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）：我，Edward B. Garon，医学博士，是加州大学洛杉矶分校血液学和肿瘤学部的医学助理教授，主要研究肺癌。我的短期目标是接受临床/转化研究方面的培训，完成单用厄洛替尼与厄洛替尼加氟维司群的临床试验，并评估作为该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者发起的试验，并发展成为一名能够成功竞争同行评审资金的独立科学家。 2) 临床——成为胸部肿瘤医学领域的学术领导者，专注于以患者为中心的研究。为了实现这些目标，我设计了一个职业发展计划，其中包括广泛的、高度结构化的指导和教学培训。 加州大学洛杉矶分校 (UCLA) 是世界领先的研究和教学大学之一，在基础科学和临床科学领域开展全方位的研究。加州大学洛杉矶分校琼森综合癌症中心 (JCCC) 成员包括近 300 名医生和科学家。临床试验针对多种恶性肿瘤进行。附属的国际转化肿瘤学研究 (TORI) 网络涵盖 27 个诊所，67 个办公室、154 名医生。 我至少 80% 的时间将用于研究相关活动。我获得了个人办公空间、用于临床呼叫的呼叫中心、医疗助理、护理人员和执业护士 (25%)。我的临床职责仅限于每年 1 个月的住院职责和每周半天的门诊时间。血液学/肿瘤学部主席 Dennis J. Slamon 医学博士、哲学博士在一封信中描述了机构对我的项目和我的职业生涯的承诺。 JCCC 主任朱迪思·加森 (Judith Gasson) 也写了一封信，描述了我可以通过 JCCC 获得的资源。我将获得医学博士史蒂文·M·杜比内特 (Steven M. Dubinett) 的主要指导。杜比内特博士 20 多年来一直是各个级别学员的成功导师。他在肺癌研究方面的成功指导记录包括许多曾获得职业发展奖的初级教师。大多数获奖者都作为独立调查员取得了成功的职业生涯。这些受训者已在本申请中的 Dubinett 博士的受训者名单中注明。 Dubinett 博士在过去十年中领导了 UCLA Lung SPORE 培训项目，也是两项 NIH T32 培训资助的 PI。他曾在 TRWG 培训委员会任职。在颁奖期间，我将每周与杜比内特博士会面。我们会议的主题包括数据审查和实验规划；手稿和提案的准备以及职业建议。我还将每月与我的导师委员会会面，该委员会由 Dennis J. Slamon 医学博士、哲学博士、Robert Elashoff 博士和 Richard J. Pietras 医学博士、哲学博士组成。杜比内特博士也将出席这些会议。此外，我每月都会与我的外部顾问 Jill Siegfried 博士进行电话通话并每年举行三次会议。 我将在一个高度结构化、受保护和刺激的研究环境中致力于肺癌的转化研究。我已报名参加加州大学洛杉矶分校 K30 转化研究研究生培训计划，以获得临床研究理学硕士学位。课程作业的时间安排是为了最有利于我提出的研究计划而定制的。培训计划期间的额外重点将是手稿和资助写作。此外，我还将参加部门和部门的研究会议、每周的实验室会议、临床研究会议和期刊俱乐部。我将继续参加 JCCC 研讨会系列，其中包括每月一次的肺癌研讨会。我的研究计划需要评估雌激素受体 (ER) 通路与表皮生长因子受体 (EGFR) 通路相结合在非小细胞肺癌 (NSCLC) 中的作用。 1) 我将完成厄洛替尼单独使用或与氟维司群联合使用的临床试验。 102 名患有 IIIB 或 IV 期 NSCLC 且至少接受过一种既往治疗（除非患者拒绝其他治疗）的患者将被纳入这项在 UCLA 并通过 TORI 网络进行的 II 期随机临床试验。该项目获得了 UCLA IRB、WIRB（针对 TORI 站点）、UCLA ISPRC 的批准，并获得了 FDA 的 IND 批准。预计 102 名患者中有 51 名已入组。该研究的主要目的是确定每组的反应率。次要目标包括无进展生存期、总体生存期和安全性。 2) 我将评估作为临床试验一部分收集的血液样本的生物标志物，包括雌二醇和研究生物标志物 NGAL 和 MMP-9，以及 3) 我将评估作为临床试验一部分收集的组织的相关次要终点，包括肿瘤ER、ER、黄体酮受体、芳香酶和 EGFR 的水平以及 EGFR 突变和其他选定的生物标志物。 在该项目结束时，我将能够进行研究者发起的临床试验并进行广泛的相关分析。这将通过开展拟议的研究、在该项目过程中接受指导以及通过加州大学洛杉矶分校临床研究理学硕士 (K30) 计划进行教学学习来实现。在本次研究培训结束时，我将成为一名独立的医师科学家，从事以患者为导向的肺癌研究，并且我预计会竞争独立研究经费。