Inhibiting EGFR and ER pathways in NSCLC

抑制 NSCLC 中的 EGFR 和 ER 通路

• 批准号: 8302279
• 负责人: EDWARD B GARON
• 金额: $ 16.52万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-15 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8302279
• 关键词: Antiestrogen Therapy; Area; Aromatase; Award; Basic Science; Biological Assay; Biological Markers; Biological Markers; Blood; Blood specimen; Breast; California; Cancer Etiology; Cancer Patient; Cessation of life; Chairperson; Chest; Clinic; Clinical; Clinical Data; Clinical Research; Clinical Research Curriculum Award; Clinical Sciences; Clinical Trials; Cohort Studies; Combined Modality Therapy; Comprehensive Cancer Center; Conduct Clinical Trials; Data; Databases; Development Plans; Disease; Doctor of Medicine; Doctor of Philosophy; Educational process of instructing; Enrollment; Environment; Epidermal Growth Factor Receptor; Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor; Erlotinib; Estradiol; Estrogen Antagonists; Estrogen Receptor Modulators; Estrogen Receptors; Estrogens; Etiology; European; Evaluation; Faculty; Fulvestrant; Funding; Gelatinase B; Goals; Grant; Growth; Growth Factor; Hematology; In Vitro; Incidence; Inpatients; Institutional Review Boards; International; Investigation; Jonsson Comprehensive Cancer Center of University of California Los Angeles; Journals; K-Series Research Career Programs; Laboratories; Lead; Learning; Letters; Los Angeles; Lung; Malignant Neoplasms; Malignant neoplasm of lung; Manuscripts; Master of Science; Medical; Medical Oncology; Medicine; Mentors; Mentorship; Mutation; Non-Small-Cell Lung Carcinoma; Nurse Practitioners; Nursing Staff; Outcome; Pathway interactions; Patients; Peer Review; Phase; Phase II Clinical Trials; Physicians; Play; Positioning Attribute; Preparation; Progesterone; Progesterone Receptors; Progestins; Prognostic Marker; Progression-Free Survivals; Public Health; Randomized; Randomized Clinical Trials; Relative (related person); Replacement Therapy; Research; Research Personnel; Research Proposals; Research Training; Resistance; Resources; Risk; Role; Safety; Sampling; Scientist; Series; Signal Pathway; Signal Transduction; Site; Specimen; Staging; Structure; Subgroup; Telephone; Time; Tissue Sample; Tissues; Training; Training Programs; Translational Research; United States; United States National Institutes of Health; Universities; Woman; Work; Writing; anticancer research; arm; base; cancer research center director; carcinogenesis; career; career development; cigarette smoking; design; enzyme biosynthesis; improved; in vivo Model; inhibitor/antagonist; meetings; member; men; mortality; oncology; patient oriented; patient oriented research; pre-clinical; professor; prospective; research study; response; symposium; trial comparing; tumor

DESCRIPTION (provided by applicant): I, Edward B. Garon, M.D., am an Assistant Professor of Medicine in the Division of Hematology and Oncology at UCLA with a focus in lung cancer. My short term goals are to receive training in the conduct of clinical/translational research, to complete a clinical trial of erlotinib alone vs. erlotinib plus fulvestrant, and to evaluate clinical and correlative data generated as part of this trial. My career goals are: 1) Research- To develop investigator-initiated trials based on my laboratory work and develop into an independent scientist who can successfully compete for peer-reviewed funding. 2) Clinical- To become an academic leader in thoracic medical oncology, focused on patient-oriented research. In order to achieve these goals, I have designed a career development plan that includes extensive, highly structured mentorship and didactic training. The University of California, Los Angeles (UCLA) is one of the world's leading research and teaching universities, conducting a full spectrum of research in basic and clinical science. The UCLA Jonsson Comprehensive Cancer Center (JCCC) members include nearly 300 physicians and scientists. Clinical trials are conducted across a wide range of malignancies. The affiliated Translational Oncology Research International (TORI) Network encompasses 27 practices with 154 physicians in 67 offices. At least 80% of my overall time will be devoted to research related activities. I have been provided with personal office