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).
项目总结/摘要
一项关于一类新的氧化还原活性药物的随机、概念验证、2期临床试验,
在160例接受高级别胶质瘤(WHO III级和IV级)初级治疗的受试者中提出。
根据之前的II期SBIR,已经完成了1期临床试验,
本II期临床试验使用的推荐剂量。该项目将测试一种化合物,
动物,已被证明可以穿过血脑屏障并防止海马干细胞丢失
和放射治疗(RT)后的白色物质降解。该化合物还能增强肿瘤杀伤力
并因此具有保护正常组织的双重作用,
改善肿瘤治疗反应。这种药物对RT具有神经保护作用,
通过RT增强胶质母细胞瘤的抑制。原发性脑肿瘤占所有诊断癌症的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
并且与严重的中枢神经系统损伤有关。认知和神经
功能在诊断和治疗过程中受到损害。新诊断的标准治疗
高级别神经胶质瘤涉及手术切除,然后进行RT和同时进行替莫唑胺(TMZ)。
尽管进行了积极的治疗,但几乎所有最常见的成人原发性脑肿瘤患者,
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.大多数高级别神经胶质瘤对目前可用的疗法具有抗性。因此,一个主要的要求-
下一代肿瘤治疗方案对原发性脑肿瘤更有效的控制、保护
抗神经毒性,和降低骨髓抑制的发生率(即,血栓,血栓
血细胞减少症)。SBIR Phase IIB Bridge Award中提出的2期临床试验旨在测试
假设BMX-001(一类新的氧化还原活性金属卟啉中的先导化合物)将
延长患者生存期,同时保护正常组织并提高生活质量。的
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治疗新诊断糖尿病患者的标签2期临床试验
高级别胶质瘤患者(160名受试者,1:1随机化),和2)证实了对副作用的保护
通过评估认知、白色物质完整性、生活质量(HRQoL)和骨
骨髓保护主要结局是1)基于总体和无进展生存期的疗效;
2)保护/改善认知; 3)肿瘤的放射学反应;和4)保护骨
骨髓对抗化疗引起的血小板减少症。探索性结局为1)HRQoL和
2)白色物质完整性(MRI脑扩散张量成像)。
项目成果
期刊论文数量(0)
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{{ truncateString('James D Crapo', 18)}}的其他基金
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- 批准号:
10974167 - 财政年份:2023
- 资助金额:
$ 0.16万 - 项目类别:
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COPD 的遗传流行病学(COPD 基因) 任务 A:研究访问 4、收集 COPDGENE 研究数据和生物样本以及 COPDGENE 研究的监督
- 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
- 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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8904217 - 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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