A Study of Dovitinib With Androgen Deprivation Therapy (ADT) in Patients With Metastatic Prostate Cancer Receiving Primary ADT

Summary

This study will evaluate if adding the investigational drug Dovitinib to standard androgen ablation therapy (ADT) is beneficial in prolonging the time to disease progression in patients with metastatic prostate cancer who are receiving ADT for the first time. Dovitinib belongs to the class of drugs known as tyrosine kinase receptor inhibitors. Tyrosine kinase receptor inhibitors have been shown to have anti-tumor effects and inhibit new blood vessel formation. New blood vessel development is necessary for the growth and spread of certain tumors, such as prostate cancer. It is thought that by inhibiting new blood vessel formation, any existing or new tumors may be unable to grow. Dovitinib targets existing cancer cells and also works to stop the formation of new blood vessels. Patients will be randomly assigned to received ADT alone or ADT plus Dovitinib. ADT will be administered per standard of care. Dovitinib will be taken by mouth once daily for 5 continuous days, followed by 2 days with no Dovitinib. This schedule will repeat and continue until disease progression or removal from treatment for other reasons. Participants may start ADT prior to entering the study; however, treatment with Dovitinib must begin no later than 120 days from the start of ADT. Participants will be asked to donate blood samples for research purposes; this is an optional part of the study. Research on blood samples will study circulating tumor cells and certain biomarkers (proteins on cells) to increase the understanding of prostate cancer and explore if certain biomarkers can help predict how tumors will react to treatment. Samples of existing tumor tissue will also be examined for research purposes.

Timeline

Start

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Primary completion

2014-08

Completion

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Publications

• Background Goodman OB Jr, Febbraio M, Simantov R, Zheng R, Shen R, Silverstein RL, Nanus DM. Neprilysin inhibits angiogenesis via proteolysis of fibroblast growth factor-2. J Biol Chem. 2006 Nov 3;281(44):33597-605. doi: 10.1074/jbc.M602490200. Epub 2006 Aug 28.
• Background Horiguchi A, Zheng R, Goodman OB Jr, Shen R, Guan H, Hersh LB, Nanus DM. Lentiviral vector neutral endopeptidase gene transfer suppresses prostate cancer tumor growth. Cancer Gene Ther. 2007 Jun;14(6):583-9. doi: 10.1038/sj.cgt.7701047. Epub 2007 Apr 6.
• Background Horiguchi A, Chen DY, Goodman OB Jr, Zheng R, Shen R, Guan H, Hersh LB, Nanus DM. Neutral endopeptidase inhibits prostate cancer tumorigenesis by reducing FGF-2-mediated angiogenesis. Prostate Cancer Prostatic Dis. 2008;11(1):79-87. doi: 10.1038/sj.pcan.4500984. Epub 2007 Jun 12.
• Background Goodman OB Jr, Symanowski JT, Loudyi A, Fink LM, Ward DC, Vogelzang NJ. Circulating tumor cells as a predictive biomarker in patients with hormone-sensitive prostate cancer. Clin Genitourin Cancer. 2011 Sep;9(1):31-8. doi: 10.1016/j.clgc.2011.04.001. Epub 2011 Jun 25.
• Background Mitra R, Chao OS, Nanus DM, Goodman OB Jr. Negative regulation of NEP expression by hypoxia. Prostate. 2013 May;73(7):706-14. doi: 10.1002/pros.22613. Epub 2012 Nov 8.

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