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

以 1 期为重点的新型抗癌药物的早期临床试验 (U01)

• 批准号: 8628939
• 负责人: GLENN LIU
• 金额: $ 60.37万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-02-27 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8628939
• 关键词: Address; Antineoplastic Agents; Basic Science; Cancer Therapy Evaluation Program; Clinical; Clinical Investigator; Clinical Research; Clinical Trials; Comprehensive Cancer Center; Correlative Study; Data; Development; Discipline; Dose; Drug Interactions; Drug Kinetics; Evaluation; Evolution; Foundations; Funding; Future; Goals; Grant; Investigation; Malignant Neoplasms; Methods; Nature; New Agents; Patients; Pharmaceutical Preparations; Phase; Phase I Clinical Trials; Phase I/II Trial; Play; Research Infrastructure; Role; Schedule; Testing; Therapeutic; Treatment Protocols; United States National Institutes of Health; Universities; Wisconsin; active method; cancer care; cytotoxic; design; drug development; expectation; experience; innovation; meetings; named group; novel; oncology; pre-clinical research; programs; trend

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.

描述（由申请人提供）：自 1979 年以来，威斯康星大学 Paul P. Carbone 综合癌症中心 (UWCCC) 的 I 期项目一直在 NCI 资助下进行高质量的 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体化癌症护理的标准奠定了基础。此申请代表 U01 CA062491 的更新。我们的第一阶段计划继续强调 1979 年建立的临床试验的卓越传统，并承诺：1）支持 UWCCC 正在进行的各种临床前研究； 2）提供专门用于临床研究的稳定基础设施； 3）维持一支优秀的临床研究者队伍，进行高质量的试验； 4) 促进整个 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由 NCI 资助的药物开发研究的经验，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：进行有针对性的早期临床试验 目标 2：评估药代动力学以确定剂量、时间表、暴露和效果关系 目标 3：探索新药物评估的新范式和设计 目标 4：在早期临床试验中研究特殊人群 目标 5：为新药物建立安全且具有生物活性的治疗方案 目标 6：确定新分子靶向药物原理数据的机械证明 目标 7：评估 CTEP IND 药物的组合评估药物-药物相互作用的性质 目标 8：评估研究药物临床试验中的转化终点 UWCCC 每年平均有 535 名患者进入早期临床试验（I 期和 II 期），其中 225 名患者处于第二阶段我试炼。这种早期临床试验累积的良好记录确保了 I 期项目有能力满足每年 50 名患者的 CTEP U01 累积预期。在当前资助期内，第一阶段计划实现了上述所有目标，每年平均有 54 名患者参与批准的 U01 早期临床试验。虽然所有 I 期计划 UO1 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。

项目成果

Amongst eligible patients, age and comorbidity do not predict for dose-limiting toxicity from phase I chemotherapy.

在符合条件的患者中，年龄和合并症并不能预测 I 期化疗的剂量限制性毒性。

• 发表时间: 2010-03
• 影响因子: 3
• 作者: LoConte, Noelle K;Smith, Maureen;Alberti, Dona;Bozeman, Jeffrey;Cleary, James F;Setala, Ashley N;Wodtke, Geoff;Wilding, George;Holen, Kyle D
• 通讯作者: Holen, Kyle D

Phase I and pharmacokinetic study of the novel redox-active agent, motexafin gadolinium, with concurrent radiation therapy in patients with locally advanced pancreatic or biliary cancers.

新型氧化还原活性剂莫泰沙芬钆与局部晚期胰腺癌或胆道癌患者同步放射治疗的 I 期和药代动力学研究。

• 发表时间: 2006-04
• 影响因子: 3
• 作者: Ramanathan, Ramesh K;Fakih, Marwan;Mani, Sridhar;Deutsch, Melvin;Perez, Raymond P;Ritter, Mark A;Eiseman, Julie L;Ivy, S Percy;Trump, Donald L;Belani, Chandra P;Parise, Robert A;Potter, Douglas M;Egorin, Merrill J
• 通讯作者: Egorin, Merrill J

Oxaliplatin pharmacokinetics and pharmacodynamics in adult cancer patients with impaired renal function.

肾功能受损的成年癌症患者中奥沙利铂的药代动力学和药效学。

• 发表时间: 2007-08-15
• 作者: Takimoto, Chris H;Graham, Martin A;Lockwood, Graham;Ng, Chee M;Goetz, Andrew;Greenslade, Dennis;Remick, Scot C;Sharma, Sunil;Mani, Sridhar;Ramanathan, Ramesh K;Synold, Timothy W;Doroshow, James H;Hamilton, Anne;Mulkerin, Daniel L;Ivy, Percy
• 通讯作者: Ivy, Percy

Dose-escalating and pharmacological study of bortezomib in adult cancer patients with impaired renal function: a National Cancer Institute Organ Dysfunction Working Group Study.

硼替佐米在肾功能受损的成年癌症患者中的剂量递增和药理学研究：国家癌症研究所器官功能障碍工作组研究。

• 发表时间: 2011-12
• 影响因子: 3
• 作者: Leal, Ticiana B;Remick, Scot C;Takimoto, Chris H;Ramanathan, Ramesh K;Davies, Angela;Egorin, Merrill J;Hamilton, Anne;LoRusso, Patricia A;Shibata, Stephen;Lenz, Heinz;Mier, James;Sarantopoulos, John;Mani, Sridhar;Wright, John J;Ivy, S
• 通讯作者: Ivy, S

A phase I trial of perifosine (NSC 639966) on a loading dose/maintenance dose schedule in patients with advanced cancer.

对晚期癌症患者进行负荷剂量/维持剂量方案的哌立福辛 (NSC 639966) 的 I 期试验。

• 发表时间: 2004-11-15
• 作者: Van Ummersen, Lynn;Binger, Kim;Volkman, Jennifer;Marnocha, Rebecca;Tutsch, Kendra;Kolesar, Jill;Arzoomanian, Rhoda;Alberti, Dona;Wilding, George
• 通讯作者: Wilding, George