US-based biopharmaceutical firm Exelixis has started a Phase II clinical trial of cabozantinib plus abiraterone in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (CRPC).
Primary endpoint for the randomised, open-label Phase II clinical trial is radiographic progression-free survival (PFS).
The trial is designed to compare abiraterone/prednisone against abiraterone/prednisone in combination with one of the three cabozantinib doses: 40mg daily, 20mg daily, or 20mg every other day.
Around 280 chemotherapy-naïve CRPC patients who have bone metastases are expected to be enrolled in the trial, which will be carried out at around 50 sites in North America.
As well as assessing radiographic PFS, the trial will also involve pre-specified outcome measures of safety and tolerability, pharmacokinetics of cabozantinib in combination with abiraterone, overall survival (OS), and bone scan response by computer-aided detection.
Dana-Farber Cancer Institute clinical director of genitourinary oncology and the lead investigator on the Phase II trial Christopher Sweeney said a growing body of data support the potential clinical utility of cabozantinib in treating patients with metastatic CRPC.
"Phase 1 experience from our institution provided important insight into clinical activity when cabozantinib is administered in combination with full dose abiraterone in this patient population, opening the door to potential new treatment options for CRPC patients who have bone metastases but have not yet received chemotherapy," Sweeney said.
"Continued study of cabozantinib in a variety of CRPC indications may help to advance the treatment of the disease."
Exelixis president and chief executive officer Michael Morrissey said: "With its differentiated mechanism targeting MET, RET, and VEGFR2, we believe cabozantinib has the potential to be therapeutically complementary with prostate cancer therapies such as abiraterone and enzalutamide."
The Phase II trial and the planned Phase I trial of cabozantinib in combination with enzalutamide, which is expected to start in the first half of 2014, are expected to support the company's efforts to realise the full clinical and commercial potential of cabozantinib in CRPC.
Cabozantinib inhibits the activity of tyrosine kinases including MET, RET and VEGFR2, which are involved in both normal cellular function and in pathologic processes such as oncogenesis, metastasis, tumour angiogenesis, and maintenance of the tumour microenvironment.
The US FDA has approved Cometriq (cabozantinib) for the treatment of progressive, metastatic medullary thyroid cancer.