Randomized Prospective Trial of Breast Cancer Locator Guided vs. Wire Localized Partial Mastectomy for Breast Cancer

乳腺癌定位器引导与钢丝定位部分乳房切除术治疗乳腺癌的随机前瞻性试验

基本信息

批准号：
10080991
负责人：
Venkataramanan Krishnaswamy
金额：
$ 100.77万
依托单位：
CAIRNSURGICAL, INC.
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10080991
关键词：
3D Print Adoption Anatomy Automation Award Breast Breast-Conserving Surgery Businesses Cells Classification Clinical Clinical Research Clinical Trials Complex Computer software Cost Savings Coupled Cues Custom Data Device Designs Devices Disease Effectiveness Enrollment Evaluation Excision FDA approved Financial Contribution Funding Generations Geometry Health Care Costs Healthcare Hospitals Image Individual Infrastructure Institution Investigation Investments Label Localized Malignant Neoplasm Magnetic Resonance Imaging Malignant Neoplasms Marketing Mastectomy Medical Medical Device Meta-Analysis Modeling Noninfiltrating Intraductal Carcinoma Operative Surgical Procedures Outcome Patient-Focused Outcomes Patients Phase Plastics Positioning Attribute Preparation Printing Privatization Procedures Process Production Protocols documentation Publishing Randomized Randomized Clinical Trials Randomized Controlled Trials Recurrence Request for Applications Research Research Design Safety Savings Secure Series Site Standardization Sterilization Supination Surface Surgeon Surgical Oncology Surgical margins Technology Testing Time Validation arm base biomaterial compatibility clinical research site commercialization cost cost effectiveness cost efficient design experience health care economics health care settings image guided improved innovation malignant breast neoplasm manufacturing process meetings novel novel therapeutics product development prognostic prospective research and development scale up service providers standard of care success trial design tumor

项目摘要

PROJECT SUMMARY/ABSTRACT: CairnSurgical, Inc., a Dartmouth spin-off company, will conduct a prospective, multicenter, 1:1 randomized, controlled trial designed to evaluate the safety and effectiveness of its Breast Cancer Locator (BCL) device in subjects with non-palpable invasive breast cancer or ductal carcinoma in situ (DCIS) under an investigational device exemption (IDE) recently approved by the FDA (Nov 2019). Subjects will be randomized to breast conserving surgery (BCS) utilizing either BCL or wire localization (WL) to guide surgery. BCL is a novel patient- specific, guidance device designed for use in breast conserving surgery (BCS) to (i) eliminate wire localization – a moderately effective, somewhat costly and certainly inconvenient procedure for patients and surgeons – and concomitantly to (ii) reduce positive margin rates (PMRs) and subsequent re-excision surgeries – a significant but unnecessary burden not only on patients but also on the cost of healthcare. In the proposed Direct to Phase II application, Cairn will (i) support 7 clinical sites as part of a multi-center pivotal randomized controlled trial, RCT, (in up to 15 centers; remaining support will derive from recently secured private investment) in 438 subjects (219 per arm) to generate evidence that PMR following BCS using the BCL is reduced relative to standard of care (WL), (ii) evaluate BCL cost-effectiveness through a healthcare economics study to generate data on use, out-comes, and savings to hospitals and payors that support market adoption, and (iii) file a de novo classification request to FDA for BCL PMR reduction marketing claims relative to WL. Based on preliminary results from a recently completed Dartmouth randomized prospective trial23 and several published RCTs of wire localization (see Table 1 in Research Strategy), we have estimated PMR in the WL arm to be 19%. The proposed study design allows definitive evaluation of superiority of BCL, with power sufficient to detect a clinically meaningful, 40% reduction in PMR, from 19% to 11.2%. In preparation for the proposed RCT, CairnSurgical has obtained IDE approval from FDA after successfully completing necessary product development and testing under design controls including, sterilization validation and biocompatibility testing. In addition, we have developed manufacturing processes to fabricate BCL devices under regulatory controls required for clinical trial use and achieve sufficient throughput scale-up by vertically integrating device fabrication, in-process inspection, sterilization and clean-room packaging capabilities. Positive margin rates associated with contemporary BCS are high (~18%-22.3%), and cause significant strains on patients and the cost of breast healthcare. Meta-analyses of the impact of surgical margins on local recurrence also confirm that negative margins have a positive prognostic effect. Thus, CairnSurgical is well positioned to develop and commercialize a potentially practice-changing approach to BCS that improves clinical outcomes for patients.

项目概要/摘要：达特茅斯分拆公司 CairnSurgical, Inc. 将进行一项前瞻性、多中心、1:1 随机、旨在评估其乳腺癌定位器 (BCL) 设备的安全性和有效性的对照试验患有不可触及的浸润性乳腺癌或导管原位癌 (DCIS) 的研究对象 FDA 最近批准了设备豁免 (IDE)（2019 年 11 月）。受试者将被随机分配到乳房。利用 BCL 或导丝定位 (WL) 来指导手术的保留手术 (BCS) 是一种新型患者。专为保乳手术 (BCS) 使用而设计的特定引导装置，以 (i) 消除导丝定位 – 对于患者和外科医生来说，这是一种效果中等、成本较高且肯定不方便的手术 – 同时 (ii) 降低切缘阳性率 (PMR) 和随后的再切除手术 – 不仅对患者而且对医疗保健成本造成重大但不必要的负担。直接进入 II 期申请，Cairn 将 (i) 支持 7 个临床中心，作为多中心关键随机试验的一部分对照试验、RCT（最多 15 个中心；剩余支持将来自最近获得的私人对 438 名受试者（每组 219 名受试者）进行投资），以生成证据表明使用 BCL 进行 BCS 后的 PMR 是相对于护理标准 (WL) 降低，(ii) 通过医疗保健经济学评估 BCL 成本效益研究为医院和付款人生成有关使用、结果和节省的数据，以支持市场采用， (iii) 向 FDA 提交与 WL 相关的 BCL PMR 降低营销声明的从头分类请求。基于最近完成的达特茅斯前瞻性随机试验23和多项研究的初步结果发表了线定位的 RCT（参见研究策略中的表 1），我们估计了 WL 中的 PMR 所提出的研究设计允许对 BCL 的优越性进行明确的评估。足以检测到有临床意义的 PMR 降低 40%，从 19% 降至 11.2%。拟议的 RCT，CairnSurgical 在成功完成必要的要求后已获得 FDA 的 IDE 批准设计控制下的产品开发和测试，包括灭菌验证和生物相容性此外，我们还开发了在监管范围内制造 BCL 设备的制造工艺。临床试验使用所需的控制，并通过垂直整合设备实现足够的通量放大制造、过程检验、灭菌和洁净室包装能力。与当代 BCS 相关的比例很高（~18%-22.3%），并对患者和患者造成重大压力乳房保健费用的荟萃分析也证实了手术切缘对局部复发的影响。因此，负切缘具有积极的预后作用，CairnSurgical 处于有利的发展和地位。将一种可能改变实践的 BCS 方法商业化，改善患者的临床结果。