Novel systemic therapy to improve clinical outcome in small cell lung cancer

改善小细胞肺癌临床结果的新型全身疗法

• 批准号: 8718782
• 负责人: Taofeek K Owonikoko
• 金额: $ 16.29万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-26 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8718782
• 关键词: Address; Antineoplastic Agents; Applications Grants; Arsenic Trioxide; Award; Biological; Biology; Cancer Biology; Cancer Center; Cancer Patient; Chest; Cisplatin; Clinical; Clinical Investigator; Clinical Research; Clinical Trials; Clinical Trials Cooperative Group; Clinical Trials Design; Collaborations; Conduct Clinical Trials; Cytotoxic agent; DNA Damage; DNA Repair; Development; Development Plans; Diagnosis; Differentiation Inducer; Disease; Doctor of Philosophy; Eastern Cooperative Oncology Group; Educational Curriculum; Enrollment; Ensure; Environment; Ethics; Etoposide; Excision; Extensive Stage; Fine needle aspiration biopsy; Funding; Future; Goals; Growth; Hematology; Home environment; Immunodeficient Mouse; In Vitro; Industry; Institutes; Institution; Knowledge; Laboratories; Lead; Leadership; Learning; Malignant Neoplasms; Malignant neoplasm of lung; Manufacturer Name; Master of Science; Medical Oncology; Mentors; Mentorship; Multicenter Trials; NCI-Designated Cancer Center; Neoplasm Transplantation; Newly Diagnosed; Newly Diagnosed Disease; Operative Surgical Procedures; Outcome; Participant; Patients; Pharmaceutical Preparations; Phase II Clinical Trials; Placebos; Preparation; Progression-Free Survivals; Randomized; Recurrent disease; Refractory; Regimen; Regulation; Relapse; Research; Research Design; Research Personnel; Resistance; Resources; Role; Salvage Therapy; Sampling; Scientist; Secure; Source; Staging; Structure; Survival Rate; Systemic Therapy; Techniques; Testing; The Sun; Therapeutic; Therapeutic Agents; Tissue Sample; Toxic effect; Training; Training Programs; Translating; Translational Research; Translations; Tumor Bank; Tumor Biology; Universities; Vision; Work; Xenograft procedure; base; cancer therapy; career; career development; chemotherapy; clinical care; clinical efficacy; cytotoxic; design; didactic education; disorder control; drug testing; effective therapy; experience; human FRAP1 protein; improved; inhibitor/antagonist; interest; lung small cell carcinoma; mortality; novel; novel therapeutic intervention; patient oriented research; patient population; pre-clinical; preclinical evaluation; professor; programs; repair enzyme; research and development; response; tumor

DESCRIPTION (provided by applicant): This candidate is an Assistant Professor in Hematology and Medical Oncology at Emory University. His long- term career goal is to become established as an independent translational researcher with recognized superior expertise in clinical care of lung cancer patients, conduct of clinical trials leading to the development of new treatment options for small cell lung cancer (SCLC) and in the preclinical evaluation of novel compounds likely to develop into effective therapy for SCLC. The candidate is interested in advancing the care and clinical outcome of SCLC patients by investigating new treatment options and developing effective strategies to improve on the efficacy of currently available therapies. The candidate has proposed a career development plan that includes a multi-faceted training and mentoring program designed to provide an intense, patient- oriented research experience. These goals will be achieved through his lead role in the design and conduct of two clinical trials enrolling SCLC patients. The first trial is a single institution study designed by he candidate that will evaluate the clinical efficacy of arsenic trioxide in relapsed disease. If successful, this clinical trial will introduce a novel therapy into the treatment options for the refractory patient population. The second clinical trial is a direct translation of the candidate's preclinical laboratory work designed to evaluate whether the addition of ABT-888, an orally administered PARP inhibitor, will enhance the efficacy of standard chemotherapy agents without increased toxicity in newly diagnosed SCLC patients. This study is planned as a multi-institution clinical trial to be conducted through the established cooperative group mechanism of ECOG. Additionally, in preparation for a long term career as a translational scientist, the candidate proposes the establishment of a SCLC tumor bank by xenogeneic transplantation of tumor samples to immunodeficient mice during this period of mentored training. This unique resource will support ongoing and future preclinical evaluation of new anticancer agents and facilitate the understanding of the unique biology of SCLC. Simultaneous with this intense practical experience in patient-oriented research, the candidate will participate in a formal well-structured didactic curriculum leading to the award of a Masters of Science in Clinical Research from his home institution, Emory University. This course of study is a rigorous multi-year curriculum designed to provide participants with a deep knowledge and comprehensive understanding of the ethics, design, conduct and regulation of patient-oriented research. This overall training and practical experience will occur under the lead mentorship of Dr. Fadlo Khuri, an accomplished translational researcher with track record of successfully mentoring all cadres of clinicians and basic scientists. He will be assisted by co-mentors with complementary expertise including Suresh Ramalingam, MD, an internationally renowned clinical investigator with superb expertise in lung cancer; Shi-Yong Sun, PhD, a highly experienced basic scientist and a world leader in mTOR biology; and Mourad Tighiouart, PhD, a biostatistician with strong interest in design of clinical trials to evaluate promising anticancer agents. This training program will occur at Emory University and the Winship Cancer Institute of Emory University which provide an ideal environment for learning, training and practical exposure in patient-oriented research and a unique opportunity for collaboration between basic scientists and clinical investigators. The Winship Cancer Institute is an NCI-designated cancer center which ensures the proper conduct of investigator-initiated single center studies as well as participation in large cooperative group clinical trials as proposed in this application. It is expected that at the end of this mentoring period, the candidate will be adequately prepared to pursue an independent research career focused on SCLC and will be highly competitive for research funding and academic leadership roles.

