Date: 2016-09-26
Type of information: update on patient enrollment
phase: 2-3
Announcement: update on patient enrollment
Company: Mateon Therapeutics (USA - CA), previously known as Oxigene (USA - CA)
Product: CA4P (fosbretabulin tromethamine)
Action
mechanism: vascular disrupting agent/mitotic inhibitor/tubulin binder. 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.
Disease: platinum-resistant ovarian cancer
Therapeutic area: Cancer - Oncology
Country: United States, Belgium
Trial
details: FOCUS is a multicenter, multinational, randomized, double-blind, 2-arm, parallel-group, Phase 2/3 study to evaluate the efficacy and safety of Physician's Choice Chemotherapy ([PCC] Weekly Paclitaxel or Pegylated Liposomal Doxorubicin [PLD]) 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 September 26, 2016, Mateon Therapeutics announced a collaboration under which sites affiliated with US Oncology Research will participate in the FOCUS Study, Mateon's recently initiated phase 2/3 clinical trial in platinum-resistant ovarian cancer. One of the largest community-based oncology research programs in the U.S. , US Oncology Research has nearly 150 affiliated locations as well as more than 900 affiliated investigators. * On June 23, 2016, Mateon Therapeutics, previously known as Oxigene, announced that it has enrolled the first patient into its FOCUS Study, a phase 2/3 clinical trial of CA4P for the treatment of patients with platinum-resistant ovarian cancer. The FOCUS Study is designed to demonstrate whether the addition of CA4P to bevacizumab and chemotherapy, the current standard of care for platinum-resistant ovarian cancer, improves treatment outcomes for these patients.
The FOCUS Study has two stages. In the first stage the company plans to enroll up to 80 patients and conduct regular interim analyses to verify the safety and efficacy of the drug combination and to confirm powering assumptions for the second stage. In the second stage, which would support a New Drug Application (NDA) if positive, the company plans to enroll up to 356 patients without any planned interim analyses. The primary endpoint of the FOCUS Study is progression free survival (PFS). The company will also evaluate CA4P's effect on objective response rate (ORR), overall survival (OS) and other parameters.
