Brain Tumor Clinical and Clinical Research Program (Clinical Support Services)

脑肿瘤临床和临床研究计划（临床支持服务）

• 批准号: 9154383
• 负责人: Mark Gilbert
• 金额: $ 194.81万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9154383
• 关键词: Adult; American Society of Clinical Oncology; Angiogenesis Inhibitors; Antineoplastic Agents; Basic Science; Belief; Biological Response Modifiers; Biology; Biotechnology; Brain; Brain Neoplasms; Cancer Center; Cardiology; Central Nervous System Neoplasms; Characteristics; Child; Clinic; Clinical; Clinical Research; Clinical Trials; Collaborations; Communities; Competence; Complement; Complex; Consultations; Dana-Farber Cancer Institute; Data; Development; Disease; Double-Blind Method; Endocrinology; Ensure; Environment; Fellowship; Freedom; Genetic; Glioblastoma; Glioma; Group Practice; Health; Health system; Healthcare; Hospitals; Immune; Immunologic Monitoring; Individual; Institution; Intramural Research Program; Journals; Kansas; Laboratories; Leadership; Malignant Glioma; Malignant Neoplasms; Measures; Medical; Medical Oncology; Medical center; Medicine; Methodist Church; Mission; Molecular; Monitor; National Cancer Institute; National Heart, Lung, and Blood Institute; National Institute of Mental Health; National Institute of Neurological Disorders and Stroke; Neuraxis; Neurocognitive Deficit; Neurology; Neurosurgeon; New England; Newly Diagnosed; North Carolina; Nurse Practitioners; Nursing Research; Ohio; Oncologic Nursing; Oncologist; Oncology Nurse; Ophthalmology; Outcome; Pain; Pathology; Patient Care; Patients; Peripheral Blood Mononuclear Cell; Pharmacologic Substance; Phase; Phase II/III Trial; Physical Medicine; Physicians; Placebo Control; Primary Brain Neoplasms; Psychiatry; Publishing; Quality of life; Radiation Oncologist; Radiation Oncology; Radiation Therapy Oncology Group; Randomized; Research; Research Infrastructure; Research Personnel; Research Project Grants; Resources; Role; Running; Second Opinions; Services; Site; Social Work; South Carolina; Specialist; Specimen; Spinal Cord Neoplasms; Stratification; Symptoms; Testing; Texas; Therapeutic; Therapeutic Agents; Tissues; Training; Training Programs; Translational Research; Treatment Efficacy; Tumor Biology; Tumor Tissue; United States National Institutes of Health; Universities; Utah; Washington; Work; anticancer research; arm; base; bevacizumab; cancer care; clinical care; clinical investigation; cognitive function; collaborative trial; design; drug development; effective therapy; improved; inhibitor/antagonist; innovation; medical schools; member; multidisciplinary; neuro-oncology; neurosurgery; novel; novel diagnostics; novel therapeutics; oncology; oncology service; palliation; personalized medicine; phase II trial; phase III trial; programs; prototype; research study; safety testing; standard care; tool; tumor; tumor immunology

