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肿瘤内科助理教授。他的长期职业目标是成为一名独立的转化研究员，在肺癌患者的临床护理、开展临床试验以开发新的药物方面拥有公认的卓越专业知识。 小细胞肺癌 (SCLC) 的治疗选择以及可能发展为 SCLC 有效疗法的新型化合物的临床前评估。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当前可用疗法的疗效，从而推进 SCLC 患者的护理和临床结果。候选人提出了一份职业发展计划，其中包括旨在提供密集、以患者为导向的研究经验的多方面培训和指导计划。这些目标将通过他在设计和开展两项招募 SCLC 患者的临床试验中发挥的主导作用来实现。第一项试验是由候选人设计的一项单一机构研究，旨在评估三氧化二砷治疗复发性疾病的临床疗效。如果成功，这项临床试验将为难治性患者群体的治疗选择中引入一种新疗法。第二次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 ABT-888（一种口服 PARP 抑制剂）是否会增强标准化疗药物的疗效，而不增加新诊断 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既定的合作组机制进行。此外，为了准备作为转化科学家的长期职业生涯，候选人建议在指导培训期间通过将肿瘤样本异种移植到免疫缺陷小鼠体内来建立 SCLC 肿瘤库。这一独特的资源将支持正在进行的和未来的新型抗癌药物的临床前评估，并促进对 SCLC 独特生物学的理解。在以患者为导向的研究中获得丰富的实践经验的同时，候选人将参加一个正式的、结构良好的项目 教学课程使他获得了家乡埃默里大学临床研究理学硕士学位。本课程是一门严格的多年课程，旨在让参与者对以患者为中心的研究的伦理、设计、实施和监管有深入的了解和全面的理解。这种整体培训和实践经验将在 Fadlo Khuri 博士的指导下进行，Fadlo Khuri 博士是一位出色的转化研究员，拥有成功指导所有临床医生和基础科学家骨干的记录。他将得到具有互补专业知识的共同导师的协助，其中包括医学博士 Suresh Ramalingam，他是一位国际知名的临床研究人员，在肺癌方面拥有精湛的专业知识；孙世勇博士，一位经验丰富的基础科学家，mTOR 生物学领域的世界领先者； Mourad Tighiouart 博士是一位生物统计学家，他对设计临床试验来评估有前景的抗癌药物有着浓厚的兴趣。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，该研究所为学习、培训和以患者为导向的研究实践接触提供了理想的环境，并为基础科学家和临床研究人员之间的合作提供了独特的机会。 Winship 癌症研究所是 NCI 指定的癌症中心，确保研究者发起的单中心研究的正确进行以及大型合作小组的参与 本申请中提出的临床试验。预计在本指导期结束时，候选人将为从事 SCLC 的独立研究职业做好充分准备，并将在研究经费和学术领导角色方面具有高度竞争力。