US-based clinical stage biopharmaceutical firm Arno Therapeutics (ARNI) has started enrolling patients in a Phase I/II trial (NCT02049190) assessing its oral, anti-progestin hormone blocker ‘onapristone’ in men with advanced castration-resistant prostate cancer (CRPC) after failure of abiraterone or enzalutamide.
In previous Phase II clinical trials, onapristone has shown to exhibit anti-tumour activity in patients with breast cancer.
The pre-clinical testing has showed that onapristone had blocked the activation of the progesterone receptor (PR), which is believed to be a mechanism that inhibits the growth of APR-driven breast, endometrial and other tumours.
The company said that tests for the activated form of the progesterone receptor (APR) have the potential to function as a biomarker of anti-progestin activity, as detected by a companion diagnostic under development.
Enrolment of patients in the randomised, open-label Phase I/II trial follows approval of an Investigational Medicinal Product Dossier from the UK Health Authority, Medicines and Healthcare products Regulatory Agency (MHRA), ethics committee authorisation and subsequent site authorisation.
Arno Therapeutics president and chief executive officer Glenn Mattes said globally, prostate cancer is the second most common cancer in men, and the fifth leading cause of death from cancer in men, with an estimated 1.1 million new cases diagnosed and 307,000 deaths during 2012 alone, according to the International Agency for Research on Cancer.
"These numbers are staggering, and our ultimate goal is to evaluate onapristone in the subset of advanced CRPC patients who are more likely to respond to this personalised treatment, for which there is an immense unmet medical need," Mattes said.
"The trial marks Arno’s second Phase I study actively enrolling this year and we are excited by the momentum generated thus far."
The Phase I/II trial, designed to assess the safety and anti-cancer activity of onapristone in the select patient population, is being carried out at the Institute of Cancer Research, London, and the Royal Marsden NHS Foundation Trust in the UK.
A total of 60 patients will be enrolled in the trial, which additional sites are planned for in the UK.
The company has engaged Biotrial, a drug evaluation and pharmacology research company, as its contract research organisation (CRO) for the Phase I/II trial.
The trial will evaluate onapristone in extended-release tablet formulations in up to five dose levels (10mg-50mg BID) in patients with advanced CRPC where PR may be contributing to tumour progression.
Patients in the trial will be evaluated for whether their tumours express APR, which may help identify patients who are more likely to respond to onapristone.
A second group of patients will be included at the recommended Phase II dose to gain additional understanding of the onapristone safety profile and potential anti-cancer activity.
Image: Micrograph of prostate adenocarcinoma, acinar type, the most common type of prostate cancer. Photo: courtesy of Nephron.