NCI Experimental Therapeutics-Clinical Trials Network with Phase 1 Emphasis

NCI 实验治疗-临床试验网络，重点为 1 期

基本信息

批准号：
9086290
负责人：
ALEX A. ADJEI
金额：
$ 71.82万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-07 至 2020-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9086290
关键词：
Affect Aftercare Antineoplastic Agents Apoptosis Apoptosis Regulation Gene Biochemical Biochemical Pathway Biological Biological Markers Biological Models Biopsy CLIA certified Cancer Center Cell Cycle Checkpoint Cell Survival Clinical Clinical Trials Clinical Trials Network Communities DNA Repair Pathway Data Dose Drug Combinations Drug Kinetics Drug Targeting Drug toxicity Eastern Cooperative Oncology Group Eligibility Determination Environment Enzymes Evaluation Functional disorder Funding Genetic Polymorphism Genomics Grant Hand Image Imaging Techniques Immune system Immunotherapeutic agent In Vitro Investigational Therapies Laboratories Malignant Neoplasms Maryland Maximum Tolerated Dose Mayo Clinic Cancer Center Measures Molecular Molecular Target Monitor National Cancer Institute New Agents North Central Cancer Treatment Group Organ Pathway interactions Patients Peer Review Pharmaceutical Preparations Pharmacogenetics Phase Phase I Clinical Trials Phase II/III Trial Population Population Heterogeneity Pre-Clinical Model Regimen Regulation Resources Schedule Scheme Science Scientist Signal Transduction Pathway Testing Therapeutic Clinical Trial Therapeutic Effect Therapeutic Intervention Titrations Toxic effect Translating Translations Universities angiogenesis antitumor effect base chemotherapy clinical effect design genomic biomarker instrument named group novel novel anticancer drug outcome prediction patient safety pharmacodynamic model phase 1 study phase II trial potential biomarker pre-clinical programs response targeted agent therapeutic evaluation trial design tumor

项目摘要

DESCRIPTION (provided by applicant): We will conduct Phase I clinical trials of new anticancer agents or combinations of anticancer agents to characterize drug toxicity, determine the maximum tolerated dose, evaluate the pharmacokinetics, perform pharmacogenetic analysis, and relating clinical endpoints to pharmacokinetics, pharmacogenetics, and/or biologic endpoints. A major focus of this proposal is the study agents that interact with novel targets such as signal transduction pathways, cell cycle checkpoint components, DNA repair pathways and apoptosis regulators, either alone or in combination with standard chemotherapy. The endpoints for the evaluation of such treatments will be clinical effect (toxicity and antineoplasti response) as well as alterations in biochemical pathways affected in preclinical model systems. The specific aims of these studies are: to determine as efficiently as compatible with patient safety the appropriate dose of new anticancer agents selected by the National Cancer Institute using novel trial designs including accelerated titration, Bayesian design, and other advanced design schemes; to identify clinical, pharmacokinetic, or other laboratory parameters that may predict toxicity; to determine whether functional polymorphisms of drug metabolizing or other enzymes associated with drug response alter pharmacokinetics, toxicity and/or activity of agents being studied; to obtain mechanistic proof-of-principle data for new agents directed at novel molecular cancer targets when appropriate; to evaluate translational endpoints in clinical trials o investigational agents such as, levels of expression and/or activity of molecular targets and/or downstream effectors pertinent to a given agent or pathway modulated by the agent under study; to identify potential biomarkers (with particular emphasis where possible on genomics and imaging) that may serve as predictors of outcome in later phase trials; to translate novel discoveries from R0l, SPORE, or other peer reviewed mechanisms into clinical trials that leverage the scientific community expertise with a team science approach. Studies will be designed to incorporate the appropriate pharmacokinetic and pharmacogenetic analysis, drug analysis, and biological analysis of drug effects on the intended target or pathway. RELEVANCE: The Mayo Clinic Cancer Center and University of Maryland Greenebaum Cancer Center provides an exceptional environment to perform early phase trials in a diverse population. The team environment and expertise of the 2 centers that will be brought to focus on phase 1 trials will facilitate translation of novel preclinical discoveries into treatments that ca be assessed for efficacy in Phase II and Phase III trials.

描述（由申请人提供）：我们将对新的抗癌剂或抗癌剂组合进行I期临床试验，以表征药物毒性，确定最大耐受剂量，评估药代动力学，进行药物遗传学分析，并将临床端点与药代动力学，药物遗传学和生物学终结点相关。该提案的主要重点是与新靶标相互作用的研究代理，例如单独或与标准化学疗法结合使用，例如信号转导途径，细胞周期检查点组件，DNA修复途径和凋亡调节剂。评估此类治疗的终点将是临床效应（毒性和抗肿瘤反应），以及在临床前模型系统中影响的生化途径的改变。这些研究的具体目的是：使用新型试验设计，包括加速滴定，贝叶斯设计和其他先进的设计方案，以确定与患者安全兼容的适当剂量。确定可能预测毒性的临床，药代动力学或其他实验室参数；确定药物代谢的功能多态性或与药物反应相关的其他酶是否会改变药代动力学，毒性和/或研究剂的活性；为了获得适用于新的分子癌靶标的新药物的机械原理数据；在临床试验中评估翻译终点o研究剂，例如分子靶标的表达和/或活性水平和/或与所研究药物调节的给定药物或途径有关的分子靶标和/或下游效应子；确定潜在的生物标志物（在可能的情况下特别强调基因组学和成像），可以作为后期试验的结果的预测指标；将R0L，Spore或其他同行审查机制的新发现转化为临床试验，以通过团队科学方法来利用科学社区的专业知识。研究将旨在纳入适当的药代动力学和药物遗传学分析，药物分析以及对预期靶点或途径的药物影响的生物学分析。相关性：梅奥诊所癌症中心和马里兰州格林巴姆大学癌症中心为在多样化人群中进行早期试验提供了一个非凡的环境。将重点关注1阶段试验的两个中心的团队环境和专业知识将有助于将新颖的临床前发现转化为CA在II阶段和第三阶段试验中的疗效评估的治疗方法。