Early Clinical Trials of New Anti-Cancer Agents with Phase 1 Emphasis (U01)

描述（由申请人提供）：自1979年以来，威斯康星州大学Paul P. Carbone综合癌症中心（UWCCC）的I期项目一直在进行由NCI赞助的高质量I期药物开发研究。因此，我们在早期药物开发的演变中发挥了积极作用，并为帮助制定未来个性化癌症护理的标准奠定了基础。本申请代表U 01 CA 062491的更新。我们的I期项目继续强调1979年建立的卓越临床试验传统，承诺：1）支持UWCCC进行的各种临床前研究; 2）提供稳定的临床研究基础设施; 3）保持一支优秀的临床研究人员队伍，他们进行高质量的试验; 4）促进UWCCC和校园内专家之间的互动。本申请详细介绍了我们在上一个资助期内在NCI申办的药物开发研究中的经验，并描述了我们进行这些研究的方法。我们当前和未来的目标是：目标1：开展靶向早期临床试验目标2：评估药代动力学，以建立剂量、给药方案、暴露和效应关系目标3：探索新药评价的新范式和设计目标4：研究早期临床试验中的特殊人群目标5：为新药建立安全和生物活性的治疗方案目的6：确定新分子靶向药物的原理数据的机制证据目的7：评价CTEP IND药物的组合，以评估药物相互作用的性质目的8：UWCCC每年平均有535名患者参加早期临床试验（I期和II期），其中225名患者参加I期试验。早期临床试验累积的良好记录确保I期项目有能力满足CTEP U 01每年50例患者的累积预期。在目前的资助期内，I期项目实现了上述所有目标，每年平均有54名患者参加U 01早期临床试验。虽然所有I期项目UO 1试验都有转化终点，但其中7项试验的相关研究获得了CTEP-TRI资助。

DESCRIPTION (provided by applicant): The Phase I Program of the University of Wisconsin Paul P. Carbone Comprehensive Cancer Center (UWCCC) has been consistently performing high quality phase I drug development studies sponsored by the NCI since 1979. As a result, we have played an active role in the evolution of early drug development and built the foundation to help set the standard for the delivery of individualized cancer care in the future. This application represents the renewal of U01 CA062491. Our Phase I Program continues to emphasize the tradition of excellence in clinical trials established in 1979 with a commitment to: 1) support the diverse array of preclinical research being performed at the UWCCC; 2) provide a stable infrastructure devoted to clinical research; 3) maintain an outstanding group of clinical investigators who perform high quality trials; and 4) promote the interactions between experts throughout the UWCCC and campus. This application details our experience in NCI-sponsored drug development studies over the last grant period and also describes the methods by which we performed these studies. Our current and future objectives are: Objective 1: Conduct of targeted early phase clinical trials Objective 2: Assessment of pharmacokinetics to establish dose, schedule, exposure and effect relationships Objective 3: Explore novel paradigms and designs for the evaluation of new agents Objective 4: Study special populations in early phase clinical trial Objective 5: Establish safe and biologically active treatment schedules for novel agents Objective 6: Determine mechanistic proof of principle data for new molecularly targeted agents Objective 7: Evaluate combinations of CTEP IND agents to assess the nature of drug-drug interactions Objective 8: Evaluation of translational endpoints in clinical trials of investigational agents The UWCCC accrues an average of 535 patients per year to early-phase clinical trials (phase I and II), of which 225 are on phase I trials. This strong track record for early-phase clinical trials accrual assures that the Phase I Program has the capability to meet CTEP U01 accrual expectations of 50 patients per year. During the current grant period, the Phase I Program addressed all of the objectives noted above and accrued an average of 54 patients to approved U01 early phase clinical trials annually. While all Phase I Program UO1 trials had translational endpoints, correlative studies of seven of these trials received CTEP-TRI funding.