space, access to a call center for clinical calls, medical assistants, nursing staff, and a nurse practitioner (25%). My clinical responsibilities will be limited to 1 month of inpatient responsibility per year and one half-day of clinic per week. The institutional commitment to my project and my career are described in a letter from Dennis J. Slamon, M.D., Ph.D., chairman of the Division of Hematology/Oncology. Judith Gasson, JCCC director, has also written a letter describing resources that will be available to me through the JCCC. I will receive primary mentorship from Steven M. Dubinett, M.D. Dr. Dubinett been a successful mentor for trainees at all levels for more than 20 years. His successful track record of mentorship in lung cancer research includes numerous junior faculty who have been career development award recipients. The majority of these awardees have gone on to successful careers as independent investigators. These trainees are noted in Dr. Dubinett's trainee list in this application. Dr. Dubinett has lead the UCLA Lung SPORE training program for the past ten years and is also the PI for two NIH T32 training grants. He served on the training committee for the TRWG. I will meet weekly with Dr. Dubinett during the award period. Topics covered in our meetings will include review of data and planning of experiments; manuscript and proposal preparation and career advice. I will also meet monthly with my Mentorship Committee consisting of Dennis J. Slamon, M.D., Ph.D., Robert Elashoff, Ph.D., and Richard J. Pietras M.D., Ph.D. Dr. Dubinett will also attend these meetings. In addition, I will have monthly phone calls and thrice yearly meetings with my external advisor, Jill Siegfried, Ph.D. I will be in a highly structured, protected and stimulating research environment devoted to translational research in lung cancer. I have enrolled in the UCLA K30 Graduate Training Program in Translational Investigation to receive a Master of Science Degree in Clinical Research. Timing of the coursework has been tailored in order to optimally benefit my proposed research plan. Additional focus during the training program will be directed to manuscript and grant writing. In addition, I will attend departmental and divisional research conferences, weekly laboratory meetings, clinical research meetings, and journal clubs. I will continue to attend the JCCC seminar series which includes a monthly seminar focused on lung cancer. My research proposal entails evaluation of the role of the estrogen receptor (ER) pathway in combination with the epidermal growth factor receptor (EGFR) pathway in non-small cell lung cancer (NSCLC). 1) I will complete a clinical trial of erlotinib alone or in combination with fulvestrant. 102 Patients with Stage IIIB or IV NSCLC and at least one prior line of therapy (unless patient refuses other therapy) will be enrolled on this phase II, randomized clinical trial conducted at UCLA and through the TORI Network. The project received approval from the UCLA IRB, WIRB (for TORI sites), UCLA ISPRC, and it received IND approval from the FDA. 51 of the projected 102 patients have been enrolled. The primary objective of the study is to determine the response rate in each arm. Secondary objectives include progression-free survival, overall survival and safety. 2) I will evaluate blood samples collected as part of the clinical trial for biologic markers, including estradiol and investigational biomarkers NGAL and MMP-9, and 3) I will evaluate tissue collected as part of the clinical trial for correlative secondary endpoints, including tumor levels of ER, ER, progesterone receptor, aromatase and EGFR as well as EGFR mutations and other selected biologic markers. At the conclusion of this project, I will be able to conduct investigator-initiated clinical trials with extensive correlative analysis. This will be accomplished by conducting the proposed research, receiving mentorship during the course of this project, and didactic learning through the UCLA Masters of Science in Clinical Research (K30) Program. At the conclusion of this research training, I will be well positioned to function as an independent physician scientist in patient-oriented lung cancer research, and I anticipate competing for independent research funding.

