Background: Rapid cycling between high and low testosterone (T) (i.e BAT) produces tumor response in mCRPC, and may overcome resistance to newer AR therapies. Here we report a randomized study comparing BAT to E in men with mCRPC progressing on abiraterone (A). Methods: In this phase 2 trial, men received either T cypionate 400mg IM (BAT) once every 28 days or daily oral E 160mg. Primary endpoint was clinical/radiographic PFS; crossover was permitted at progression. Secondary endpoints were OS, PSA progression to primary and crossover therapy, PSA and objective responses (OR), time to PSA progression from randomization through crossover (PFS2), quality of life (QoL), and AEs. Results: 195 men were randomized (94 to BAT, 101 to E). Results are presented in table. Although diametrically opposed therapies, median PFS and PSA response in the intent-to-treat (ITT) population was not significantly different between BAT and E. OR and OS favored BAT. For those who received BAT and then crossed over to E the PSA50 response was 77.8% and time to PSA progression was 10.9 mo compared to 25.3% and 3.8 mo for those receiving E immediately after A. The sequence of treatment had a significant effect on median PSF2 which was 28.2 mo for men receiving BAT→E vs. 19.6 m for E→BAT. For men who crossed over from BAT to E, OS was 37.3 mo vs. 28.6 months for those receiving E without crossover. AEs were primarily grade 1-2 in the BAT arm and included fatigue, generalized pain, and lower extremity edema. BAT improved QoL (fatigue, physical functioning, sexual function) vs. E. Conclusions: BAT could be safely administered to asymptomatic men with mCRPC. BAT produced a comparable PFS to E in A-refractory mCRPC pts. However, PSA50 and OR after crossover, as well as PFS2, were significantly improved in men who received BAT→E versus E→BAT. OS in men receiving BAT→E was 37.3 mo, exceeding historical expectations. These results support the hypothesis that treatment with BAT is safe, has efficacy and can restore sensitivity to antiandrogens. Clinical trial information: NCT02286921.