Use of Patient-Reported Outcomes in Understanding Symptomatic Adverse Events in Early-Phase Trials of Combination Treatments that Include Immune Checkpoint Inhibitors and Targeted Therapy

使用患者报告的结果来了解包括免疫检查点抑制剂和靶向治疗在内的联合治疗早期试验中的症状不良事件

• 批准号: 10533725
• 负责人: Goldy C George
• 金额: $ 14.68万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-05 至 2025-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10533725
• 关键词: Acceleration; Acute; Address; Advanced Malignant Neoplasm; Adverse event; Affect; Aftercare; Antineoplastic Agents; Arthralgia; Back; Chills; Clinical; Clinical Treatment; Colitis; Combination immunotherapy; Combined Modality Therapy; Community Clinical Oncology Program; Coupled; Data; Decision Making; Detection; Deterioration; Development; Diarrhea; Disease; Dizziness; Dose; Early Diagnosis; Early Intervention; Early identification; Ensure; Event; Fatigue; Fever; Headache; Heart; Immune; Immune checkpoint inhibitor; Immunotherapy; Institution; Intervention; Knowledge; Late Effects; Malignant Neoplasms; Measures; Mission; Monitor; Moon; Myalgia; National Cancer Institute; Nausea; New Agents; Nivolumab; Outcome; Palpitations; Patient Outcomes Assessments; Patients; Pharmaceutical Preparations; Phase I Clinical Trials; Public Health; Publishing; Pulmonary Inflammation; Quality of life; Recommendation; Reporting; Research; Research Personnel; Risk; Safety; Shortness of Breath; Supportive care; Swelling; Symptoms; Therapeutic; Therapy trial; Time; Toxic effect; United States Food and Drug Administration; University of Texas M D Anderson Cancer Center; Vomiting; Work; cancer immunotherapy; cancer therapy; checkpoint therapy; cohort; compliance behavior; disabling symptom; drug development; early phase clinical trial; early phase trial; experience; gastrointestinal symptom; immune-related adverse events; improved; ipilimumab; optimism; pembrolizumab; precision medicine; prevent; side effect; standard of care; survival outcome; symptom cluster; symptom management; targeted treatment; treatment response

PROJECT SUMMARY Breakthroughs in cancer immunotherapy have excited patients and clinicians and have brought optimism back into the oncology community. However, these therapies are often effective for only a percentage of patients, and some patients may even be at risk for serious and sometimes fatal toxicities related to the therapy. Unlike the toxicities induced by standard therapies, immune-related adverse events (irAEs) are just becoming appreci- ated, and side effect profiles for new immunotherapies are often poorly understood. Further contributing to this issue is the increasing use of therapies that combine immune checkpoint inhibitors approved by the US Food and Drug Administration (eg, nivolumab, pembrolizumab) with other checkpoint inhibitors or targeted thera- pies. The unique toxicities of such combination therapies remain largely unknown and need to be tracked, so that their immune-related safety profiles can be characterized and adequately managed. Researchers at The Uni- versity of Texas MD Anderson Cancer Center propose to use patient-reported outcomes (PROs) to capture symptomatic irAEs of combination therapies that include checkpoint inhibitors, taking advantage of the large number of early-phase trials of these therapies already in place in the institution's Department of Investigational Therapeutics, coupled with the expertise in longitudinal symptom assessment in the Department of Symptom Research. The Specific Aims of the study are: (1) to identify, track, and evaluate emerging symptomatic toxic- ities and symptom burden during early-phase clinical trials of treatments that include immune checkpoint in- hibitors in combination with other checkpoint inhibitors or targeted therapies; and (2) to investigate relation- ships between longitudinal patient-reported symptoms and clinical outcomes (eg, development of moderate-to- severe irAEs, time to treatment discontinuation, time to deterioration) in early-phase trials of combination treat- ments that include checkpoint inhibitors, and to investigate whether moderate to severe irAEs are predicted by increases in relevant symptoms prior to the event. The study's clinical impact will be early detection of irAEs associated with combination therapies that include checkpoint inhibitors, to facilitate proactive intervention. Worsening symptoms may presage the emer- gence of their clinical manifestations and allow for appropriate supportive care or for other treatment decisions to be made. PROs are an essential component of cancer drug development, without which clinicians and regu- lators have an incomplete picture of how patients are affected by a new agent. PROs will provide invaluable pa- tient perspectives on the symptomatic effects of combination treatments that include immune checkpoint in- hibitors to multiple stakeholders in early drug development (eg, patients, sponsors, regulators, and payers). This project addresses Recommendation F in the Cancer Moon Shot Blue Ribbon Panel 2016 report, which calls for accelerated research to monitor and manage patient-reported symptoms, not only for improving quality of life, but also for ensuring patient adherence to treatments that will improve therapeutic response. 1

项目摘要 癌症免疫疗法的突破使患者和临床医生感到兴奋，并带来了乐观 回到肿瘤学社区。但是，这些疗法通常仅对一定比例的患者有效， 一些患者甚至可能面临与治疗有关的严重毒性，有时甚至是致命毒性的风险。与众不同 标准疗法引起的毒性，与免疫相关的不良事件（IRAE）只是在欣赏 新免疫疗法的ATED和副作用概况通常对了解不足。进一步贡献 问题是越来越多地使用美国食品批准的免疫检查点抑制剂 和药物给药（例如Nivolumab，pembrolizumab）具有其他检查点抑制剂或靶向thera- 派。这种组合疗法的独特毒性在很大程度上尚不清楚并且需要进行跟踪，因此 可以将其与免疫相关的安全概况进行表征和充分管理。大学的研究人员 德克萨斯州Anderson Cancer Center的Versity建议使用患者报告的结果（PRO）捕获 有症状的组合疗法的IRAE，包括检查点抑制剂，利用大型 这些疗法的早期试验数量已经在该机构的研究部 治疗剂，再加上症状纵向症状评估的专业知识 研究。该研究的具体目的是：（1）识别，跟踪和评估新兴的症状有毒毒性 - 在包括免疫检查点的治疗早期临床试验期间的ITIE和症状负担 与其他检查点抑制剂或靶向疗法结合使用； （2）研究关系 - 纵向患者报告的症状和临床结局之间的船只（例如，中等到中等 严重的伊拉斯，治疗停止的时间，劣化时间） 包括检查点抑制剂的媒介，并调查是否预测中度至重度伊拉斯 事件发生前的相关症状增加。 该研究的临床影响将是对与联合疗法相关的伊拉斯的早期发现 包括检查点抑制剂，以促进主动干预。恶化的症状可能会预示 其临床表现的意义，并允许适当的支持护理或其他治疗决策 要制作。优点是癌症药物开发的重要组成部分，没有这些组成部分 LATORS对患者如何受到新代理的影响不完整。专业人士将提供宝贵的PA- 关于包括免疫检查点的组合治疗的症状作用的特点观点 早期药物开发中多个利益相关者（例如，患者，赞助商，监管机构和付款人）的招募者。 该项目涉及癌症月球射击蓝带面板2016年报告中的建议f， 它要求加速研究以监测和管理患者报告的症状，不仅用于改善 生活质量，也可以确保患者遵守可以改善治疗反应的治疗方法。 1