Erratum to: First-in-human phase I study of SOR-C13, a TRPV6 calcium channel inhibitor, in patients with advanced solid tumors
| Autor: | H. Hirte, T. T. Ilenchuk, Jing Gong, T. Lutes, Siqing Fu, N. Fields, Sarina Anne Piha-Paul, Vivek Subbiah, Li Liu, A. Nemet, C. Rice, J. M. Stewart, Dominique Dugourd, David S. Hong, Stephen Welch |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adult Male TRPV6 Maximum Tolerated Dose Urticaria TRPV Cation Channels Antineoplastic Agents Hypokalemia Pharmacology 03 medical and health sciences Phase I Studies Neoplasms Sor-C13 Humans Pharmacology (medical) In patient Aspartate Aminotransferases RNA Messenger Aged 030102 biochemistry & molecular biology Hypocalcemia Keratin-18 Chemistry Calcium channel Headache Alanine Transaminase First in human Middle Aged Calcium Channel Blockers Phase i study Treatment Outcome Oncology Female Calcium Channels Erratum Peptides |
| Zdroj: | Investigational New Drugs |
| ISSN: | 1573-0646 0167-6997 |
| Popis: | Summary Introduction This was an open-label, dose escalation (3 + 3 design), Phase I study of SOR-C13 in patients with advanced tumors of epithelial origin. Primary objectives were to assess safety/tolerability and pharmacokinetics. Secondary goals were to assess pharmacodynamics and efficacy of SOR-C13. Methods SOR-C13 was administered IV QD on days 1–3 and 8–10 of a 21-day cycle. Doses were 2.75 and 5.5 mg/kg (20-min infusion) and 1.375, 2.75, 4.13 and 6.2 mg/kg (90-min infusion). Toxicity was assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Dose limiting toxicity (DLT) was assessed within the first treatment cycle. Tumors were evaluated, using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, after two cycles. Results Twenty-three patients were treated. No drug-related serious adverse events occurred. DLTs occurred in six patients: asymptomatic, drug-related, transient Grade 2 hypocalcemia (4 patients), and unrelated Grade 3 anemia and Grade 3 atrial fibrillation, 1 patient each. Calcium and vitamin D supplementation eliminated further Grade 2 hypocalcemia. One Grade 3 treatment emergent adverse event, urticaria, was definitely related to SOR-C13. Four possibly drug-related, Grade 3 events (alanine aminotransferase and aspartate aminotransferase elevation, headache, and hypokalemia) were observed. Of 22 evaluable patients, 54.5% showed stable disease ranging from 2.8 to 12.5 months. The best response was a 27% reduction in a pancreatic tumor with a 55% reduction in CA19–9 levels at 6.2 mg/kg. Conclusion SOR-C13 was safe and tolerated up to 6.2 mg/kg. The Maximal Tolerated Dose (MTD) was not established. Stable disease suggested antitumor activity. |
| Databáze: | OpenAIRE |
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