BMX-001 as a Therapeutic Agent for Treatment of High-Grade Gliomas

BMX-001 作为治疗高级别胶质瘤的治疗剂

基本信息

批准号：
8904217
负责人：
James D Crapo
金额：
$ 97.64万
依托单位：
BIOMIMETIX JV, LLC
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-18 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8904217
关键词：
Adjuvant Adult Affect BMX gene Blood - brain barrier anatomy Brain Brain Neoplasms Cancer Patient Chemistry Clinical Trials Cognition Cranial Irradiation Deterioration Diagnosis Diffusion Magnetic Resonance Imaging Disease Progression Dose Drug Formulations Drug Kinetics Excision Glioblastoma Glioma Goals Hair Hippocampus (Brain)Human Impaired cognition Impairment Investments Joint Ventures Magnetic Resonance Imaging Malignant Neoplasms Manganese Maximum Tolerated Dose Metalloporphyrins Nervous System Physiology Nervous system structure Neuraxis Newly Diagnosed Normal tissue morphology Nuclear Operative Surgical Procedures Outcome Oxidation-Reduction Oxidative Stress Pathway interactions Patients Pharmaceutical Preparations Pharmacologic Substance Phase Phase I Clinical Trials Phase II Clinical Trials Primary Brain Neoplasms Progression-Free Survivals Radiation Radiation induced damage Radiation therapy Radiation-Sensitizing Agents Radio Randomized Reactive Oxygen Species Resistance Safety Series Small Business Innovation Research Grant Stem cells Stress Testing Therapeutic Therapeutic Agents Toxicology Treatment Protocols Up-Regulation base brain tissue cancer diagnosis chemotherapy drug quality health related quality of life human subject improved killings neurotoxicity next generation open label preclinical safety preclinical study prevent primary outcome public health relevance response scale up secondary outcome stability testing standard of care temozolomide transcription factor treatment response tumor white matter white matter damage

项目摘要

DESCRIPTION (provided by applicant): Phase 1 and Phase 2 clinical trials of a new class of redox-active pharmaceutical are proposed in high-grade glioma (WHO grade III and IV). This project will test a compound that crosses the blood-brain barrier and which prevents hippocampal stem cell loss and white matter degradation following radiation therapy (RT). The compound also inhibits tumor regrowth following RT and thus has the dual impact of protecting normal tissues while improving tumor treatment responses. This drug is both neuroprotective against RT and a radio sensitizer that is expected to enhance inhibition of glioblastoma by RT. Primary brain tumors represent 1% of all diagnosed cancers. Even though these tumors represent a rare malignancy, high-grade gliomas are aggressive and lethal and are associated with severe disabling central nervous system involvement. Cognition and neurological function are compromised at diagnosis and during treatment. The standard of care for newly diagnosed high-grade gliomas involves surgical resection, followed by RT with concurrent temozolomide (TMZ). Despite aggressive treatment, nearly all patients with the most common form of adult primary brain tumor, glioblastoma (WHO grade IV), die of disease progression; median survival is 9-15 months after diagnosis. Most high-grade gliomas are resistant to current available therapies. Thus, a major requirement for the next generation therapy of primary brain tumors requires more effective tumor control and protection against the neurotoxicity. The objective of this proposed project is to test the hypothesis that a new class of redox-active metalloporphyrins is an effective radio protector and tumor sensitizer in brain tissue. The specific aims are to: 1) perform a Phase 1 clinical trial of this new drug in combination with standard RT and TMZ in newly diagnosed high-grade glioma patients, and 2) perform a randomized open-label Phase 2 clinical trial of the new drug in combination with standard RT and TMZ versus standard RT and TMZ alone in patients with newly diagnosed high-grade glioma patients. The primary outcome is protection/improvement of cognition. This new class of drug has the potential to protect against deterioration of cognition and improve health-related quality of life in high-grade glioma patients undergoing RT and chemotherapy, while also enhancing patient survival.

描述（通过应用程序提供）：在高级神经胶质瘤（WHO III和IV级）中提出了新的氧化还原活性药物类药物的阶段和第2阶段临床试验。该项目将测试横穿血脑屏障的化合物，并防止放射治疗后海马干细胞损失和白质降解。该化合物还抑制了RT后的肿瘤后悔，因此具有保护正常组织的双重影响，同时改善了肿瘤治疗反应。该药物既是针对RT的神经保护性，又是无线电传感器，预计将通过RT增强胶质母细胞瘤的抑制作用。原发性脑肿瘤占所有被诊断的癌症的1％。即使这些肿瘤代表了罕见的恶性肿瘤，但高级神经胶质瘤还是侵略性和致命性的，并且与严重的残疾中枢神经系统受累有关。认知和神经功能新诊断的高级神经胶质瘤的护理标准涉及手术切除，其次是与替莫唑胺（TMZ）的RT。尽管有积极的治疗，但几乎所有具有成年原发性脑肿瘤，胶质母细胞瘤（IV级）的最常见形式的患者死于疾病进展。诊断后9-15个月的中位数生存期。大多数高级神经胶质瘤对当前可用疗法具有抗性。这是对原发性脑肿瘤的下一代治疗的主要要求，需要更有效的肿瘤控制和保护神经毒性。该提出的项目的目的是检验以下假设：新的氧化还原活性金属甲丁物是脑组织中有效的无线电保护剂和肿瘤传感器。具体目的是：1）在新诊断的高级神经胶质瘤患者中与标准RT和TMZ一起进行该新药的1期临床试验，以及2）2）2）进行新药的随机开放标签2期临床试验，并与标准RT和TMZ相结合，与新诊断的高级诊断患者的标准RT和TMZ相结合。主要结果是对认知的保护/改善。这种新的药物有可能防止认知恶化并改善与健康相关的高度神经胶质瘤患者的生活质量接受RT和化学疗法，同时还可以增强患者的生存。