Angiogenic biomarker discovery to direct bevacizumab therapy in cervical cancer - Blood-based Angiome Profiling: An ancillary analysis of GOG-0240

血管生成生物标志物的发现可指导宫颈癌贝伐单抗治疗 - 基于血液的血管瘤分析：GOG-0240 的辅助分析

• 批准号: 10112674
• 负责人: ANDREW B. NIXON
• 金额: $ 26.8万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10112674
• 关键词: Address; Angiogenesis Inhibitors; Biological Markers; Biological Response Modifier Therapy; Blood; Cancer Burden; Cancer Patient; Cessation of life; Clinical; Combination immunotherapy; Development; Disease; Enrollment; Event; Foundations; Future; Goals; Growth Factor; Gynecologic Oncology Group; Healthcare; Hemangioma; Hypertension; Immune response; Immunotherapy; Inflammation; Inflammatory Response; Interleukin-6; Laboratories; Maintenance; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Malignant neoplasm of ovary; Malignant neoplasm of pancreas; Measures; Outcome; Paclitaxel; Participant; Patients; Phase; Plasma; Predictive Factor; Progression-Free Survivals; Proteins; Randomized; Recurrence; Research; Resources; Role; Sampling; Signal Pathway; Solid Neoplasm; Specimen; Statistical Data Interpretation; System; Technology; Testing; Toxic effect; Tumor Angiogenesis; United States Food and Drug Administration; Woman; angiogenesis; base; bevacizumab; biomarker discovery; cancer therapy; candidate marker; chemotherapy; cost; cost effective; cytokine; design; improved; improved outcome; interest; kidney cell; novel; open label; phase III trial; placebo controlled trial; predict clinical outcome; predictive marker; prognostic; prognostic of survival; research and development; response; survival outcome; taxane; therapy development; thrombotic; treatment comparison; treatment group; tumor microenvironment

Project Summary The anti-angiogenic agent bevacizumab (BEV) is one of the most effective forms of biologic therapy developed thus far for cervical cancer (CC). However, response is variable, BEV is expensive, and significant toxicity may occur. Given the projected increase in the global burden of cancer and limited health care resources, it is imperative that research be conducted to define patients that will truly benefit from expensive therapies. The development of an angiogenic biomarker to direct the use of BEV could maximize benefit, as well as minimize toxicity and cost. My collaborator, Dr. Andrew Nixon, and his team at Duke have developed a protein-based plasma multiplex array (angioma) that consists of 26 growth factors and cytokines involved in angiogenesis and inflammation. We propose to evaluate our most promising biomarker, interleukin-6 (IL-6), which has demonstrated predictive efficacy for BEV in other solid tumors, in women with advanced metastatic CC enrolled on the Gynecologic Oncology Group (GOG) 240. Our primary aim is to determine if IL-6 levels can be utilized to direct BEV therapy for women with CC. The pivotal phase III GOG-0240, a 2x2 bifactorial placebo- controlled trial of taxane-based chemotherapy with and without BEV is the ideal platform to assess biomarkers. Our specific aims will determine if (a) baseline IL-6 is predictive of BEV benefit based on survival outcomes, (b) other angiome biomarkers are predictive and/or prognostic of survival outcomes in women with advanced CC and c) angiome biomarker change is associated with outcome and response. Plasma samples at baseline and pre-cycle 2 from GOG-0240 will be analyzed in Dr. Nixon’s laboratory using several multiplex systems including technology from Quanterix Corporation, MesoScaleDiscovery, and Protein Simple (R&D Systems). Statistical analyses will be performed to identify and validate biomarkers of interest. Kaplan-Meier plots and log-rank tests will compare treatment groups. Our ultimate goal is to improve the outcome for women with CC by rationally directing BEV therapy; minimizing toxicity and cost; and identifying novel targets to develop future anti-angiogenic therapies. We anticipate that our research will help to harmonize analyses across other malignancies, which will be critical for understanding if IL-6 and other candidate biomarkers predictive of BEV efficacy are, or are not, disease specific.

项目摘要 抗血管生成剂贝伐单抗（BEV）是开发的生物疗法的有效形​​式 到目前为止，宫颈癌（CC）。 鉴于全球癌症负担和有限的医疗保健资源的预计增加 必须进行研究，以定义将真正受益于某些疗法的患者 开发直接使用BEV的血管生成生物标志物可以最大程度地提高利益，并最小化 毒性和成本。 血浆多重阵列（血管瘤）由26种生长因子和细胞因子组成 和炎症。 在其他实体瘤中证明了BEV的预测功效，在患有晚期CC的女性中 注册妇科肿瘤学组（GOG）240。我们的主要目的是确定IL-6水平是否可以 使用CC直接进行BEV治疗。 基于紫杉烷的化学疗法和与BEV的对照试验是评估生物标志物的理想平台。 我们的具体目的将确定（a）基线IL-6是否基于生存结果来预测收益，（b） 其他血管群生物标志物是晚期CC女性生存结果的预测性和/或预后 c）血管组生物标志物变化与基线和血浆样本有关。 GOG-0240的前循环2使用多个多重系统将在尼克松博士的实验室中进行 来自Quanterix Corporation，Messoscaliscovery和Protein Simple（R＆D Systems）的技术。 将进行统计分析以识别和验证感兴趣的生物标志物。 对数秩检验将比较我们的最终目标。 通过理性地指导BEV治疗； 抗Ngiogenic疗法。 Malignnancies，这对于理解IL-6和其他候选生物标志物是否预测BEV至关重要 疗效是或非特定于疾病的。