes; Patients; Pattern; Placebos; Pre-Clinical Model; Prevention; Probability; Process; Randomized; Recommendation; Research; Risk; Solid; Stage at Diagnosis; Suggestion; Sulindac; Systemic Therapy; Techniques; Testing; Therapeutic; United States; University Hospitals; Variant; X-Ray Computed Tomography; arm; biomarker panel; cancer invasiveness; cancer therapy; disorder prevention; effectiveness evaluation; first-in-human; high risk; improved; improved outcome; inflammatory marker; novel strategies; pancreas development; phase II trial; prevent; primary endpoint; quantitative imaging; radiomics; secondary endpoint; treatment arm; treatment effect; tumor; tumor progression

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.

项目摘要 胰腺癌将于2019年在美国大约55,000人中诊断出。几乎所有这些 由于诊断后的晚期和电流无效性，患者将死于这种疾病 系统性疗法。当前的诊断和治疗策略的缺点体现了一个事实 即使在开发可识别转移性疾病之前诊断出患者（<占15％的15％ 患者），并接受操作切除和调整全身疗法的治疗，五年的可能性 生存率约为10％。迫切需要采取新颖的策略来改善患者的预后 疾病。 胰腺的导管内乳头肿瘤（IPMN）是囊性肿瘤，代表唯一 胰腺癌的射线照相上可识别的前体病变。 IPMN是一个“全gland”过程，这是 知道对IPMN进行部分胰腺切除术的患者患癌症的风险增加 在胰腺残余物中。因此，建议患有部分部分的患者 非侵入性IPMN的胰腺切除术是其胰腺的连续射线照相和/或内窥镜监测 剩。我们小组的最新数据表明，大约25％的患者将发展X射线照相 IPMN进展的迹象在切除的三到四年内。在我们的四个中心（杜克大学）之间 约翰·霍普金斯大学医院，马萨诸塞州纪念斯隆·凯特林医院）我们是 目前遵循已有450多名IPMN切除的患者。这些患者非常适合 进行化学预防试验。 这项多机构研究工作的目的是进行第一个人类化学预防试验 胰腺腺癌。进行了部分胰腺切除术的患者，并被发现 具有高风险IPMN，将有资格参加此随机双盲安慰剂控制阶段II期试验（100 患者/手臂）。该试验将利用选择性COX抑制剂Sulindac，已证明是 在临床前模型中预防胰腺癌的进展非常有效。来自我们的临床数据 小组和其他人表明，患者的影响与进展之间有很强的联系 使用IPMN和Sulindac已显示这些囊性前体患者的IPMN大小 病变。主要终点将是三年后放射线摄影进展的速率。患者会 严格监测，每六个月使用替代的CT成像和内窥镜超声/流体吸入。 次要终点将包括：（1）评估该治疗对囊肿液体炎症的影响 标记和先前开发的囊肿流体生物标志物面板，以及（2）一种新颖的射线照相方法 评估（放射组学），用于早期检测到恶性肿瘤的进展。