In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. TPS2577-TPS2577
Abstract:
TPS2577 Background: Patients diagnosed with malignant high-grade gliomas (WHO grade III-IV) experience significant morbidity and mortality associated with these cancers. While the mainstay of therapy for patients with newly diagnosed high-grade glioma is surgery followed by concurrent chemotherapy and radiation therapy (RT), the outcomes remain very poor. BMX-001 (MnTnBuOE-2-PyP 5+ ) is a metalloporphyrin with differential action in response to radiation therapy and chemotherapy-induced oxidative stress. Early preclinical studies demonstrated BMX-001’s ability to act as a radioprotectant to healthy tissue such as a central nervous white matter and as a radiosensitizer to cancer cells, in particular, human glioblastoma xenografts. We evaluated the safety of BMX-001 in combination with concurrent RT and temozolomide (TMZ) in a phase I study of newly diagnosed high-grade glioma patients, and we found that BMX-001 is safe and well-tolerated in this population. The maximum tolerated dose of BMX-001 during concurrent RT and TMZ was determined to be 28 mg delivered subcutaneously (SC) followed by 16 biweekly SC doses at 14 mg (Peters et al., Neuro-Oncology 2018). Methods: For this multi-site, open-label, phase II study (NCT02655601), we will randomize approximately 160 patients 1:1 to concurrent RT and TMZ with BMX-001 versus concurrent RT and TMZ alone. Key eligibility criteria include newly diagnosed histologically confirmed high-grade glioma (WHO III-IV), 18 ≥ years, and Karnofsky performance status ≥ 70%. The primary endpoint is overall survival. Secondary endpoints include cognitive performance as assessed by standardized cognitive testing, bone marrow protection, safety and tolerability, progression-free survival, overall tumor response rate, and plasma pharmacokinetics. Exploratory endpoints are health-related quality of life (as assessed by Functional Assessment of Cancer Therapy–Brain, Functional Assessment of Cancer Therapy-Cognition, and Functional Assessment of Chronic Illness Therapy-Fatigue), qualitative hair loss, and white matter integrity (as measured by MRI diffusion tensor/susceptibility imaging). Since November 2018, this phase II study has enrolled 64 of 160 high-grade glioma patients at six sites with future sites planned to be implemented. Clinical trial information: NCT02655601 .
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2020.38.15_suppl.TPS2577
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2020
detail.hit.zdb_id:
2005181-5
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