Maximum Tolerated Dose and Anti-Tumor Activity of Intraperitoneal Cantrixil (TRX-E-002-1) in Patients with Persistent or Recurrent Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer: Phase I Study Results
Autor: | Daniel J. Berg, Jermaine Coward, Kathleen N. Moore, Paul R. Harnett, James Garner, Ganessan Kichenadasse, Don S. Dizon, Minal A. Barve |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Cancer Research medicine.medical_specialty Ileus medicine.medical_treatment intraperitoneal delivery Stem cell marker Gastroenterology Article 03 medical and health sciences 0302 clinical medicine Internal medicine medicine platinum refractory Adverse effect RC254-282 Chemotherapy business.industry Neoplasms. Tumors. Oncology. Including cancer and carcinogens phase I medicine.disease female genital diseases and pregnancy complications 030104 developmental biology ovarian cancer platinum resistant Oncology Tolerability 030220 oncology & carcinogenesis Fallopian tube cancer Toxicity Ovarian cancer business |
Zdroj: | Cancers, Vol 13, Iss 3196, p 3196 (2021) Cancers Volume 13 Issue 13 |
ISSN: | 2072-6694 |
Popis: | Survival outcomes in ovarian cancer are poor. The aims of this Phase I progressive design study (NCT02903771) were to evaluate the maximum tolerated dose (MTD), tolerability, and antitumor activity of Cantrixil—a novel third-generation benzopyran molecule—in patients (n = 25) with advanced, recurrent/persistent epithelial ovarian, primary peritoneal, or fallopian tube cancer. All had completed ≥ 2 prior regimens 3 (12%) had platinum-refractory disease, and 17 (68%) had platinum-resistant disease. Following intraperitoneal (IP) port placement, patients received weekly IP Cantrixil in 3-week cycles as monotherapy (Cycles 1–2), and then in combination with intravenous (IV) chemotherapy (Cycles 3–8). Part A (dose escalation) enrolled 11 patients in 6 dose-level cohorts. An MTD of 5 mg/kg was established with dose-limiting toxicity of ileus. Most treatment-related adverse events were gastrointestinal. Across Parts A and B (dose expansion), 16 (64%) patients received ≥ 1 3-week Cantrixil cycle, and had ≥ 1 post-baseline efficacy measurement available. The results show promising anti-tumor activity in monotherapy (stable disease rate of 56%) and in combination with IV chemotherapy (objective response rate of 19%, disease control rate of 56%, and median progression-free survival of 13.1 weeks). The molecular target and mechanism of action of Cantrixil are yet to be confirmed. Preliminary analysis of stem cell markers suggests that IP Cantrixil might induce ovarian cancer stem cell death and sensitize cells to standard chemotherapy, warranting further evaluation. |
Databáze: | OpenAIRE |
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