Next Article in Journal
Imaging Mass Spectrometry-Based Proteomic Analysis to Differentiate Melanocytic Nevi and Malignant Melanoma
Previous Article in Journal
Protein Aggregation Patterns Inform about Breast Cancer Response to Antiestrogens and Reveal the RNA Ligase RTCB as Mediator of Acquired Tamoxifen Resistance
 
 
Article

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

1
ICON Cancer Centre, South Brisbane, QLD 4101, Australia
2
School of Medicine, University of Queensland, Brisbane, QLD 4072, Australia
3
Mary Crowley Cancer Research Center, Dallas, TX 75251, USA
4
Flinders Medical Centre, Adelaide, SA 5042, Australia
5
Department of Gynecologic Oncology, University of Oklahoma Health Science Center, Stephenson Cancer Center, Oklahoma City, OK 73104, USA
6
Crown Princess Mary Cancer Centre, Westmead, NSW 2145, Australia
7
Formerly of Kazia Therapeutics Ltd., Sydney, NSW 2000, Australia
8
Kazia Therapeutics Ltd., Sydney, NSW 2000, Australia
9
Lifespan Cancer Institute, Providence, RI 02913, USA
10
The Warren Alpert Medical School, Brown University, Providence, RI 02912, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Charles Theillet
Cancers 2021, 13(13), 3196; https://doi.org/10.3390/cancers13133196
Received: 31 May 2021 / Revised: 24 June 2021 / Accepted: 24 June 2021 / Published: 26 June 2021
(This article belongs to the Section Cancer Therapy)
Survival outcomes with standard cytotoxic chemotherapy are poor, and most patients with ovarian cancer will die with platinum-resistant disease. This may reflect the existence of drug-resistant ovarian cancer stem cells. Cantrixil is a novel third-generation benzopyran molecule, with potent cytotoxicity against chemoresistant ovarian cancer stem cells and chemosensitive ovarian cancer cell lines. The aims of this Phase I study were to define the maximum tolerated dose, tolerability, and antitumor activity of Cantrixil when administered via an intraperitoneal (IP) port. Cantrixil was tolerable even in patients with heavily pretreated disease. This first in-human study has demonstrated the potential for prolonged survival in advanced ovarian cancer by inducing ovarian cancer stem cells’ death and sensitizing cells to standard chemotherapy with IP-administered Cantrixil. Future studies should focus on confirming its mechanism of action alongside further assessment of cancer stem cell biomarkers, and determining optimal clinical settings to maximize survival outcomes in ovarian cancer.
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. View Full-Text
Keywords: ovarian cancer; platinum refractory; platinum resistant; intraperitoneal delivery; phase I ovarian cancer; platinum refractory; platinum resistant; intraperitoneal delivery; phase I
Show Figures

Figure 1

MDPI and ACS Style

Coward, J.I.; Barve, M.A.; Kichenadasse, G.; Moore, K.N.; Harnett, P.R.; Berg, D.; Garner, J.S.; Dizon, D.S. 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. Cancers 2021, 13, 3196. https://doi.org/10.3390/cancers13133196

AMA Style

Coward JI, Barve MA, Kichenadasse G, Moore KN, Harnett PR, Berg D, Garner JS, Dizon DS. 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. Cancers. 2021; 13(13):3196. https://doi.org/10.3390/cancers13133196

Chicago/Turabian Style

Coward, Jermaine I., Minal A. Barve, Ganessan Kichenadasse, Kathleen N. Moore, Paul R. Harnett, Daniel Berg, James S. Garner, and Don S. Dizon. 2021. "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" Cancers 13, no. 13: 3196. https://doi.org/10.3390/cancers13133196

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop