Date: 2016-07-21
Type of information: Recruitment of the first patient
phase: 1b-2
Announcement: recruitment of the first patient
Company: Mateon Therapeutics (USA - CA), Novartis (Switzerland)
Product: CA4P (fosbretabulin tromethamine) and pazopanib
Action
mechanism: vascular disrupting agent/mitotic inhibitor/tubulin binder/angiogenesis inhibitor/ tyrosine kinase inhibitor.. 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. Pazopanib is a multi-targeted receptor tyrosine kinase inhibitor. Its chemical name is 5-[[4-[(2,3-dimethyl-2H-indazol-6yl)methylamino]-2-pyrimidinyl]amino]-2-methylbenzenesulfonamide monohydrochloride.
Disease: ovarian cancer
Therapeutic area: Cancer - Oncology
Country: UK
Trial
details: The PAZOFOS Study is a Phase 1b/2 clinical trial in patients with recurrent ovarian cancer that will assess the efficacy and safety of the combination of Mateon's investigational drug CA4P plus Novartis' approved tyrosine kinase inhibitor pazopanib (Votrient®) compared to pazopanib alone. The first part of the Pazofos study is to find the recommended dosages of a combination of two drugs: pazopanib and fosbretabulin, which will be given to female patients with relapsed ovarian cancer. The second part of the study involves comparing the recommended dose of pazopanib and fosbretabulin in combination against pazopanib alone in female patients with relapsed ovarian cancer to determine whether the combination is more beneficial that pazopanib on it's own. (NCT02055690)
Latest
news: * On July 21, 2016, Mateon Therapeutics announced that the first patient has been enrolled into the Phase 2 portion of the PAZOFOS Study. The primary outcome measure of the Phase 2 portion of the study is progression free survival measured by RECIST; secondary endpoints include safety, overall survival, objective response rate and relevant biomarkers. The study is designed to enroll 128 patients at ten sites in the United Kingdom . PAZOFOS is sponsored by The Christie NHS Foundation Trust and coordinated by the Manchester Academic Health Science Centre , Trials Coordination Unit (MAHSC-CTU) with additional support from The University of Manchester , the Royal Marsden NHS Foundation Trust and Mount Vernon Cancer Centre (portion of the East and North Hertfordshire NHS Trust ). CA4P and pazopanib are being provided by Mateon and Novartis, respectively. * On February 2, 2014, a Phase 1b-2 trial was published on the NIH website ClinicalTrials.gov for pazopanib +/- fosbretabulin and is currently recruiting participants.
