Background: Signaling via Src pathway is thought to be a mediator of resistance to androgen targeted therapy in mCRPC. We sought to determine whether adding the Src inhibitor dasatinib (Das) to abiraterone (Abi) would prolong progression free survival (PFS). Methods: Eligible patients had mCRPC which had progressed on androgen targeted therapies but no prior chemotherapy. Abi was prescribed at 1000 mg daily with prednisone 5 mg BID (both arms) and Das 100 mg daily added for Arm B. Primary endpoint was PFS at 24 weeks. Interim analysis planned after 48 subjects randomized but study terminated early due to lack of funding. PFS was evaluated using logrank testing and responses were compared using Fisher’s exact test. Circulating tumor cells (CTC) were evaluated with EPIC platform. Results: 26 men were randomized, 14 to Abi+Das and 12 to Abi. Median age was 67 (56-85), baseline PSA 19.8 (0.84-1387). Only 1 patient had received ketoconazole, none had received enzalutamide. With 30 months median follow-up, median PFS was 15.7 (95% CI:8.2, 31.1+) months for Abi+Das and 9 (95% CI: 4.4, 45.6+) months for Abi (p = 0.30). 86% were progression free at 24 weeks with Abi+Das compared to 75% on Abi. RECIST responses were seen in 5/14 (35%, 95% CI: 17%, 66%) with 2 CR on Abi+Das and 1/12 (8%, 95% CI (0%, 37%) on Abi (p = 0.16). With a specificity of 83%, the probability that the true rate of CR in intervention arm is higher or doubled (ex: 35% vs 17%) is 71%. Grade > 3 toxicities more common on Das arm included hypertension (43% vs 8% Abi), pleural effusion/dyspnea (14% vs 0 Abi), and gastrointestinal (25% vs 8%). CTC were detected at baseline in 8/17 evaluable patients (3/8 Abi, 5/9 Abi+Das), median 2.7 CTC/mL blood (range 0.5-59.7) At week 4, CTC increased in 1/8 (12.5%) on Abi vs 4/9 (44.4%) on Abi+Das but by week 12 CTC increases persisted in 2/8 (25%) on Abi and 1/9 (11%) on Abi+Das. Conclusions: Das did not significantly prolong PFS in combination with Abi although power was limited due to incomplete study cohort. Abi+Das was associated with robust objective responses including RECIST CR. Clinical trial information: NCT01685125