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

项目总结/摘要： CairnSurgical，Inc.，一家达特茅斯的衍生公司，将进行一项前瞻性，多中心，1：1随机， 一项对照试验，旨在评估其乳腺癌切除术（BCL）设备在 接受研究的未触及浸润性乳腺癌或导管原位癌（DCIS）受试者 FDA最近批准的器械豁免（IDE）（2019年11月）。受试者将被随机分配至乳房 保留性手术（BCS），使用BCL或导丝定位（WL）来引导手术。BCL是一种新的病人 设计用于乳房保留手术（BCS）的特定引导器械，以（i）消除导丝定位 - 这是一种适度有效、有点昂贵并且对患者和外科医生来说肯定不方便的手术， 同时（ii）降低切缘阳性率（PMR）和随后的再次切除手术- a 这不仅对患者而且对医疗保健费用造成了重大但不必要的负担。拟议 直接进入II期申请，Cairn将（i）支持7个临床研究中心，作为多中心关键随机 对照试验，RCT（最多15个中心;其余支持将来自最近获得的私人 在438例受试者（每组219例）中进行研究，以证明使用BCL进行BCS后的PMR是 相对于标准治疗（WL）降低，（ii）通过医疗保健经济学评估BCL成本效益 研究生成有关使用、结果和节省的数据，以支持市场采用， 和（iii）向FDA提交重新分类申请，要求BCL PMR相对于WL减少营销声明。 根据最近完成的达特茅斯随机前瞻性试验23的初步结果和几项 已发表的导丝定位RCT（见研究策略中的表1），我们估计了WL中的PMR 手臂为19%。拟定的研究设计允许明确评价BCL的优效性，具有把握度 足以检测到有临床意义的PMR降低40%，从19%降至11.2%。为筹备 CairnSurgical在成功完成必要的临床试验后，已获得FDA的IDE批准。 设计控制下的产品开发和测试，包括灭菌确认和生物相容性 试验.此外，我们还开发了制造工艺，以根据监管要求制造BCL器件。 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吞吐量放大 制造、过程中检验、灭菌和洁净室包装能力。正利润率 与当代BCS相关的高（~18%-22.3%），并对患者造成显著的压力， 乳房保健的费用。关于手术切缘对局部复发影响的荟萃分析也证实， 阴性边缘具有积极的预后作用。因此，CairnSurgical处于有利地位， 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局。

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.