Determining Mechanisms and Measures for the Design of Chemotherapy-Induced Peripheral Neuropathy Clinical Trials in Adolescents and Young Adults with Cancer

确定青少年和年轻癌症患者化疗引起的周围神经病变临床试验设计的机制和措施

• 批准号: 9975385
• 负责人: Robert James Knoerl
• 金额: $ 11.32万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-04 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9975385
• 关键词: Address; Adolescent and Young Adult; Adult; Algorithms; Biological; Biological Markers; Chemotherapy-induced peripheral neuropathy; Chronic; Clinical; Clinical Sciences; Clinical Trials; Clinical Trials Design; Coenzymes; Common Terminology Criteria for Adverse Events; Complication; Dana-Farber Cancer Institute; Development; Development Plans; Dinucleoside Phosphates; Dose; Dose-Limiting; Environment; Extramural Activities; Functional disorder; Funding; Future; Genes; Genomics; Genotype; Goals; Hand; Individual; Intervention; Knowledge; Laboratories; Longitudinal Studies; Malignant Neoplasms; Measurement; Measures; Metabolic; Michigan; Microtubules; Mission; National Institute of Nursing Research; Neurons; Neuropathy; Nicotinamide adenine dinucleotide; Numbness; Outcome; Outcome Measure; Outcomes Research; Paclitaxel; Pain; Patient Outcomes Assessments; Physical Function; Physiological; Postdoctoral Fellow; Prevention; Preventive Intervention; Property; Psychometrics; Public Health; Quality of life; Questionnaires; Randomized Controlled Trials; Reporting; Research; Research Personnel; Research Training; Resources; Risk; Sample Size; Self Management; Serum; Severities; Stratification; Symptoms; Testing; Time; Toxic effect; Training; Translational Research; Universities; Vincristine; Work; Yoga; axonal degeneration; axonopathy; base; cancer therapy; career; career development; chemotherapy; clinical development; design; efficacy study; efficacy testing; experience; foot; functional disability; high risk; improved; innovation; leukemia/lymphoma; malignant breast neoplasm; metabolomics; mortality; mortality risk; negative affect; neurotoxic; nicotinamide-beta-riboside; preclinical study; preservation; prevent; prevention clinical trial; skills; symptom management; symptom science; treatment response; treatment strategy; trial design; young adult

Project Summary Long-TermCareer Goal: Dr. Knoerl’s long-term career goal is to decrease suffering and maximize chemotherapy dosing in adolescents and young adults (AYAs) by identifying translational treatment strategies for chemotherapy-induced peripheral neuropathy (CIPN). Clinical Problem: CIPN (e.g., numbness/tingling in hands/feet) is a common complication of vincristine/paclitaxel chemotherapy that is associated with reductions in chemotherapy dosing, thereby increasing the risk of mortality. Yet, there are no recommended treatments for CIPN prevention and little is known about CIPN in AYAs to guide the development of clinical trials. Candidate Background: Dr. Knoerl trained at the University of Michigan and gained expertise leading CIPN management trials by conducting a randomized controlled trial to test the efficacy of an online self- management intervention for chronic painful CIPN. Dr. Knoerl is currently a postdoctoral fellow at Dana-Farber Cancer Institute (DFCI) and has earned internal funding to study the efficacy of a clinician decision support algorithm to improve CIPN assessment; and extramural funding to explore the impact of yoga for CIPN. Career Development Plan: The conduct of this K23 proposal will further advance the candidate to his goal of becoming an independent, translational symptom science investigator by providing him with specific training in 1) the measurement and analysis of metabolic and genomic intermediaries, 2) mechanisms of CIPN development, and 3) the design, measurement, and analysis of patient-reported outcomes in a clinical trial. DFCI is an optimal environment for training as the candidate will have access to experts, coursework, and resources aligned with the research and training aims. Specific Aims: The overall objective of this longitudinal study is to determine factors crucial to the design of CIPN prevention clinical trials for AYAs with cancer. The primary aim is to determine the association between serum nicotinamide riboside dinucleotide (NAD+) levels and CIPN severity and associated functional interference. Secondary aims are to 1) evaluate the association between the high risk CEP72 (TT at rs924607) genotype and CIPN severity and associated functional impairment 2) examine the psychometric properties of the Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy (QLQ-CIPN20). Expected Outcomes: Establishing NAD+ as a physiological influencing factor of CIPN development will direct future work towards the testing of interventions to boost NAD+ for CIPN prevention. The identification of CEP72 as a biomarker of CIPN will increase statistical power and allow for the stratification of AYAs examine treatment response in future trials. Determining the psychometric properties of the QLQ-CIPN20 will aid in the identification of efficacious CIPN interventions in AYAs.

项目摘要 长期护理目标：Knoerl博士的长期职业目标是减少苦难和最大化 通过识别转化治疗策略，青少年和年轻人（AYA）的化学疗法给药 用于化学疗法诱导的周围神经病（CIPN）。 临床问题：CIPN（例如，手/脚的麻木/刺痛）是常见的并发症 长春新碱/紫杉醇化学疗法与化学疗法降低有关的化学疗法，从而 增加死亡率的风险。但是，没有建议预防CIPN的治疗方法，几乎​​没有 有关AYA中CIPN的知名度，以指导临床试验的发展。 候选人背景：Knoerl博士在密歇根大学培训，并获得了领导CIPN的专业知识 管理试验通过进行随机对照试验来测试在线自我的效率 慢性疼痛CIPN的管理干预。 Knoerl博士目前是Dana-Farber的博士后研究员 癌症研究所（DFCI）并赢得了内部资金来研究临床决策支持的效率 改善CIPN评估的算法；和壁外资金，以探索瑜伽对CIPN的影响。 职业发展计划：该K23提案的行为将进一步推动候选人的目标 通过为他提供特定的培训，成为独立的，翻译的症状科学研究者 1）代谢和基因组中介机构的测量和分析，2）CIPN机制 开发以及3）在临床试验中对患者报告结果的设计，测量和分析。 DFCI 是培训的最佳环境，因为候选人将可以访问专家，课程和资源 与研究和培训目标保持一致。 具体目的：这项纵向研究的总体目标是确定对设计至关重要的因素 针对癌症的AYA的CIPN预防临床试验。主要目的是确定 血清烟酰胺核苷二核苷酸（NAD+）水平和CIPN严重程度和相关功能 干涉。次要目的是1）评估高风险CEP72之间的关联（TT为RS924607） 基因型和CIPN严重程度以及相关的功能障碍2）检查的心理测量特性 生活质量问卷 - 化学治疗诱导的周围神经病（QLQ-CIPN20）。 预期结果：将NAD+建立为CIPN开发的物理影响因素将指导 为了测试干预措施以提高NAD+预防CIPN的未来工作。识别 CEP72作为CIPN的生物标志物将增加统计能力，并允许AYAS的分层检查 将来的试验中的治疗反应。确定QLQ-CIPN20的心理测量特性将有助于 鉴定AYA中有效的CIPN干预措施。