The NOB has made substantial progress towards building an infrastructure necessary for fulfilling its mission of developing new and improved therapies for children and adults with brain and spinal cord tumors. When Dr. Gilbert came to the NIH in November 2014, he has rebuilt the Brain Tumor Clinical and Clinical Research Program: a highly collaborative, robust translational research program centered on finding treatments for brain and other central nervous system tumors. In addition to conducting basic and translational research, the NOB has become a nationally recognized resource for patient information and referrals for second opinions. In addition to seeing and treating brain tumor patients, Dr. Gilbert currently runs a significant number of national clinical trials and helps organize and administrate over several large national Neuro-Oncology translational science initiatives. Most recently, Dr. Gilbert led RTOG 0825 which evaluated the role of the anti-angiogenic agent, bevacizumab, in patients with newly diagnosed glioblastoma in a double-blind placebo controlled randomized phase III trial. This study accrued 973 patients and successfully incorporated upfront stratification by two molecular parameters, as there was 100% compliance with tumor tissue submission. This study, which did not demonstrate a surivival benefit for bevacizumab, demonstrated neurocognitive decline and worsened symptom burden and quality of life in the patients treated with bevacizumab. This study was presented at the Plenary Session at ASCO and published in the New England Journal of Medicine. These efforts have led to my leadership of NRG BN002, a clinical trial that is testing the safety of adding the immune checkpoint inhibitors, ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) in patients with newly diagnosed glioblastoma. This is the prelude to an anticipated 4-arm randomized, placebo-controlled phase II trial that will pick the best experiment arm (ipilimumab, nivolumab or the combination) to test in a phase III placebo controlled registration trial. A critical component of the phase II and phase III trial will be the immunologic monitoring which will comprise testing of tumor tissue for mediators of immune-reactivity and serial monitoring of peripheral blood mononuclear cells as an indicator of the impact of treatment on "immune competence". This work will be done in the Neuro-Oncology Branch Laboratory in close collaboration with the Laboratory of Tumor Immunology and Biology led by Dr. Jeffrey Schlom, with direct collaboration with Dr. Christopher Heery. Dr. Gilbert has also transitioned the Brain Tumor Trials Collaborative from M. D. Anderson Cancer Center. This is a national consortium that was founded on philanthropic support. The mission of the BTTC is to rapidly develop and complete innovative clinical trials for patients with primary brain tumors. To date, the BTTC has completed a study that used a factorial design (8 treatment arms were evaluated simultaneously) and a trial that used an adaptive randomized design (patient allocation based on treatment efficacy using patient by patient rebalancing). This effort is currently being transferred from the M. D. Anderson Cancer Center to the NCI. There are currently 3 active studies and once re-launched, addition study concepts are