Emerging Molecularly Targeted Therapies in Castration Refractory Prostate Cancer

Table 1

Selected ongoing and recently concluded phase III trials in castration refractory prostate cancer.

Target	Drug	Trial	Phase	Primary endpoint	Clinical trial identifier number (accessed on January 22, 2013)	Outcome
Androgen dependent pathways
CYP17	Orteronel (TAK-700)	Randomized, double-blind, orteronel plus prednisone versus placebo plus prednisone in mCRPC with prior docetaxel therapy	III	OS	NCT01193257	Ongoing
	Orteronel (TAK-700)	Randomized, double-blind, orteronel plus prednisone versus placebo plus prednisone in progressive, chemotherapy naive mCRPC	III	OS	NCT01193244	Ongoing
	Abiraterone	Randomized, double-blind, prednisone and abiraterone or placebo and prednisone in mCRPC after failed docetaxel	III	OS	NCT00638690	Improved OS with abiraterone
	Abiraterone	Randomized, double-blind, prednisone and abiraterone or placebo and prednisone in chemotherapy naive mCRPC	III	PFS	NCT00887198	Improved radiographic PFS with abiraterone
AR	Enzalutamide (MDV 3100)	Randomized, double-blind, MDV3100 versus placebo in chemotherapy naive progressive mCRPC	III	OS, PFS	NCT01212991	Ongoing
	Enzalutamide (MDV 3100)	Randomized, double-blind, MDV3100 versus placebo in mCRPC with prior docetaxel	III	OS	NCT00974311	Improved OS with enzalutamide
Androgen independent pathways
Src kinase	Dasatinib	Randomized, double-blinded, docetaxel, prednisone, and dasatinib versus docetaxel, prednisone, and placebo in mCRPC	III	OS	NCT00744497	No difference in OS
c-MET	Cabozantinib	Randomized, placebo controlled of mitoxantrone and prednisone versus cabozantinib in mCRPC	III	Pain response	NCT01522443	Ongoing
	Cabozantinib	Randomized, placebo controlled prednisone versus cabozantinib in mCRPC with prior docetaxel and abiraterone or MDV3100	III	OS	NCT01605227	Ongoing
Clusterin	Custirsen (OGX-011)	Randomized, open label with cabazitaxel and prednisone with or without custirsen in second line chemotherapy in mCRPC	III	OS	NCT01578655	Ongoing
	Custirsen (OGX-011)	Randomized, docetaxel and prednisone with and without custirsen in chemotherapy naïve mCRPC	III	OS	NCT01188187	Ongoing
	Custirsen (OGX-011)	Randomized, docetaxel retreatment or cabazitaxel and prednisone with and without custirsen in mCRPC	III	Pain response	NCT01083615	Ongoing
VEGF	Bevacizumab (VEGF antibody)	Randomized, double-blinded, docetaxel and prednisone with and without bevacizumab in mCRPC	III	OS	NCT00110214	No difference in OS
	Aflibercept (VEGF trap)	Randomized, double-blind, aflibercept versus placebo in mCRPC with ongoing docetaxel and prednisone	III	OS	NCT00519285	No difference in OS
	Sunitinib (VEGF tyrosine kinase inhibitor)	Randomized, double-blind, sunitinib and prednisone versus prednisone in mCRPC with prior docetaxel	III	OS	NCT00676650	No difference in OS
Immunotherapy	Prostvac-VF	Randomized Prostvac-VF with and without GM-CSF in chemotherapy naive mCRPC	III	OS	NCT01322490	Ongoing
	Ipilimumab	Randomized ipilimumab versus placebo in chemotherapy naive mCRPC	III	OS	NCT01057810	Ongoing
	Ipilimumab	Randomized ipilimumab versus placebo in mCRPC following radiotherapy with prior docetaxel	III	OS	NCT00861614	Ongoing
	Tasquinimod	Randomized tasquinimod versus placebo in chemotherapy naive mCRPC	III	PFS	NCT01234311	Ongoing

CYP17: Cytochrome P450 17 alpha-hydroxylase and C17,20-lyase; mCRPC: metastatic castration refractory prostate cancer; AR: androgen receptor; OS: overall survival; PFS: progression free survival; c-MET: hepatocyte growth factor receptor; VEGF: vascular endothelial growth factor.