Brain Tumor Clinical and Clinical Research Program

脑肿瘤临床和临床研究计划

• 批准号: 10262806
• 负责人: Mark Gilbert
• 金额: $ 187.05万
• 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/10262806
• 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; Communities; Complement; Complex; Consultations; Dana-Farber Cancer Institute; Disease; Doctor of Medicine; Double-Blind Method; Endocrinology; Ensure; Environment; Fellowship; Freedom; Genetic; Glioblastoma; Glioma; Group Practice; Health; Health system; Healthcare; Hospitals; Immune checkpoint inhibitor; Immune response; Immunocompetence; Immunologic Monitoring; Infrastructure; Institution; Intramural Research Program; Journals; Kansas; Laboratories; Leadership; Malignant Glioma; Malignant Neoplasms; Measures; Medical; Medical Oncology; Medical center; Medicine; Methodist Church; Microscopic; Mission; Molecular; Monitor; Morphology; 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; Nivolumab; North Carolina; Nurse Practitioners; Nursing Research; Ohio; Oncologist; Oncology; Ophthalmology; Pain; Pathology; Patient Agents; Patient Care; Patient-Focused Outcomes; Patients; Peripheral; Peripheral Blood Mononuclear Cell; Pharmacologic Substance; Physical Medicine; Physicians; Placebos; Primary Brain Neoplasms; Privatization; Psychiatry; Publishing; Quality of life; Radiation Oncologist; Radiation Oncology; Radiation Therapy Oncology Group; Randomized; Research; Research Personnel; Research Project Grants; Resources; Role; Running; Second Opinions; Site; Social Work; South Carolina; Specialist; Specimen; Spinal Cord Neoplasms; Stratification; Symptoms; Testing; Texas; Therapeutic; Tissues; Training Programs; Translational Research; Treatment Efficacy; Tumor Tissue; United States National Institutes of Health; Universities; Utah; Washington; anti-CTLA4; anti-PD-1; anticancer research; base; bevacizumab; cancer care; clinical care; clinical center; clinical investigation; cognitive function; collaborative trial; design; drug development; effective therapy; improved; individual patient; individualized medicine; innovation; medical schools; member; multidisciplinary; neuro-oncology; neurosurgery; novel; novel diagnostics; novel therapeutics; oncology service; palliation; personalized medicine; phase III trial; programs; prototype; safety testing; standard care; survival outcome; tool; translational research program; treatment arm; tumor

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. Since Dr. Gilbert's arrival at 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. Importantly, 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 survival 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 his 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 NOB study that will help determine whether these immune checkpoint inhibitors have efficacy in glioblastoma by determining if patients who demonstrate a peripheral immune response have improved survival outcomes. A critical component of the 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". Dr. Gilbert has also transitioned the Brain Tumor Trials Collaborative (BTTC) 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 relaunched, and 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 is 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 has been incorporated into the Pathology Review that reviews 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), five different NIH Institutions (NCI, NINDS, NEI, NHLBI, NIMH), and six 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 6 neuro-oncologists, 4 nurse practitioners, 5 research nurses, 5 neuro-oncology fellows, 1 clinical collaborator, 3 patient coordinators, 4 clinical trials specialists; 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. Since the Brain Tumor Clinical and Clinical Research Program re-initiated in 2015, the NOB launched 18 clinical trials.