anticipated. The list of participating sites is provided below: Aurora Advanced Healthcare National Institutes of Health Baylor University Northwestern University, Feinberg School of Medicine Case Western Reserve SOM Ohio State University Cedar-Sinai Medical Center Rush University Cancer Center Cleveland Clinic Texas Oncology Columbia University The Methodist Hospital Dana Farber Cancer Institute University of North Carolina Henry Ford Health System University of Kansas Medical University of South Carolina University of Utah Orlando Health University of Washington Mayo Clinic UT M. D. Anderson Cancer Center Northshore University Health System UT Southwestern Medical Center at Dallas The NOB has created a vibrant, robust and clinically busy center for neuro-oncology excellence that serves as a national resource for patients with CNS malignancies (regardless of their ability to pay), for information, consultation, clinical trials or referrals to their local centers of excellence for clinical care and NCI-sponsored trials. This was an important accomplishment because: Part of the mission of the NCI should be to provide expertise to patients and physicians for a lethal tumor type not frequently seen in the community and for whom standard treatment options are limited. A busy and robust clinical program ensures a steady flow of patients with primary CNS tumors imperative for stimulating clinical and translational research by ensuring rapid patient accrual to clinical trials, efficient acquisition of tissue for basic and translational research, and for enticing pharmaceutical/biotechnology companies to co-develop novel CNS tumor agents with the NOB and the NCI at large. A multi-disciplinary tumor board convenes every other week and is attended by neuro-oncologists, radiation oncologists, neurosurgeons, neuropathologists and laboratory investigators. Complex and challenging patients are presented and discussed, optimizing individual patient care and leading to many collaborative interactions and research projects. This Tumor Board is complemented by a bi-weekly pathology review where NIH neuropathologists prepare specimens from active clinical patients that are examined microscopically and morphologic and genetic features are discussed in conjunction with members of the Brain Tumor Clinical Team. Additionally, a Molecular Tumor Board is under development that will compile all of the available molecular information from individual patient's tumors so that therapies can be considered in the context of this information. Below are partial lists of accomplishments in the building of an NIH-wide multidisciplinary Brain Tumor Clinic with active participation from three different NCI Branches (ROB, MOCRU, CCRLP), six different NIH Institutions (NCI, NINDS, NEI, NHLBI, NIMH), and five different Clinical Center Programs (Neuroradiology, Psychiatry, Pain and Palliation, Rehabilitation Medicine, Social Work). Expertise represented in the clinic includes Medical Oncology, Radiation Oncology, Neurosurgery, Neurology, Ophthalmology, Cardiology, Psychiatry, Endocrinology, Social