A multicenter, phase 1, Adult Brain Tumor Consortium trial of oral terameprocol for patients with recurrent high-grade glioma (GATOR) Journal Article
| Authors: | Ahluwalia, M. S.; Peereboom, D. M.; Ozair, A.; Khosla, A. A.; Ozair, A.; Rudek, M.; Ye, X.; Holdhoff, M.; Grossman, S. A.; Ye, X.; Lieberman, F. S.; Piotrowski, A. F.; Nabors, B.; Desai, A.; Lesser, G.; Huang, R. C.; Glenn, S.; Wen, P. Y.; Wen, P. Y. |
| Article Title: | A multicenter, phase 1, Adult Brain Tumor Consortium trial of oral terameprocol for patients with recurrent high-grade glioma (GATOR) |
| Abstract: | 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). © 2024 The Author(s) |
| Keywords: | vasculotropin; adult; clinical article; controlled study; aged; aged, 80 and over; middle aged; clinical trial; drug tolerability; fatigue; bevacizumab; placebo; area under the curve; drug safety; drug approval; temozolomide; nuclear magnetic resonance imaging; brain tumor; glioma; brain neoplasms; cancer grading; endometrium cancer; mass spectrometry; progression free survival; apoptosis; neutrophil count; phase 2 clinical trial; neoplasm recurrence, local; randomized controlled trial; vomiting; deep vein thrombosis; pathology; cancer therapy; hyperglycemia; lymphocytopenia; hypoxia; lung embolism; hospitalization; karnofsky performance status; multicenter study; tumor recurrence; glioblastoma; transcription factor sp1; sp1 transcription factor; muscle weakness; hypoglycemia; oligodendroglioma; seizure; maximum plasma concentration; drug absorption; maximum tolerated dose; phase 1 clinical trial; tumor growth; peptide vaccine; drug therapy; administration, oral; alopecia; radiosensitizing agent; radiation dose distribution; astrocytoma; lipid metabolism; everolimus; brain hemorrhage; severe combined immunodeficiency; drug delivery system; plasma concentration-time curve; antiviral activity; platelet count; oral drug administration; programmed death 1 ligand 1; mini mental state examination; qt interval; acute myeloid leukemia; nordihydroguaiaretic acid; birth control; neoplasm grading; enzalutamide; very elderly; humans; human; male; female; article; interstitial nephritis; cns cancer; baculoviral iap repeat containing protein 5; astrocytoma (mesh); brain malignancy; em-1421; glioma (mesh); ndga; tetra-o-methyl nordihydroguaiaretic acid; terameprocol |
| Journal Title: | Cell Reports Medicine |
| Volume: | 5 |
| Issue: | 7 |
| ISSN: | 2666-3791 |
| Publisher: | Cell Press |
| Date Published: | 2024-07-16 |
| Start Page: | 101630 |
| Language: | English |
| DOI: | 10.1016/j.xcrm.2024.101630 |
| PUBMED: | 38955178 |
| PROVIDER: | scopus |
| PMCID: | PMC11293336 |
| DOI/URL: | |
| Notes: | Source: Scopus |