描述（由申请人提供）：该候选人是埃默里大学血液学和医学肿瘤学的助理教授。他的长期职业目标是成为一名独立翻译研究人员，在肺癌患者的临床护理方面具有公认的卓越专业知识，进行临床试验，导致新的发展 小细胞肺癌（SCLC）的治疗方案以及对新型化合物的临床前评估，可能会发展为有效的SCLC疗法。候选人有兴趣通过研究新的治疗方案和制定有效的策略来提高目前可用疗法的功效，从而提高SCLC患者的护理和临床结果。候选人提出了一项职业发展计划，其中包括一项多方面的培训和指导计划，旨在提供激烈的，以患者为导向的研究经验。这些目标将通过他在招募SCLC患者的两项临床试验的设计和行为中的领导作用来实现。第一个试验是由HE候选人设计的单一机构研究，该研究将评估三氧化砷在复发性疾病中的临床功效。如果成功，这项临床试验将将一种新颖的疗法引入到难治性患者人群的治疗选择中。第二个临床试验是候选人的直接翻译 临床前实验室工作旨在评估添加口服的PARP抑制剂ABT-888是否会增强标准化学疗法剂的疗效，而不会增加新诊断的SCLC患者的毒性。这项研究计划作为一项多机构临床试验，该试验旨在通过已建立的ECOG合作组机制进行。此外，为了为作为翻译科学家的长期职业做准备，候选人提议在这段受过训练的培训期间，通过对肿瘤样本的异种移植对免疫缺陷小鼠建立SCLC肿瘤库。这种独特的资源将支持对新抗癌剂的持续和未来的临床前评估，并促进对SCLC独特生物学的理解。候选人同时，与以患者为导向的研究相同的实践经验，将参加正式的结构良好 教学课程导致埃默里大学的家庭机构授予临床研究的科学硕士学位。这项研究课程是一项严格的多年课程，旨在为参与者提供对伦理，设计，行为和调节患者研究的深入了解和全面的了解。这项整体培训和实践经验将在Fadlo Khuri博士的主要指导下发生，Fadlo Khuri博士是一位有成就的翻译研究人员，其记录是成功指导所有临床医生和基础科学家的干部。他将得到具有互补专业知识的联席会员的协助，其中包括国际知名的临床研究者Suresh Ramalingam，MD，具有肺癌的最高专业知识； Shi-Yong Sun，PhD，一位经验丰富的基础科学家和MTOR生物学的世界领导者；以及Mourad Tighiouart博士，一位生物统计学家，对设计临床试验的设计浓厚兴趣，以评估有希望的抗癌药。该培训计划将在埃默里大学（Emory University）和埃默里大学（Emory University）的Winship Cancer Institute举行，该研究所为以患者的研究为学习，培训和实践曝光提供了理想的环境，并为基础科学家与临床研究人员之间的合作机会提供了独特的机会。 Winship Cancer Institute是一个NCI指定的癌症中心，可确保调查员引入的单一中心研究以及参与大型合作小组 本应用中提出的临床试验。可以预期，在这一指导期结束时，候选人将做好充分的准备，以从事专注于SCLC的独立研究职业，并且在研究资金和学术领导角色方面将具有很高的竞争力。