Work, and Rehabilitation Medicine; Assembled a primary neuro-oncology clinical care/research team, which now consists of 4 neuro-oncologists, 4 NOB-trained neuro-oncology nurse practitioners, 2 research nurses, 1 neuro-oncology fellow, 2 patient coordinators, 2 clinical trials specialists and 2 data managers; Additionally, the NOB provides neuro-oncology services for Walter Reed Medical Center, in Bethesda; established close collaborative clinical programs with Johns Hopkins Medical Center, George Washington Medical Center, Fairfax Inova and Washington Hospital Center and a wide array of private neurosurgical, radiation, and oncology practice groups locally and nationally; created a neuro-oncology fellowship training program between the NIH and the Johns Hopkins Medical Center.

NOB 在建设必要的基础设施方面取得了实质性进展，以履行其为患有脑部和脊髓肿瘤的儿童和成人开发新的和改进的疗法的使命。当 Gilbert 博士于 2014 年 11 月来到 NIH 时，他重建了脑肿瘤临床和临床研究计划：一个高度协作、稳健的转化研究计划，致力于寻找脑肿瘤和其他中枢神经系统肿瘤的治疗方法。除了进行基础研究和转化研究外，NOB 还成为全国公认的患者信息和第二意见转诊资源。除了看诊和治疗脑肿瘤患者外，吉尔伯特博士目前还开展了大量的国家临床试验，并帮助组织和管理多项大型国家神经肿瘤转化科学计划。最近，Gilbert 博士领导了 RTOG 0825，该项目在一项双盲安慰剂对照随机 III 期试验中评估了抗血管生成药物贝伐单抗在新诊断的胶质母细胞瘤患者中的作用。这项研究招募了 973 名患者，并成功地通过两个分子参数进行了前期分层，因为肿瘤组织提交的合规性为 100%。这项研究没有证明贝伐珠单抗对生存有益处，但表明接受贝伐珠单抗治疗的患者神经认知能力下降，症状负担和生活质量恶化。这项研究在 ASCO 全体会议上发表，并发表在《新英格兰医学杂志》上。这些努力促使我领导了 NRG BN002，这是一项临床试验，旨在测试在新诊断的胶质母细胞瘤患者中添加免疫检查点抑制剂 ipilimumab（抗 CTLA-4）和 nivolumab（抗 PD-1）的安全性。这是预期的 4 组随机、安慰剂对照 II 期试验的前奏，该试验将选择最佳实验组（伊匹单抗、纳武单抗或组合）在 III 期安慰剂对照注册试验中进行测试。 II 期和 III 期试验的一个关键组成部分将是免疫监测，其中包括检测肿瘤组织中的免疫反应介质，以及连续监测外周血单核细胞，作为治疗对“免疫能力”影响的指标。 。这项工作将在神经肿瘤学分支实验室与 Jeffrey Schlom 博士领导的肿瘤免疫学和生物学实验室密切合作，并与 Christopher Heery 博士直接合作进行。吉尔伯特博士还从 MD 安德森癌症中心移交了脑肿瘤试验合作组织。这是一个在慈善支持下成立的国家财团。 BTTC 的使命是快速开发并完成针对原发性脑肿瘤患者的创新临床试验。迄今为止，BTTC 已完成一项使用析因设计的研究（同时评估 8 个治疗组）和一项使用适应性随机设计的试验（使用逐个患者重新平衡，根据治疗效果进行患者分配）。这项工作目前正从 M.D. 安德森癌症中心转移到 NCI。目前有 3 项正在进行的研究，一旦重新启动，预计还会有更多的研究概念。参与地点列表如下： Aurora Advanced Healthcare 美国国立卫生研究院 贝勒大学 西北大学 Feinberg 医学院 Case Western Reserve SOM 俄亥俄州立大学 Cedar-Sinai 医疗中心 拉什大学癌症中心 克利夫兰诊所 德克萨斯肿瘤学 哥伦比亚大学 卫理公会医院达纳法伯癌症研究所 北卡罗来纳大学 亨利福特健康系统 堪萨斯大学医科大学 南卡罗来纳大学 犹他大学 奥兰多健康中心 华盛顿大学梅奥诊所 德克萨斯大学医学博士安德森癌症中心 北岸大学健康系统 达拉斯 UT 西南医学中心 NOB 创建了一个充满活力、稳健且临床繁忙的神经肿瘤学卓越中心，为中枢神经系统恶性肿瘤患者（无论其支付能力如何）提供信息和咨询服务、临床试验或转介至当地卓越中心进行临床护理和 NCI 赞助的试验。这是一项重要的成就，因为： NCI 的部分使命应该是为社区中不常见且标准治疗选择有限的致命肿瘤类型的患者和医生提供专业知识。繁忙而强大的临床计划可确保原发性中枢神经系统肿瘤患者的稳定流动，这对于刺激临床和转化研究至关重要，确保患者快速进入临床试验，有效获取用于基础和转化研究的组织，并吸引制药/生物技术公司与 NOB 和 NCI 共同开发新型 CNS 肿瘤药物。多学科肿瘤委员会每隔一周召开一次会议，出席人员包括神经肿瘤学家、放射肿瘤学家、神经外科医生、神经病理学家和实验室研究人员。复杂和具有挑战性的患者被呈现和讨论，优化个体患者护理并导致许多协作互动和研究项目。该肿瘤委员会辅以每两周一次的病理学审查，其中 NIH 神经病理学家从活跃的临床患者中制备标本，进行显微镜检查，并与脑肿瘤临床团队的成员一起讨论形态和遗传特征。此外，分子肿瘤委员会正在开发中，它将编译来自个体患者肿瘤的所有可用分子信息，以便可以根据这些信息考虑治疗方法。以下是在 NIH 范围内的多学科脑肿瘤诊所建设中取得的部分成就列表，其中包括三个不同的 NCI 分支机构（ROB、MOCRU、CCRLP）、六个不同的 NIH 机构（NCI、NINDS、NEI、NHLBI、NIMH）的积极参与，以及五个不同的临床中心项目（神经放射学、精神病学、疼痛与姑息治疗、康复医学、社会工作）。诊所的专业知识包括肿瘤内科、放射肿瘤学、神经外科、神经病学、眼科、心脏病学、精神病学、内分泌学、社会工作和康复医学；组建了一个初级神经肿瘤学临床护理/研究团队，目前由 4 名神经肿瘤学家、4 名经过 NOB 培训的神经肿瘤科执业护士、2 名研究护士、1 名神经肿瘤学研究员、2 名患者协调员、2 名临床试验专家和2名数据管理员；此外，NOB 还为贝塞斯达的沃尔特·里德医疗中心提供神经肿瘤学服务；与约翰霍普金斯医疗中心、乔治华盛顿医疗中心、费尔法克斯伊诺瓦和华盛顿医院中心以及当地和全国范围内的众多私人神经外科、放射和肿瘤学实践小组建立了密切的合作临床项目；美国国立卫生研究院和约翰·霍普金斯医学中心之间创建了一个神经肿瘤学奖学金培训计划。