REPLATINUM Phase III randomized study: RRx-001 + platinum doublet versus platinum doublet in third-line small cell lung cancer. 
RRx-001 is a cysteine-directed anticancer alkylating agent with activity in a Phase II study in platinum refractory small cell lung cancer.  Here, we describe the design of REPLATINUM, an open-label, Phase III trial.  120 patients with previously platinum-treated small cell lung cancer in third line will be randomized 1:1 to receive RRx-001 followed by four cycles of a platinum doublet, and then alternating cycles of RRx-001 and single agent platinum until progression versus four cycles of a platinum doublet.  At radiologic progression on the platinum doublet, patients may cross over to the RRx-001 arm.  Primary objective: to demonstrate superior progression-free survival in the RRx-001 population.  Secondary objectives: to demonstrate superiority for overall survival and objective response rate.  Clinical Trial registration: NCT03699956.