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.

恶性前胰腺囊肿越来越难诊断和治疗