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: 10478007
• 负责人: John M DeWitt
• 金额: $ 40.97万
• 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 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10478007
• 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; Double-Blind Method; Dyes; Early Intervention; Endoscopic Ultrasonography; Endoscopy; Epidemic; 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; radiological imaging; 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.

难以表征和治疗的癌前胰腺囊肿越来越多 由于成像技术的进步和老化，过去二十年在美国发现了 人口。随着美国高致命性胰腺癌发病率的上升，对 安全有效地治疗具有恶变潜力的胰腺囊肿是一项重大公共卫生问题 忧虑。虽然患者历来仅限于放射线监测或可能 危险的手术作为处理这些囊肿的不良方法，内窥镜超声 引导细针注射（EUS-FNI）已成为一种微创、安全且有效的方法 早期干预的方法。对于当今 EUS 引导下的胰腺囊肿治疗，通常需要护理 包括用乙醇灌洗。然而，专家们一致认为，观察到的不良事件 (AE) 治疗期间由于乙醇的使用。近期，基于安全隐患 乙醇的使用，以及与紫杉醇输注相关的有希望的治疗结果，我们的 研究小组创建了一种无乙醇 (EF) 联合化疗疗法，其中包括 混合物——紫杉醇和吉西他滨——专门针对胰腺囊性病变而设计 通过 EUS 引导注射进行肿瘤形成。我们的团队完成了对这种新颖治疗策略的测试 2017 年的一项初步随机试验表明，EF 灌洗（即生理盐水）与组合 化疗与相同的化疗方法相比，同样有效，而且安全得多。 包括乙醇灌洗（EL）。在这项提案中，我们的目标是扩大试点研究的规模， 进行一项大型且明确的多中心试验，这将是第一个资助的随机对照试验 EL 治疗至无乙醇 (EF) 治疗联合输注化疗药物 代理。所有受试者都将进行合格的囊性病变抽吸和排空，并接受 3 个月时进行随访，12 个月时进行最终成像。我们将随机分配100 患有胰腺囊肿的成年患者分为两个研究组：(1) 乙醇灌洗 (EL)：EL，然后 输注紫杉醇-吉西他滨混合物，或 (2) 无乙醇 (EF)：盐水灌洗，然后 通过输注相同的紫杉醇-吉西他滨混合物。我们假设 EF 治疗将 不良事件显着减少，囊肿消融完全解决 并不逊色于 EL 治疗。如果 EF 干预被证明不劣于，并且 比 EL 治疗安全得多，它将验证 EUS-FNI 作为一种可行的治疗方式 用于对癌前囊肿进行干预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，可能会改变治疗决策 患者制定并改变卓越中心提供的治疗方案。

项目成果

The Durability of EUS-Guided Chemoablation of Mucinous Pancreatic Cysts: A Long-Term Follow-Up of the CHARM trial.

EUS引导的粘液性胰腺囊肿的化疗的耐用性：魅力试验的长期随访。

• DOI: 10.1016/j.cgh.2021.03.041
• 发表时间: 2022-03
• 期刊: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
• 作者: Lester C;Walsh L;Hartz KM;Mathew A;Levenick JM;Headlee BD;Heisey HD;Birkholz JH;Dixon M;Maranki JL;Gusani NJ;Dye CE;Moyer MT
• 通讯作者: Moyer MT

High-risk main-duct intraductal papillary mucinous neoplasm successfully treated with EUS-guided chemoablation.

• DOI: 10.1016/j.vgie.2020.07.022
• 发表时间: 2020-12
• 期刊: VideoGIE : an official video journal of the American Society for Gastrointestinal Endoscopy
• 作者: Hartz KM;Dixon MEB;Levenick J;Moyer MT
• 通讯作者: Moyer MT