Myriad Genetics Inc has initiated the first phase 2 human clinical trial of its therapeutic candidate, Azixa (MPC-6827), in patients with brain cancer.
The phase 2 trial is designed to determine the safety profile of Azixa and the extent of its ability to improve the survival of patients with glioblastoma multiforme, the most common form of primary brain cancer. The trial will compare the survival of patients treated with Azixa to those treated with oxaliplatin, and to those treated with Azixa plus oxaliplatin.
The trial is designed as an adaptive, open label, multiple dose study in patients with recurring or relapsed glioblastoma multiforme. The first stage of the trial is designed to determine the safety and the maximum tolerated dose of Azixa in combination with oxaliplatin, in approximately 16 patients.
The maximum tolerated dose of Azixa alone was determined during the earlier phase 1 trials. The second stage of the trial will then assess the survival of patients treated with the Azixa/oxaliplatin combination therapy compared to Azixa alone or oxaliplatin alone. Patients will be randomised into one of three treatment arms. Periodically, an analysis of efficacy will be conducted to determine the final size of the second stage of the trial.
The lead investigator for the phase 2 Azixa trial in glioblastoma multiforme is Alfred Yung, MD, Professor and Chair, Department of Neuro-Oncology at the MD Anderson Cancer Centre in Houston, TX. The trial is expected to enlist the participation of approximately 50-70 centres in total, through both stages of the phase 2, in the United States and Europe.
"We are pleased to continue the clinical development of this exciting compound," said Adrian Hobden, PhD, president of Myriad Pharmaceuticals Inc. "The ability of Azixa to cross the blood-brain barrier gives us hope that because it can reach the site of the disease, it could be a more effective therapeutic than anything available today."
Azixa has completed two phase 1 clinical trials in patients with refractory solid tumours, one allowing brain metastases and the other requiring known brain metastases. The trials were designed to explore the safety and pharmacokinetics of Azixa and to find the maximum tolerated dose of the compound. The phase 1 studies also found that Azixa demonstrated biological effects on patient tumours that were consistent with the mechanism of the drug.
Azixa has a dual mode of action; it acts as a cytotoxin and a vascular disrupting agent (VDA). VDAs kill tumour cells by reducing the blood supply to a tumour. The disruption of the tumour vasculature results in acute ischemia followed by massive tumour cell death. Azixa is believed to selectively disrupt tumour vasculature and not healthy tissue by inhibiting the formation of microtubules. Tumours rely on microtubules to maintain the cytoskeletal structure of their new vasculature, whereas mature vascular endothelium of healthy tissue uses actin filaments to provide the needed structure.