Biomarker Studies for Novel Anti-Cancer Agents

新型抗癌药物的生物标志物研究

• 批准号: 7281618
• 负责人: OLIVER MICHAEL COLVIN
• 金额: $ 6.22万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-28 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7281618
• 关键词: Academic Medical Centers; Address; Adverse event; Ambulatory Care Facilities; American Joint Committee on Cancer; Antineoplastic Agents; Beds; Biological Markers; Brain Neoplasms; Cancer Biology; Cancer Center; Cancer Patient; Caring; Charge; Class; Clinic; Clinical; Clinical Data; Clinical Pharmacology; Clinical Research; Clinical Treatment; Clinical Trials; Collection; Common Terminology Criteria for Adverse Events; Community Clinical Oncology Program; Complex; Computerized Medical Record; Computers; Conduct Clinical Trials; Consent; Contracts; Cost Savings; Country; Data; Data Collection; Databases; Depth; Development; Diagnostic Neoplasm Staging; Discipline of Nursing; Dose; Dose-Limiting; Drug Kinetics; Duke Comprehensive Cancer Center; Education; Electronics; End Point; Epidermal Growth Factor Receptor; Evaluation; Goals; Growth Factor Inhibition; Hospitals; Image; Information Services; Infusion procedures; Inpatients; Internet; Kinetics; Laboratories; Licensing; Measurement; Medical; Medical History; Medical center; Metabolism; Modeling; Molecular Target; New Agents; North Carolina; Office for Protection from Research Risks; Other Therapy; Outpatients; PDGFRB gene; Patient Care; Patient Monitoring; Patients; Pharmacodynamics; Pharmacology; Pharmacy facility; Phase; Phase I Clinical Trials; Physicians; Physiological; Pliability; Population; Process; Property; Protocols documentation; Provider; Quality of life; Radiation therapy; Radioisotopes; Radiology Specialty; Reporting; Research; Research Ethics Committees; Research Infrastructure; Resources; Role; Safety; Schedule; Signal Transduction; Southeastern United States; Standards of Weights and Measures; Stromal Neoplasm; System; Time; Toxic effect; Tumor Angiogenesis; Tumor stage; Tyrosine Kinase Inhibitor; United States; United States National Institutes of Health; Universities; University Hospitals; VEGFR inhibition; Visit; Writing; absorption; base; cancer care; chemotherapy; computerized; farnesyltranstransferase; follow-up; improved; innovation; interest; novel; novel vaccines; oncology; programs; protein farnesyltransferase; receptor; research clinical testing; response; tumor

DESCRIPTION (provided by applicant): The overall goal of this UO1 phase I application is to efficiently and safely conduct dose finding, pharmacological, and bio-marker evaluation clinical trials of novel anti-cancer agents from the NCI. Information from phase I studies will guide selection of optimal dose and schedule for further study. Most new anti-cancer agents are mechanism-based, have limited toxicities, limited single agent activity, and may be most effective in combination with other therapies, or in populations expressing a specific molecular target or targets. For successful development of such agents, it is essential to provide evidence that these agents hit the intended molecular targets in patients before moving these agents into full scale clinical development. It is also critical to better understand the physiological consequences of this effect in relation to the new agent's activity and toxicity early in clinical development. We propose the following specific aims: 1.To define and describe agents' dose limiting and non-dose limiting toxicities, and provide evidence of clinical activity. 2. To define the pharmacokinetic properties of novel agents, including absorption, distribution, metabolism, and elimination. We will evaluate the pharmacodynamic effect of these parameters on toxicity, efficacy, and target inhibition or stimulation. 3. To evaluate novel biomarker and/or imaging studies that will provide proof of principle for an agent's activity at the target level, and to correlate these with other clinical and pharmaco- kinetic /pharmacodynamic endpoints. 4. To define a phase II dose based upon all available toxicity, efficacy, PK, PD, imaging, and biomarker data. Since the novel agents that will become available in the NCI pipeline are not completely known at this time, we will focus our approaches on classes of agents for which we have both scientific expertise and a track record of productive translational clinical investigation, including, 1) agents targeting tumor angiogenesis; 2) agents targeting tumor or tumor-stromal growth factor inhibition; and 3) novel vaccine and other immunomodulatory agents. We are also expert in studying agents targeted to brain tumor patients for phase I agents. We anticipate 2-3 studies per year. We will emphasize single agent studies but can evaluate combinations of novel agents or with standard chemotherapeutics or radiation therapy. We will emphasize the development and use of correlative biomarker and imaging approaches. Our ex- pertise in phase I clinical trial, large patient base, clinical infrastructure, and depth in basic and translational cancer biology and pharmacology will allow us to efficiently accomplish the goals of this proposal.

描述（由申请人提供）：本次UO 1 I期申请的总体目标是有效、安全地对NCI的新型抗癌药物进行剂量探索、药理学和生物标志物评价临床试验。I期研究的信息将指导进一步研究的最佳剂量和时间表的选择。大多数新的抗癌剂是基于机制的，具有有限的毒性，有限的单一药物活性，并且可能与其他疗法组合或在表达特定分子靶标的群体中最有效。为了成功开发这些药物，在将这些药物投入全面临床开发之前，必须提供证据证明这些药物击中了患者的预期分子靶点。 在临床开发早期，更好地了解这种效应与新药活性和毒性相关的生理后果也至关重要。我们提出以下具体目标：1.定义和描述药物的剂量限制性和非剂量限制性毒性，并提供临床活性的证据。2.确定新药的药代动力学特性，包括吸收、分布、代谢和消除。我们将评价这些参数对毒性、疗效和靶点抑制或刺激的药效学影响。3.评价新的生物标志物和/或成像研究，这些研究将为药物在目标水平的活性提供原理证明，并将其与其他临床和药代动力学/药效学终点相关联。4.根据所有可用的毒性、疗效、PK、PD、成像和生物标志物数据确定II期剂量。由于目前还不完全了解将在NCI管道中可用的新药，我们将把我们的方法集中在我们具有科学专业知识和生产性转化临床研究跟踪记录的药物类别上，包括1）靶向肿瘤血管生成的药物; 2）靶向肿瘤或肿瘤基质生长因子抑制的药物;和3）新型疫苗和其它免疫调节剂。我们还擅长研究针对脑肿瘤患者的I期药物。我们预计每年进行2-3项研究。我们将强调单一药物的研究，但也可以评估新药物的组合或与标准化疗或放射治疗。我们将强调相关生物标志物和成像方法的开发和使用。我们在I期临床试验、大型患者基础、临床基础设施方面的经验以及在基础和转化癌症生物学和药理学方面的深度将使我们能够有效地实现本提案的目标。