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

项目摘要/摘要： 从达特茅斯分拆出来的凯恩外科公司将进行一项前瞻性、多中心、1：1随机、 旨在评估其乳腺癌定位器(BCL)装置的安全性和有效性的对照试验 未触及的浸润性乳腺癌或导管原位癌(DCIS)的研究对象 FDA最近批准的设备豁免(IDE)(2019年11月)。受试者将被随机分配到乳房 保留性手术(BCS)利用BCL或钢丝定位(WL)来指导手术。BCL是一种新的患者- 专为保乳手术(BCS)设计的专用引导装置，用于(I)消除钢丝定位 -对病人和外科医生来说，这是一种效果适中、成本较高、肯定不方便的手术- 同时(Ii)减少正边际比率(PMR)和随后的再次切除手术-a 巨大但不必要的负担不仅给患者带来了负担，也给医疗保健成本带来了负担。在建议的 针对第二阶段的应用，凯恩将(I)支持7个临床站点，作为多中心枢纽随机试验的一部分 对照试验，RCT(在最多15个中心；剩余的支持将来自最近获得的私人支持 投资)在438名受试者(每支手臂219名)中产生证据，证明使用BCL的BCS后的PMR 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 研究生成有关医院和支付者的使用、支出和节省的数据，以支持市场采用， 以及(Iii)向FDA提交关于与WL相关的BCL PMR减少营销索赔的从头分类请求。 基于最近完成的达特茅斯随机前瞻性试验的初步结果 发布了导线本地化的RCT(参见研究策略中的表1)，我们已经估计了WL中的PMR ARM为19%。建议的研究设计允许最终评估BCL的优势，具有强大的 足以检测到有临床意义的PMR下降40%，从19%下降到11.2%。为备战 建议的RCT，在成功完成必要的 在设计控制下的产品开发和测试，包括灭菌验证和生物兼容性 测试。此外，我们还开发了制造工艺，以在监管下制造BCL设备 通过垂直集成设备进行临床试用所需的控制，并实现足够的吞吐量放大 制造、过程检验、杀菌和无尘室包装能力。正保证金比率 与当代BCS相关的BCS很高(~18%-22.3%)，并对患者和 乳房保健的成本。手术切缘对局部复发影响的荟萃分析也证实了 负的利润率对预后有积极的影响。因此，凯恩外科公司处于有利地位，可以开发和 将一种可能改变实践的BCS方法商业化，以改善患者的临床结果。

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.