A Phase I trial of cancer-targeting micelles for non-myoinvasive bladder cancer

癌症靶向胶束治疗非肌浸润性膀胱癌的 I 期试验

基本信息

批准号：
10426035
负责人：
CHONG-XIAN PAN
金额：
--
依托单位：
VA BOSTON HEALTH CARE SYSTEM
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-10-01 至 2024-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10426035
关键词：
Address Amino Acid Sequence BCG Live Binding Biopsy Biopsy Specimen Bladder Blood Cells Cancer Patient Canis familiaris Cells Chemistry Clinical Research Clinical Trials Clinical Trials Design Common Terminology Criteria for Adverse Events Conduct Clinical Trials Consultations Correlative Study Cyclic GMP Cystoscopy Cytology Data Diagnosis Disease Progression Dose Drug Delivery Systems Drug Targeting Fibroblasts Funding Future Goals Grant Hour Human In Vitro Inflammation Intravesical Instillation Investigational New Drug Application K-Series Research Career Programs Ligands Malignant Neoplasms Malignant neoplasm of urinary bladder Maximum Tolerated Dose Measures Medical Methods Micelles Minor Molecular Names Newly Diagnosed Paclitaxel Patient Care Patients Pharmaceutical Preparations Pharmacology and Toxicology Phase Phase I Clinical Trials Published Comment Radical Cystectomy Recurrence Refractory Reporting Research Design Resources Safety Sample Size Secondary to Specificity Surface Therapeutic Agents Toxic effect Transurethral Resection Treatment outcome United States United States Food and Drug Administration Urine Urothelial Cell Vascular Endothelial Cell absorption arm base cancer cell cancer diagnosis cancer recurrence cell killing cohort cost effective therapy first-in-human improved in vivo intravesical nanomicelles nanoscale non-muscle invasive bladder cancer novel open label patient population pembrolizumab phase I trial prevent recruit response study population systemic toxicity tumor progression

项目摘要

The goal of this project is to conduct a Phase I clinical trial to determine the recommended Phase II dose (RP2D) of bladder cancer-targeting micelles loaded with a chemotherapeutic drug paclitaxel (PTX). With a VA Career Development Award-2 and VA Merit grant (PI: Pan), we developed a bladder cancer-specific targeting ligand named PLZ4, and a PLZ4-coated PTX-loaded nanoscale micelle (PPM) platform that can specifically deliver the drug load into bladder cancer cells both in vitro and in vivo. This proposed clinical trial is to conduct a first-in-human trial to use PPM for the treatment of non-myoinvasive bladder cancer (NMIBC). Bladder cancer is one of the ten most common cancers in the United States. NMIBC accounts for around 75% of bladder cancer cases at diagnosis. The current first-line treatment approach of transurethral resection followed by intravesical instillation of therapeutic agents, usually Bacillus Calmette-Guérin (BCG), is associated with a recurrence rate of around 70% at two years. Pembrolizumab and valrubicin are the only second-line drug approved by the Food and Drug Administration (FDA) with a response rate of 40% and 20-40%, respectively. Considering that bladder cancer is among the top ten most common cancers and over 70% of bladder cancers are diagnosed as NMIBC, there are huge unmet medical needs for developing more effective therapies. This primary objective of the proposed Phase I trial is to determine the recommended Phase II dose (RP2D) of PPM. The secondary objectives are to assess the toxicity, obtain preliminary efficacy information of PPM, and determine systemic absorption after intravesical instillation of PPM. Up to 25 patients with recurrent or refractory NMIBC after a standard first-line intravesical therapy pembrolizumab treatment will be recruited. PPM will be given as intravesical instillation once weekly for six weeks. The toxicity will be assessed by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The efficacy will be determined by urine cytology and cystoscopy two weeks after finishing treatment. Molecular correlative studies will be performed.

该项目的目的是进行I期临床试验以确定建议的II期剂量（rp2d）的（RP2D）含有化学治疗药物紫杉醇（PTX）的为癌靶向胶束。与VA 职业发展奖2和VA优异授予赠款（PI：PAN），我们开发了膀胱特定的靶向目标名为PLZ4的配体，以及可以专门的PLZ4涂层PTX纳米级胶束（PPM）平台在体外和体内将药物负荷输送到膀胱癌细胞中。该拟议的临床试验是进行人类的第一个使用PPM治疗非肿瘤性膀胱癌（NMIBC）的试验。是美国十个最常见的癌症之一。 NMIBC约占膀胱的75％诊断时的癌症病例。尿道切除的当前一线治疗方法，然后是静脉注入治疗剂，通常是Calmetteguérin（BCG），与两年后的复发率约为70％。 pembrolizumab和valrubicin是唯一的二线药物得到食品药品监督管理局（FDA）的批准，响应率分别为40％和20-40％。考虑到膀胱癌是十大最常见的癌症之一，超过70％的膀胱癌被诊断为NMIBC，有巨大的未满足医疗需求来开发更有效的疗法。这拟议I期试验的主要目标是确定PPM的建议II期剂量（RP2D）。次要目标是评估毒性，获得PPM的初步效率信息，并确定静脉内滴注PPM后的全身性滥用。多达25例复发或难治的患者 NMIBC将招募标准的一线静脉治疗Pembrolizumab治疗后。 PPM将是每周六周一次作为静脉输出滴注。毒性将由NCI共同评估不良事件的术语标准（CTCAE）版本5.0。效率将由尿液细胞学确定完成治疗后两周和膀胱镜检查。将进行分子相关研究。