AstraZeneca halts phase III trial of ZIBOTENTAN in non-metastatic castrate resistant prostate cancer

Monday, 7 February 2011

AstraZeneca today announced that the phase III ENTHUSE Study 15, studying zibotentan monotherapy in patients with non-metastatic castrate resistant prostate cancer (CRPC), will be stopped following the results of an early efficacy review by the Independent Data Monitoring Committee (IDMC). The decision was made after this review indicated that zibotentan monotherapy was unlikely to meet its primary efficacy endpoints (progression free survival and overall survival) and therefore unlikely to benefit patients with non-metastatic CRPC.

AstraZeneca felt it was prudent to take an early view on the progress of Study 15 following the announcement in September 2010 that ENTHUSE Study 14, evaluating zibotentan monotherapy, did not show a significant improvement in the primary endpoint of overall survival in patients with metastatic CRPC.

Study 15 is part of the Phase III clinical trial programme, ENTHUSE, which was developed to evaluate the efficacy and safety of zibotentan in extending survival in men with CRPC. The discontinuation of Study 15 concludes the zibotentan monotherapy programme in CRPC. The full data from Study 15 will be published in due course.

ENTHUSE Study 33 is a trial using zibotentan in combination with standard chemotherapy in a more advanced metastatic CRPC setting. This trial will continue and full results are expected in the second half of 2011.


About zibotentan and the Phase III study programme

Zibotentan is a novel once daily tablet and works by blocking the endothelin pathway. As prostate cancer advances, this pathway becomes uncontrolled, which then drives the spread of cancer growth. By blocking the endothelin A receptor in this pathway, zibotentan can slow tumour growth and the spread of cancer cells.

The ENTHUSE (Endothelin A Use) clinical trial programme, consists of thee Phase III clinical studies which were developed to evaluate zibotentan’s efficacy and safety in extending survival in men with CRPC. With the discontinuation of the monotherapy studies 14 and 15, there is one remaining study in the ENTHUSE trial programme.

Study 33 will evaluate zibotentan plus chemotherapy, versus chemotherapy alone, in men whose disease has metastasised and who have been prescribed treatment with chemotherapy Prostate Cancer and CRPC

Prostate cancer primarily affects men over the age of 50. It is the most commonly diagnosed male cancer in many western countries and its incidence is increasing. Worldwide, more than 670,000 men are diagnosed with prostate cancer every year, accounting for one in nine of all new cancers in men. Prostate cancer is the second most common cancer in men after lung cancer and 1 in 5 men with prostate cancer will develop CRPC. CRPC is prostate cancer that is no longer responding to treatments that block the action of testosterone, the naturally occurring hormone that drives cancer growth. Whilst therapies that block testosterone (collectively known as hormonal treatments) provide great benefit for many men, the majority of patients eventually become resistant to hormonal treatments and develop CRPC.

About AstraZeneca

AstraZeneca is a global, innovation-driven biopharmaceutical business with a primary focus on the discovery, development and commercialisation of prescription medicines for gastrointestinal, cardiovascular, neuroscience, respiratory and inflammation, oncology and infectious disease. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information please visit:


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