描述（由申请人提供）：I，Edward B. Garon，医学博士，是加州大学洛杉矶分校血液学和肿瘤科医学助理教授，重点是肺癌。我的短期目标是接受进行临床/转化研究的培训，以完成单独的erlotinib vs. Erlotinib Plus Fulvestrant的临床试验，并评估本试验的一部分生成的临床和相关数据。我的职业目标是：1）研究 - 根据我的实验室工作开发研究人员发起的试验，并发展成为一个独立的科学家，他们可以成功竞争同行评审的资金。 2）临床 - 成为胸腔医学肿瘤学的学术领导者，重点是以患者为导向的研究。为了实现这些目标，我设计了一项职业发展计划，其中包括广泛的，高度结构化的指导和教学培训。 加利福尼亚大学洛杉矶分校（加州大学洛杉矶分校）是世界领先的研究和教学大学之一，在基础和临床科学领域进行了全面研究。 UCLA Jonsson综合癌症中心（JCCC）成员包括近300名医生和科学家。临床试验是在广泛的恶性肿瘤中进行的。附属的翻译肿瘤研究国际（TORI）网络包括67个办事处的154位医生，包括27种实践。 我的整个时间的至少80％将专门用于研究相关的活动。为我提供了个人办公空间，访问临床电话的呼叫中心，医疗助理，护理人员和护士从业人员（25％）。我的临床责任将限制为每年住院责任1个月，每周半天的诊所。血液学/肿瘤学系主任Dennis J. Slamon，M.D。，博士学位丹尼斯·J·斯拉蒙（Dennis J. JCCC董事朱迪思·加森（Judith Gasson）还写了一封信，描述了通过JCCC可用的资源。我将获得医学博士史蒂文·杜比尼特（Steven M.他在肺癌研究中成功的指导记录包括众多曾是职业发展奖获得者的初级教师。这些获奖者中的大多数已成为独立调查员的成功职业。这些学员在此应用程序中的杜比尼特（Dubinett）学员名单中被指出。杜比尼特（Dubinett）博士在过去的十年中领导了UCLA肺孢子训练计划，也是两项NIH T32培训补助金的PI。他曾在TRWG培训委员会任职。在颁奖期间，我将每周与杜比尼特博士见面。会议中涵盖的主题将包括审查数据和实验计划；手稿和建议准备和职业建议。我还将每月与我的指导委员会会面，由M.D. Dennis J. Slamon，博士，Robert Elashoff博士和Richard J. Pietras M.D.杜比尼特博士还将参加这些会议。此外，我将每月与我的外部顾问Jill Siegfried，Ph.D. 我将处于一个高度结构化的，受保护和刺激的研究环境中，该研究环境致力于肺癌的转化研究。我已经参加了UCLA K30研究生培训计划的转化研究，以获得临床研究硕士学位。为了最佳地使我提出的研究计划受益，该课程的时机是为了最佳造福而量身定制的。培训计划期间的其他重点将指向手稿和赠款写作。此外，我将参加部门和部门研究会议，每周实验室会议，临床研究会议和期刊俱乐部。我将继续参加JCCC研讨会系列，其中包括针对肺癌的每月一次研讨会。我的研究建议需要评估非小细胞肺癌（NSCLC）中雌激素受体（ER）途径与表皮生长因子受体（EGFR）途径结合的作用。 1）我将单独或与Fulvestrant结合完成厄洛替尼的临床试验。 102例IIIB或IV期NSCLC患者以及至少一项先前的治疗（除非患者拒绝其他疗法）将参加此II期，这是在UCLA和TORI网络进行的随机临床试验。该项目获得了UCLA IRB，WIRB（用于Tori网站），UCLA ISPRC的批准，并获得了FDA的IND批准。预计的102名患者中有51名已入学。该研究的主要目的是确定每个手臂的响应率。次要目标包括无进展的生存，整体生存和安全性。 2）我将评估作为生物学标志物的临床试验的一部分收集的血液样本，包括雌二醇和研究性生物标志物NGAL和MMP-9，以及3）我将评估作为相关次要端点的临床试验收集的组织，包括ER，ER，ER，ER，ER，ER，ER，ER，BISTERSONOR，BIOMETSOR，ARAMTOSE，AROMATES和EGFR的肿瘤水平以及EGFR，以及EGFR的其他以及EGFR，以及其他。 在该项目的结论中，我将能够进行研究人员发射的临床试验，并进行广泛的相关分析。这将通过进行拟议的研究，在本项目的过程中获得指导以及通过UCLA临床研究科学硕士（K30）计划来实现。在这项研究培训的结论中，我将有能力成为以患者为导向的肺癌研究的独立医师科学家，我预计我预计会争夺独立的研究资金。