NOB在建立一个基础设施方面取得了重大进展，以实现其为患有脑和脊髓肿瘤的儿童和成人开发新的和改进疗法的使命。自吉尔伯特（Gilbert）博士于2014年11月到达NIH以来，他重建了脑肿瘤临床和临床研究计划：一项高度协作，可靠的转化研究计划，其重点是寻找针对大脑和其他中枢神经系统肿瘤的治疗方法。除了进行基础和转化研究外，NOB还成为全国认可的患者信息的资源，并引用了第二意见的转诊。除了看和治疗脑肿瘤患者外，吉尔伯特博士目前还进行了大量的国家临床试验，并有助于组织和管理几个大型国家神经肿瘤学转化科学倡议。重要的是，吉尔伯特（Gilbert）博士领导了RTOG 0825，评估了抗血管生成剂贝伐单抗在新诊断的胶质母细胞瘤患者中在一项双盲安慰剂控制的随机III期试验中的作用。这项研究累积了973例患者，并通过两个分子参数成功地纳入了前期分层，因为符合肿瘤组织提及的100％遵守。这项研究并未证明贝伐单抗具有生存益处，表现出神经认知能力下降，并使贝伐单抗治疗的患者的症状负担和生活质量恶化。这项研究是在ASCO的全体会议上发表的，并在《新英格兰医学杂志》上发表。这些努力导致了他领导NRG BN002，这是一项临床试验，正在测试添加免疫检查点抑制剂，ipilimumab（抗CTLA-4）和Nivolumab（抗PD-1）的安全性，以对新诊断的胶质母细胞瘤的患者进行。这是一项NOB研究的前奏，该研究将有助于确定这些免疫检查点抑制剂是否通过确定证明外周免疫反应的患者是否有改善生存结果来对胶质母细胞瘤具有功效。该试验的一个关键组成部分是免疫监测，它将包括对肿瘤组织进行免疫反应性和外周血单单核细胞的序列监测的测试，以此作为治疗对“免疫能力”的影响的指标。吉尔伯特（Gilbert）博士还从M. D. Anderson癌症中心（M. D. Anderson）中心转移了脑肿瘤试验协作（BTTC）。这是一个以慈善支持为基础的国家财团。 BTTC的任务是为原发性脑肿瘤患者快速开发和完整的创新临床试验。迄今为止，BTTC已经完成了一项研究，该研究使用了阶乘设计（同时评估了8个治疗臂）和一项使用自适应随机设计的试验（使用患者重新平衡患者使用患者使用患者进行治疗疗效，患者分配了患者）。目前，这项工作正在从M. D. Anderson癌症中心转移到NCI。目前有3项活跃研究，一旦重新推出，预计会有增加的研究概念。下面提供了参与站点的列表：Aurora Advanced Healthcare，美国国立卫生研究院，贝勒大学，西北大学，Feinberg医学院，Feinberg医学院，Case Western Reserve SOM，俄亥俄州立大学，CEDAR-SINAI医学中心，Rush University Center，Rush University Center，Cleveland Clinic，Cleveland Clinic，德克萨斯州哥伦比亚大学，哥伦比亚大学，卫生部，卫生部，卫生部，卫生部。堪萨斯州，南卡罗来纳州医科大学，犹他大学，奥兰多健康，华盛顿大学，梅奥诊所，UT M. D.安德森癌症中心，北岸大学卫生系统，UT西南医学中心。 NOB创造了一个充满活力，健壮且临床繁忙的神经肿瘤学中心，可作为中枢神经系统恶性肿瘤患者（无论他们的付款能力如何），以获取信息，咨询，临床试验或转介到本地临床护理中心和NCI参议员的卓越中心。这是一项重要的成就，因为：NCI的一部分是为患者和医生提供致命肿瘤类型的专业知识，在社区中不经常见到，并且标准治疗方案有限。忙碌而健壮的临床计划可确保原发性中枢神经系统肿瘤的稳定流动，通过确保快速患者应对临床试验，有效地获取组织进行基础和转化研究，并诱使制药/生物技术公司与Nobe Noge n Novel Noge CNS Tumor Agents与NCI共同开发，从而刺激临床和转化研究。一个多学科的肿瘤委员会每隔一周召集一次，神经肿瘤学家，辐射肿瘤学家，神经外科医生，神经病理学家和实验室研究人员参加。提出和讨论复杂而充满挑战的患者，优化了个体的患者护理，并导致许多协作互动和研究项目。该肿瘤板补充了每两周一次的病理综述，其中NIH神经病理学家准备了从活跃临床患者的标本中，这些标本在显微镜下检查，形态学和遗传特征与脑肿瘤临床团队的成员一起讨论。此外，已经将分子肿瘤板纳入了病理综述中，该综述回顾了各个患者肿瘤的所有可用分子信息，因此可以在此信息的背景下考虑疗法。 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), five different NIH Institutions (NCI, NINDS, NEI, NHLBI, NIMH), and six different Clinical Center Programs (Neuroradiology, Psychiatry, Pain and Palliation, Rehabilitation Medicine, Social 工作）。该诊所代表的专业知识包括医学肿瘤学，辐射肿瘤学，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；组装了一名主要的神经肿瘤学临床护理/研究团队，该团队现在由6位神经肿瘤学家，4名护士从业人员，5名研究护士，5名神经肿瘤研究员，1名临床合作者，3名患者协调员，4位临床试验专家；此外，NOB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·霍普金斯医学中心，乔治·华盛顿医疗中心，费尔法克斯·诺瓦和华盛顿医院中心建立了密切合作的临床计划，以及各种私人神经外科，辐射，辐射和肿瘤学实践在当地和全国范围内；在NIH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。由于脑肿瘤临床和临床研究计划于2015年重新开设，因此NOB启动了18次临床试验。