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:10603182
- 负责人:
- 金额:$ 0.16万
- 依托单位:
- 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 2023-05-31
- 项目状态:已结题
- 来源:
- 关键词:AdjuvantAdjuvant TherapyAdultAffectAlkylating AgentsAnimal ModelAnimalsBMX geneBlood - brain barrier anatomyBone MarrowBone Marrow SuppressionChemistryChemotherapy and/or radiationClinical TreatmentClinical TrialsCognitionCranial IrradiationDeteriorationDiagnosisDiffusion Magnetic Resonance ImagingDisease ProgressionDoseExcisionFormulationFundingGenetic TranscriptionGlioblastomaGliomaGoalsHippocampus (Brain)Howard Temin AwardHumanImpaired cognitionImpairmentIncidenceInvestmentsLeadLifeMetalloporphyrinsNervous System PhysiologyNeuraxisNewly DiagnosedNormal tissue morphologyNuclearOperative Surgical ProceduresOutcomeOxidation-ReductionPatientsPharmaceutical PreparationsPharmacologic SubstancePhasePhase I Clinical TrialsPhase II Clinical TrialsPlatelet Count measurementPrimary Brain NeoplasmsProgression-Free SurvivalsQuality of lifeRadiation InjuriesRadiation therapyRandomizedReactive Oxygen SpeciesReportingResistanceSeriesSerious Adverse EventSmall Business Innovation Research GrantStressTestingTherapeutic AgentsThrombocytopeniaTimeToxicologyUp-Regulationaggressive therapybasebrain magnetic resonance imagingbrain tissuecancer diagnosischemoradiationchemotherapycognitive functioncommercializationdrug qualityexperiencehealth related quality of lifeimprovedmouse modelneoplastic cellneurotoxicitynext generationnovel drug classopen labelphase I trialphase II trialpreclinical safetypreventprimary outcomeradiological imagingrare cancerresponsescale upside effectstability testingstandard of carestem cellstemozolomidetranscription factortreatment responsetumortumor growthwhite matterwhite matter damage
项目摘要
PROJECT SUMMARY/ABSTRACT
A randomized, proof-of-concept, Phase 2 clinical trial of a new class of redox-active pharmaceutical is
proposed in 160 subjects undergoing primary treatment for high-grade glioma (WHO grade III and IV).
Under a prior Phase II SBIR, a Phase 1 clinical trial has been completed with establishment of the
recommended dose being used for this Phase 2 clinical trial. This project will test a compound that, in
animals, has been demonstrated to cross the blood-brain barrier and prevent hippocampal stem cell loss
and white matter degradation following radiation therapy (RT). The compound also enhances tumor killing
in combination with radiation therapy and thus has the dual impact of protecting normal tissues while
improving tumor treatment responses. This drug is both neuroprotective against RT and 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 12-16 months after
diagnosis. Most high-grade gliomas are resistant to current available therapies. Thus, a major require-
ment for the next generation therapy of primary brain tumors is more effective tumor control, protection
against neurotoxicity, and reduction in the incidence of bone marrow suppression (i.e., thrombo-
cytopenia). The Phase 2 clinical trial proposed in this SBIR Phase IIB Bridge Award is to test the
hypothesis that BMX-001, the lead compound in a new class of redox-active metalloporphyrins, will
extend patient survival and at the same time protect normal tissues and enhance quality of life. The
specific aims are to: 1) confirm enhanced survival (tumor control) by completing a randomized, open-
label Phase 2 clinical trial of BMX-001 in combination with standard RT and TMZ in newly diagnosed
high-grade glioma patients (160 subjects, 1:1 randomization), and 2) confirm protection from side effects
of radiochemotherapy by assessing cognition, white matter integrity, quality of life (HRQoL) and bone
marrow protection. The primary outcomes are 1) Efficacy based on overall and progression-free survival;
2) Protection/improvement of cognition; 3) Radiographic response of tumor; and 4) Protection of bone
marrow against chemotherapy-induced thrombocytopenia. Exploratory outcomes are 1) HRQoL and
2) White matter integrity (MRI brain diffusion tensor imaging).
项目摘要/摘要
一种新型氧化还原活性药物的随机、概念验证、2期临床试验
建议在160名接受高级别胶质瘤初级治疗(世卫组织III级和IV级)的受试者中使用。
在先前的第二阶段SBIR下,第一阶段临床试验已经完成,并建立了
此二期临床试验使用的推荐剂量。该项目将测试一种化合物,在
动物,已被证明可以穿越血脑屏障,防止海马体干细胞丢失
和放射治疗(RT)后的脑白质退化。该化合物还能增强对肿瘤的杀伤力。
与放射治疗相结合,具有保护正常组织的双重效果
提高肿瘤治疗反应。这种药物对RT既有神经保护作用,也有望
RT增强对胶质母细胞瘤的抑制作用。原发脑瘤占所有确诊癌症的1%。
尽管这些肿瘤是一种罕见的恶性肿瘤,但高级别胶质瘤具有侵袭性和致命性。
与严重致残的中枢神经系统相关。认知与神经学
在诊断和治疗过程中,功能会受到损害。新诊断病例的护理标准
高级别胶质瘤需要手术切除,然后同步应用替莫唑胺(TMZ)进行放疗。
尽管进行了积极的治疗,但几乎所有患有最常见的成人原发脑瘤的患者,
胶质母细胞瘤(WHO IV级),死于疾病进展;中位生存期为12-16个月
诊断。大多数高级别胶质瘤对目前可用的治疗方法都有抵抗力。因此,一项主要要求是-
为下一代治疗原发性脑肿瘤提供更有效的肿瘤控制、保护
抗神经毒性,减少骨髓抑制(即血栓形成)的发生率。
细胞减少症)。在这个SBIR阶段IIB桥奖中提出的第二阶段临床试验是为了测试
假设一类新的氧化还原活性金属卟啉中的先导化合物BMX-001将
延长患者生存时间,同时保护正常组织,提高生活质量。这个
具体目标是:1)通过完成一项随机的、开放的-
BMX-001联合标准RT和TMZ治疗初诊患者的LABELⅡ期临床试验
高级别胶质瘤患者(160名受试者,1:1随机),以及2)证实了副作用的保护
通过评估认知、白质完整性、生活质量(HRQOL)和骨骼来评估放化疗
保护骨髓。主要结果是:1)基于总生存率和无进展生存率的疗效;
2)保护/改善认知;3)肿瘤的放射反应;4)保护骨骼
骨髓抗化疗引起的血小板减少症。探索性结果是1)HRQOL和
2)脑白质完整性(MRI脑扩散张量成像)。
项目成果
期刊论文数量(0)
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- 批准号:
10974166 - 财政年份:2023
- 资助金额:
$ 0.16万 - 项目类别:
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
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9145170 - 财政年份:2015
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$ 0.16万 - 项目类别:
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
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