Phase 0-1 Clinical Trials

0-1期临床试验

• 批准号: 10926123
• 负责人: James Doroshow
• 金额: $ 62.79万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10926123
• 关键词: Biological Assay; Biopsy; CCR; Clinical Trials; Collaborations; Combination immunotherapy; DNA Damage; DNA Double Strand Break; Development; Developmental Therapeutics Program; Division of Cancer Treatment and Diagnosis; Enzyme-Linked Immunosorbent Assay; Gamma-H2AX; Goals; Immunofluorescence Immunologic; MEKs; Molecular; New Agents; Pediatric Oncology; Pharmacodynamics; Pharmacology; Phase; Poly(ADP-ribose) Polymerases; Protein Isoforms; Proto-Oncogene Proteins c-akt; Series; System; Therapeutic Agents; Tumor Tissue; Type I DNA Topoisomerases; United States National Institutes of Health; clinical center; clinical development; detector; first-in-human; inhibitor; insight; novel; novel anticancer drug; novel therapeutics; pharmacologic; rapid diagnosis; rare cancer

The collaboration between the DTB and DCTD has been responsible for the development of several new pharmacodynamic assays, including an ultrasensitive immunofluorescence assay for gamma H2AX (DNA double strand break detector) in tumor tissue biopsies, and ELISAs for topoisomerase I and poly ADP-ribose polymerase (PARP), as well as assays for other DNA damage markers (pNBS1), all of the isoforms of MEK, ERK, and AKT, DNMTs, as well as a series of immuno-PD markers. These assays have been essential for first in human clinical trials of novel non-camptothecin topoismerase I inhibitors, DNMT1 inibitors, and immunotherapy combinations that have been activated in the NIH Clinical Center. In addition, collaborations with the Pediatric Oncology Branch have facilitated the development of new agents used for rare tumors. Additional collaborations have developed around our use of the NCI 60 for systems pharmacology.

DTB和DCTD之间的合作负责开发几种新的药效学测定，包括γ H2 AX的超灵敏免疫荧光测定（DNA双链断裂检测器），拓扑异构酶I和聚ADP-核糖聚合酶（PARP）的ELISA，以及其它DNA损伤标志物（pNBS 1）的测定，MEK、ERK和AKT的所有同种型，DNMT，以及一系列免疫PD标志物。这些检测对于NIH临床中心已激活的新型非喜树碱拓扑异构酶I抑制剂、DNMT 1抑制剂和免疫治疗组合的首次人体临床试验至关重要。此外，与儿科肿瘤学分支的合作促进了用于罕见肿瘤的新药的开发。围绕我们使用NCI 60进行系统药理学研究，还开展了其他合作。

项目成果

Pharmacodynamic endpoints as clinical trial objectives to answer important questions in oncology drug development.

• DOI: 10.1053/j.seminoncol.2016.07.002
• 发表时间: 2016-08
• 期刊: Seminars in oncology
• 影响因子: 4
• 作者: Parchment RE;Doroshow JH
• 通讯作者: Doroshow JH

Phase I study of the heat shock protein 90 (Hsp90) inhibitor onalespib (AT13387) administered on a daily for 2 consecutive days per week dosing schedule in patients with advanced solid tumors.

热休克蛋白90（HSP90）抑制剂ONALESPIB（AT13387）的I期研究每天在晚期实体瘤患者中每周连续2天给药。

• DOI: 10.1007/s10637-015-0255-1
• 发表时间: 2015-08
• 期刊: Investigational new drugs
• 影响因子: 3.4
• 作者: Do K;Speranza G;Chang LC;Polley EC;Bishop R;Zhu W;Trepel JB;Lee S;Lee MJ;Kinders RJ;Phillips L;Collins J;Lyons J;Jeong W;Antony R;Chen AP;Neckers L;Doroshow JH;Kummar S
• 通讯作者: Kummar S

Exposure time versus cytotoxicity for anticancer agents.

暴露时间与抗癌药的细胞毒性。

• DOI: 10.1007/s00280-019-03863-w
• 发表时间: 2019-08
• 期刊: Cancer chemotherapy and pharmacology
• 影响因子: 3
• 作者: Evans DM;Fang J;Silvers T;Delosh R;Laudeman J;Ogle C;Reinhart R;Selby M;Bowles L;Connelly J;Harris E;Krushkal J;Rubinstein L;Doroshow JH;Teicher BA
• 通讯作者: Teicher BA

A Phase I Study of Ganetespib and Ziv-Aflibercept in Patients with Advanced Carcinomas and Sarcomas.

• DOI: 10.1634/theoncologist.2018-0203
• 发表时间: 2018-11
• 期刊: The oncologist
• 作者: Meehan R;Kummar S;Do K;O'Sullivan Coyne G;Juwara L;Zlott J;Rubinstein L;Doroshow JH;Chen AP
• 通讯作者: Chen AP

Collaborating to Move Research Forward: Proceedings of the 10th Annual Bladder Cancer Think Tank.

• DOI: 10.3233/blc-169007
• 发表时间: 2016-04-27
• 期刊: Bladder cancer (Amsterdam, Netherlands)
• 作者: Kamat AM;Agarwal P;Bivalacqua T;Chisolm S;Daneshmand S;Doroshow JH;Efstathiou JA;Galsky M;Iyer G;Kassouf W;Shah J;Taylor J;Williams SB;Quale DZ;Rosenberg JE
• 通讯作者: Rosenberg JE