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

In 2010, an estimated 217,730 new cases of prostate cancer occurred with 32,050 deaths in the United States of America. Prostate cancer exhibits a unique natural history that is a function of therapies rendered. Initially, the disease is treated with androgen deprivation therapy (ADT) with substantial regression of disease in the vast majority of patients. However, the response is short-lived, on the order of 18-24 months, with subsequent resumption of cancer growth manifesting as an increasing PSA, radiographic disease progression, and progressive symptoms related to the increasing disease burden, so called metastatic castration-resistant prostate cancer (CRPC). Almost all prostate cancer deaths occur in men with metastatic castration-resistant disease (CRPC). An appropriate therapeutic strategy would be to utilize agents in combination with ADT that could serve to extend the sensitivity of the disease to primary ADT. The hormonal sensitive state, when the tumor burden is dramatically lowered due to therapeutic response, could represent the optimal context to introduce novel agents, leading to cytoreduction and/or maintenance of the hormone-sensitive state. It has been demonstrated that the proangiogenic factor FGF-2 appears to play a central role in angiogenesis in hormone sensitive prostate cancer (HSPC). Thus targeting FGF-2 in conjunction with primary ADT may represent a novel therapeutic strategy in the initial treatment of metastatic HSPC. Dovitinib is a broad-targeted-profiled RTK inhibitor active against VEGF, FGF and PDGF. Anti-tumor effects for this agent may, therefore, be secondary to anti-angiogenesis, anti-proliferative activity against tumor cells, and anti-stromal activity. The study will enroll patients with metastatic prostate disease receiving initial ADT. Participants will be randomized to receive ADT alone, or in combination with Dovitinib. Participants will be stratified based on ECOG PS, Prior ADT \> or \< 30 days, and disease location (bone only vs. other). ADT will be administered per standard of care on both treatment arms. Patients randomized to the combination arm will receive ADT plus Dovitinib at a dose of 500 mg/day given on a five-days-on-two-days-off schedule. One cycle equals 28 days. Dovitinib cycles will repeat continuously until disease progression, or removal from study for other reasons. Patients must begin Dovitinib within 120 days after the start of ADT. Thereafter, patients will be allowed to remain on the study until unacceptable side effect(s) occur, or until there is disease progression to castration-resistance status. Quality of life will be assessed during the course of the study utilizing the Functional Assessment of Cancer Therapy-Prostate (self administered FACT-P). Blood samples obtained at specified time points will be collected for research purposes from participants who provide consent to do so. Biomarkers pertinent to the hypothesized mechanism of action will be evaluated. Circulating tumor cells (CTC) will be enumerated at baseline (CellSearch™), and every 3 months thereafter. An additional citrate tube of blood will be collected for CTC-based ex-vivo culture analysis with each CTC draw. Samples of archival prostate biopsy specimens will also be analyzed for specific proteins related to Dovitinib's mechanism of action.