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: 8226264
• 负责人: Taofeek K Owonikoko
• 金额: $ 16.36万
• 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/8226264
• 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; 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助理教授。他的长期职业目标是成为一名独立的翻译研究人员，在肺癌患者的临床护理方面具有公认的上级专业知识，进行临床试验，开发新的 小细胞肺癌（SCLC）的治疗选择，并在临床前评估的新化合物可能发展成为有效的治疗SCLC。候选人有兴趣通过研究新的治疗方案和开发有效的策略来提高SCLC患者的护理和临床结果，以改善目前可用的治疗方法的疗效。候选人提出了一个职业发展计划，其中包括一个多方面的培训和指导计划，旨在提供一个激烈的，以病人为导向的研究经验。这些目标将通过他在设计和进行两项招募SCLC患者的临床试验中的领导作用来实现。第一项试验是由候选人设计的单机构研究，将评估三氧化二砷在复发性疾病中的临床疗效。如果成功，这项临床试验将为难治性患者人群的治疗选择引入一种新的疗法。第二个临床试验是直接翻译候选人的 临床前实验室工作，旨在评估ABT-888（一种口服PARP抑制剂）的加入是否会增强标准化疗药物的疗效，而不会增加新诊断的SCLC患者的毒性。本研究计划作为一项多机构临床试验，通过ECOG已建立的协作组机制进行。此外，在准备作为一个长期的职业生涯作为一个翻译科学家，候选人提出建立一个SCLC肿瘤库的异种移植肿瘤样本的免疫缺陷小鼠在这段时间的指导培训。这种独特的资源将支持正在进行的和未来的新抗癌药物的临床前评价，并促进对SCLC独特生物学的理解。同时，在以患者为导向的研究中，候选人将参加一个正式的结构良好的 他的教学课程使他获得了家乡埃默里大学的临床研究科学硕士学位。本课程是一个严格的多年课程，旨在为参与者提供深入的知识和对以患者为导向的研究的道德，设计，行为和监管的全面理解。这种整体培训和实践经验将在Fadlo Khuri博士的领导指导下进行，他是一位成功的翻译研究员，成功地指导了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共同导师的协助，包括Suresh Ramalingam，医学博士，国际知名的临床研究者，在肺癌方面具有卓越的专业知识; Shi-Yong Sun，博士，经验丰富的基础科学家和mTOR生物学的世界领导者;以及Mourad Mesiouart，博士，生物统计学家，对临床试验设计有浓厚兴趣，以评估有前途的抗癌药物。该培训计划将在埃默里大学和埃默里大学温希普癌症研究所进行，为以患者为导向的研究提供学习，培训和实际接触的理想环境，以及基础科学家和临床研究人员之间合作的独特机会。Winship癌症研究所是一家NCI指定的癌症中心，它确保了由癌症研究所发起的单中心研究的正确进行，以及参与大型合作小组。 本申请中提出的临床试验。预计在此指导期结束时，候选人将充分准备追求专注于SCLC的独立研究生涯，并将在研究资金和学术领导角色方面具有很强的竞争力。