CHARM 2: Chemotherapy for ablation and resolution of mucinous pancreatic cysts: a prospective, randomized, double-blind, multi-center clinical trial

魅力 2：化疗消融和解决粘液性胰腺囊肿：一项前瞻性、随机、双盲、多中心临床试验

• 批准号: 10002201
• 负责人: John M DeWitt
• 金额: $ 43.15万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10002201
• 关键词: Abdominal Pain; Ablation; Admixture; Adult; Adverse event; Alcohol consumption; Aspirate substance; Cancer Etiology; Caring; Cessation of life; Clinical; Combination Drug Therapy; Cyst; Cystic Lesion; Diagnosis; Diagnostic radiologic examination; Double-Blind Method; Dyes; Early Intervention; Endoscopic Ultrasonography; Endoscopy; Epidemic; Estrogen receptor positive; Ethanol; Excision; Extravasation; Funding; Gastroenterology; General Population; Hospitalization; Image; Imaging Techniques; In complete remission; Incidence; Infusion procedures; Injections; Intervention; Investigation; Irrigation; Lesion; Link; Magnetic Resonance Imaging; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of pancreas; Methods; Modality; Mucinous; Multi-Institutional Clinical Trial; Multicenter Trials; Needles; Newly Diagnosed; Operative Surgical Procedures; Paclitaxel; Pancreatectomy; Pancreatic Cyst; Pancreatic cystic neoplasia; Patients; Pharmacology; Pilot Projects; Prevalence; Procedures; Public Health; Publishing; Qualifying; Randomized; Randomized Controlled Trials; Relative Risks; Research; Resolution; Risk; Safety; Saline; Surgical Oncology; Testing; Time; Tissues; United States; Weight; X-Ray Computed Tomography; acute pancreatitis; adverse event risk; aging population; base; chemotherapeutic agent; chemotherapy; clinically significant; cost; design; effective therapy; experience; follow-up; gemcitabine; high risk; malignant breast neoplasm; mortality; multidisciplinary; novel; premalignant; prospective; public health relevance; randomized trial; standard of care; success; treatment comparison; treatment group; treatment strategy; trial comparing; two-arm study

Pre-malignant pancreatic cysts that are difficult to characterize and treat are increasingly discovered in the US over the last two decades due to advances in imaging and an aging population. With the incidence of highly lethal pancreatic cancer rising in the US, intervening on pancreatic cysts with malignant potential in a safe and effective way is a major public health concern. While patients have been historically limited to radiographic surveillance or potentially hazardous surgery as undesirable methods of managing these cysts, endoscopic ultrasound guided fine needle injection (EUS-FNI) has emerged as a less-invasive, safe and effective method of early intervention. For EUS-guided treatment of pancreatic cysts today, care typically includes lavage with ethanol. However, experts agree that adverse events (AEs) observed during treatment are due to ethanol use. Recently, based on the safety concerns surrounding ethanol use, as well as the promising treatment findings linked to the infusion of paclitaxel, our team created an ethanol-free (EF), combination chemotherapy treatment consisting of an admixture—paclitaxel and gemcitabine—specifically designed to target pancreatic cystic neoplasia by EUS-guided injection. Our team completed testing of this novel treatment strategy in 2017 as a preliminary randomized trial, showing that EF lavage (i.e., saline) with combination chemotherapy was as effective, and far safer, than the same chemotherapy treatment with the inclusion of ethanol lavage (EL). In this proposal, our aim is increase the scale of our pilot study, conducting a large and definitive multi-center trial that will be the first funded RCT to compare treatment with EL to ethanol-free (EF) treatment with combination infusion of chemotherapeutic agents. All subjects will have qualifying cystic lesions aspirated and evacuated, and undergo a follow-up procedure at 3 months and final imaging at 12 months. We will randomly assign 100 adult patients with pancreatic cysts to two study arms: (1) Ethanol lavage (EL): EL, followed by infusion of a paclitaxel-gemcitabine admixture, or (2) Ethanol Free (EF): saline lavage, followed by infusion of the same paclitaxel-gemcitabine admixture. We hypothesize that EF treatment will result in significantly fewer adverse events and will have complete cyst ablation resolution rates that are not inferior to EL treatment. If the EF intervention proves to be non-inferior to, and significantly safer than, treatment with EL, it will validate EUS-FNI as a viable treatment modality for intervening on pre-malignant cysts and will change the standard of care for pancreatic cyst management. Critically, if EF treatment is successful, it may alter the treatment decisions that patients make and change the treatment options that centers of excellence offer.

难以表征和治疗的恶性前胰腺囊肿越来越多 由于成像和衰老的进步，在过去的二十年中在美国发现 人口。随着美国高度致命的胰腺癌的发生，美国介入 以安全有效的方式具有恶性潜力的胰腺囊肿是主要的公共卫生 忧虑。尽管历史上一直限于放射线检查或潜在 有害手术是管理这些囊肿的不良方法，内窥镜超声 指导性细针注射（EUS-FNI）已成为一种侵入性，安全有效的 早期干预的方法。对于当今胰腺囊肿的EUS引导的治疗，通常会护理 包括乙醇的灌洗。但是，专家认为观察到的不利事件（AES） 治疗期间是由于使用乙醇。最近，基于周围的安全问题 乙醇的使用，以及与紫杉醇输注有关的有望治疗结果，我们 团队创建了无乙醇（EF），组合化学疗法治疗，由 混合物 - 帕列赛和吉西他滨 - 专门设计用于靶向胰腺囊性的 EUS引导的注射肿瘤。我们的团队完成了这种新颖治疗策略的测试 在2017年作为初步随机试验，表明EF灌洗（即盐水）具有组合 化学疗法比与使用相同的化学疗法治疗一样有效，更安全 包括乙醇灌洗（EL）。在此提案中，我们的目标是提高了试点研究的规模， 进行大型且确定的多中心试验，该试验将是第一个资助的RCT 用EL进行无乙醇（EF）治疗，并结合化学治疗 代理商。所有受试者都将使囊性病变被抽吸和疏散，并经历A 在3个月且最终成像为12个月时的后续程序。我们将随机分配100 成年患者胰腺囊肿到两个研究臂：（1）乙醇灌洗（EL）：EL，其次是 注入紫杉醇 - 甲甲苯滨混合物，或（2）乙醇（EF）：盐水灌洗，随后 通过输注相同的紫杉醇 - 吉马替滨混合物。我们假设EF治疗将 导致广告事件大大减少，并将具有完整的囊肿消融率 不如EL治疗不如EL。如果EF干预被证明不属于，并且 比用EL的治疗更安全，它将验证EUS-FNI作为可行的治疗方式 用于介入前机构囊肿，并将改变胰腺囊肿的护理标准 管理。至关重要的是，如果EF治疗成功，它可能会改变治疗决定 患者做出和更改卓越中心提供的治疗选择。