Type of information: Treatment of the first patient
Announcement: treatment of the first patient
Company: Mateon Therapeutics (USA - CA)
Product: CA4P and everolimus
Action mechanism: vascular disrupting agent/mitotic inhibitor/tubulin binder/mTor 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. Mateon has received orphan drug designation for CA4P for the treatment of neuroendocrine tumors from both the FDA and from the EMA. Everolimus is a signal transduction inhibitor. Signal transduction inhibitors stop some of the signals within cells that make them grow and divide. Everolimus stops a particular protein called mTOR from working properly. mTOR controls other proteins that trigger cancer cells to grow. So everolimus helps to stop the cancer growing or may slow it down.
Disease: neuroendocrine tumors
Therapeutic area: Cancer - Oncology
Trial details: Study MCC-2016-088 is designed to demonstrate whether the addition of CA4P to everolimus may improve tumor control without additional toxicity. The study is being sponsored, funded, and conducted by the Markey Cancer Center, with Mateon providing the investigational drug. The study is designed as a single center, open label, phase 1 clinical trial for patients with grade 1-3 gastroenteropancreatic neuroendocrine tumors. In the first part of the study, up to 15 patients will be treated with everolimus in combination with two different dosing regimens of CA4P to establish appropriate CA4P dosing levels and evaluate the safety of the drug combination. The second part of the study is designed to enroll 15 additional patients for assessment of additional safety and efficacy data. Patients enrolled in MCC-2016-088 will be treated with CA4P and everolimus for 12 weeks. (NCT03014297)
Latest news: • On April 20, 2017, Mateon Therapeutics announced that the Markey Cancer Center at the University of Kentucky has enrolled the first patient into a new phase 1 study of CA4P in combination with everolimus for the treatment of neuroendocrine tumors. “This is the first trial testing this hypothesis in neuroendocrine tumors – with CA4P disrupting the existing tumor blood supply and everolimus preventing a new tumor blood supply from re-forming. Our findings from this trial should lead to a larger clinical study once we have identified the optimal dose and schedule for the combination of these two agents.” said Lowell B. Anthony, M.D., Professor of Medicine and Chief, Division of Medical Oncology, Markey Cancer Center, University of Kentucky.