دورية أكاديمية
A multicenter, phase 1, Adult Brain Tumor Consortium trial of oral terameprocol for patients with recurrent high-grade glioma (GATOR).
| العنوان: | A multicenter, phase 1, Adult Brain Tumor Consortium trial of oral terameprocol for patients with recurrent high-grade glioma (GATOR). |
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| المؤلفون: | Ahluwalia MS; Rose and Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH, USA; Miami Cancer Institute, Baptist Health South Florida, Miami, FL, USA. Electronic address: manmeeta@baptisthealth.net., Ozair A; Miami Cancer Institute, Baptist Health South Florida, Miami, FL, USA; Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA., Rudek M; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Ye X; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Holdhoff M; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Lieberman FS; Department of Neurology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Piotrowski AF; Department of Neuro-Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Nabors B; Department of Neurology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA., Desai A; Department of Neurology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA., Lesser G; Department of Hematology and Oncology, Wake Forest Medical Center, Winston, NC, USA., Huang RC; Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, MD, USA., Glenn S; Independent Consultant to Erimos Pharmaceuticals, Houston, TX, USA., Khosla AA; Miami Cancer Institute, Baptist Health South Florida, Miami, FL, USA., Peereboom DM; Rose and Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH, USA., Wen PY; Department of Neurology, Harvard Medical School, Boston, MA, USA; Center for Neuro-Oncology, Dana Farber Cancer Institute, Boston, MA, USA., Grossman SA; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD, USA. |
| المصدر: | Cell reports. Medicine [Cell Rep Med] 2024 Jul 16; Vol. 5 (7), pp. 101630. Date of Electronic Publication: 2024 Jul 01. |
| نوع المنشور: | Journal Article; Clinical Trial, Phase I; Multicenter Study |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101766894 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2666-3791 (Electronic) Linking ISSN: 26663791 NLM ISO Abbreviation: Cell Rep Med Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Cambridge, MA] : Cell Press, [2020]- |
| مواضيع طبية MeSH: | Glioma*/drug therapy , Glioma*/pathology , Brain Neoplasms*/drug therapy , Brain Neoplasms*/pathology, Humans ; Male ; Middle Aged ; Adult ; Female ; Aged ; Administration, Oral ; Aged, 80 and over ; Neoplasm Recurrence, Local/drug therapy ; Neoplasm Recurrence, Local/pathology ; Neoplasm Grading ; Maximum Tolerated Dose |
| مستخلص: | Recurrent high-grade gliomas (rHGGs) have a dismal prognosis, where the maximum tolerated dose (MTD) of IV terameprocol (5 days/month), a transcriptional inhibitor of specificity protein 1 (Sp1)-regulated proteins, is 1,700 mg/day with median area under the plasma concentration-time curve (AUC) of 31.3 μg∗h/mL. Given potentially increased efficacy with sustained systemic exposure and challenging logistics of daily IV therapy, here we investigate oral terameprocol for rHGGs in a multicenter, phase 1 trial (GATOR). Using a 3 + 3 dose-escalation design, we enroll 20 patients, with median age 60 years (range 31-80), 70% male, and median one relapse (range 1-3). Fasting patients tolerate 1,200 mg/day (n = 3), 2,400 mg/day (n = 6), 3,600 mg/day (n = 3), and 6,000 mg/day (n = 2) oral doses without major toxicities. However, increased dosage does not lead to increased systemic exposure, including in fed state (6,000 mg/day, n = 4), with maximal AUC <5 μg∗h/mL. These findings warrant trials investigating approaches that provide sustained systemic levels of transcription inhibitors to exploit their therapeutic potential. This study was registered at ClinicalTrials.gov (NCT02575794). Competing Interests: Declaration of interests M.S.A. – grants: Seagen, AstraZeneca, BMS, Bayer, Incyte, Pharmacyclics, Novocure, MimiVax, and Merck. Consultation fees: Bayer, Novocure, Kiyatec, Insightec, GSK, Xoft, Nuvation, Celularity, SDP Oncology, Apollomics, Prelude Therapeutics, Janssen, Tocagen, Voyager Therapeutics, ViewRay, Caris Life Sciences, Pyramid Biosciences, Varian Medical Systems, Cairn Therapeutics, AnHeart Therapeutics, Menarini Ricerche, Sumitomo Pharma Oncology, Autem therapeutics, GT Medical Technologies, Allovir, Equillium Bio., QV Bioelectronics, and Theraguix. Scientific Advisory Board memberships: Cairn Therapeutics, Pyramid Biosciences, Bugworks, and Modifi Biosciences. Data Safety and Monitoring Committee membership: VBI Vaccines. Stock shareholder: MimiVax, CytoDyn, Trisalus Lifesciences, and MedInnovate Advisors, LLC. D.M.P. – consulting or advisory role: Orbus Therapeutics, Sumitomo Dainippon Pharma Oncology, Inc., Stemline Therapeutics, and Novocure. Research funding: Pfizer (Inst), Novartis (Inst), NeOnc Technologies (Inst), Orbus Therapeutics (Inst), Bristol Myers Squibb (Inst), Genentech/Roche (Inst), Pharmacyclics (Inst), Bayer (Inst), Karyopharm Therapeutics (Inst), Apollomics (Inst), Vigeo Therapeutics (Inst), Global Coalition for Adaptive Research (Inst), MimiVax (Inst), Ono Pharmaceutical (Inst), and Mylan (Inst). Equity ownership/stock options: Pfizer (Pharmaceuticals) and Gilead (Pharmaceuticals). M.H. – Data Safety Monitoring Board member: Parexel and Advarra. Institutional research funding: Novartis and Vanquish. P.Y.W. – research support: AstraZeneca, Black Diamond, Bristol Meyers Squibb, Celgene, Chimerix, Eli Lily, Erasca, Genentech/Roche, Kazia, MediciNova, Merck, Novartis, Nuvation Bio, Servier, Vascular Biogenics, and VBI Vaccines. Advisory board/consultant: AstraZeneca, Black Diamond, Celularity, Chimerix, Day One Bio, Genenta, Glaxo Smith Kline, Merck, Mundipharma, Novartis, Novocure, Nuvation Bio, Prelude Therapeutics, Sapience, Servier, Sagimet, Vascular Biogenics, and VBI Vaccines. R.C.H. has patents related to the drug terameprocol and is affiliated with Erimos Pharmaceuticals, which holds rights to the drug. S.G. is an independent contractor/consultant to Erimos Pharmaceuticals, LLC with no ownership or other financial interest in Erimos Pharmaceuticals or its products. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: CNS cancer; EM-1421; NDGA; Sp1 transcription factor; astrocytoma (MeSH); brain malignancy; brain tumor; glioblastoma; glioma (MeSH); tetra-o-methyl nordihydroguaiaretic acid |
| سلسلة جزيئية: | ClinicalTrials.gov NCT02575794 |
| تواريخ الأحداث: | Date Created: 20240702 Date Completed: 20240717 Latest Revision: 20240717 |
| رمز التحديث: | 20240718 |
| DOI: | 10.1016/j.xcrm.2024.101630 |
| PMID: | 38955178 |
| قاعدة البيانات: | MEDLINE |
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