Date: 2015-11-21
Type of information: Initiation of the trial
phase: 2-3
Announcement: initiation of the trial
Company: Mateon Therapeutics (USA - CA)
Product: CA4P (fosbretabulin tromethamine) and bevacizumab
Action
mechanism: vascular disrupting agent/mitotic inhibitor/tubulin binder/monoclonal antibody. CA4P (combretastatin-A4 phosphate or fosbretabulin) is an investigational vascular disrupting agent (VDA) product candidate, Upon administration, fosbretabulin is dephosphorylated to its active metabolite, combretastatin A4, which targets and binds to tubulin dimers and prevents microtubule polymerization, thereby resulting in mitotic arrest and apoptosis in endothelial cells. It also disrupts the engagement of the endothelial cell–specific junctional molecule vascular endothelial-cadherin (VE-cadherin) and so the activity of the VE-cadherin/?-catenin/Akt signaling pathway, which may result in the inhibition of endothelial cell migration and capillary tube formation. As a result of fosbretabulin's dual mechanism of action, the tumor vasculature collapses, resulting in reduced tumor blood flow and ischemic necrosis of tumor tissue. Bevacizumab is a humanized antibody to vascular endothelial growth factor (VEGF). It binds VEGF and prevents the interaction of VEGF to its receptors on the surface of endothelial cells. The interaction of VEGF with its receptors leads to endothelial cell proliferation and new blood vessel formation.
Disease: ovarian cancer
Therapeutic area: Cancer - Oncology
Country: Belgium, USA
Trial
details: The study is a multicenter, multinational, randomized, double-blind, 2-arm, parallel-group, Phase 2/3 study to evaluate the efficacy and safety of PCC plus bevacizumab and CA4P versus PCC plus bevacizumab and placebo in subjects with platinum-resistant ovarian cancers (prOC). Subjects with platinum-resistant, recurrent, epithelial ovarian, primary peritoneal or fallopian tube cancer will be randomized 1:1 to receive PCC plus bevacizumab and CA4P or PCC plus bevacizumab and placebo. Subjects will be stratified by selected chemotherapy (PLD vs. paclitaxel), platinum free interval (< 3 vs. 3 to 6 months from last platinum therapy to subsequent progression), and line of therapy (2nd vs. 3rd). This is a 2-part study, consisting of a Phase 2, exploratory study (Part 1) followed by a Phase 3, pivotal study (Part 2). Both parts of the study will have similar overall design. Approximately 80 subjects will be randomized into Part 1 and approximately 356 subjects will be randomized into Part 2. (NCT02641639)
Latest
news: * On December 21, 2015, a Phase 2-3 trial sponsored by Mateon Therapeutics was published on the NIH website ClinicalTrials.gov for CA4P (fosbretabulin tromethamine) and bevacizumab and is currently recruiting participants.
