PURPOSE Clusterin is an antiapoptotic protein activated in response to cellular stress. OGX-011 is a second-generation antisense oligonucleotide that inhibits clusterin expression. The primary objective of this phase II trial was to assess the safety and efficacy of the combination of OGX-011 and docetaxel for metastatic breast cancer. EXPERIMENTAL DESIGN Women with measurable metastatic breast cancer and <or=1 chemotherapy regimen were eligible. Three loading doses of OGX-011 640 mg i.v. followed by weekly OGX-011 and docetaxel 75 mg/m(2) (every 3 weeks) were given. A two-stage design was used with a hypothesis of H(0) <or=35% and H(a) >or=55%. Objective response in >or=6 of the first 14 patients was required for the trial to continue to the second stage. RESULTS Fifteen patients were enrolled. A median of six cycles were delivered (range, 2-10). Five partial responses were confirmed for a 33% response rate (95% confidence interval, 11.8-61.6%) with a further 9 (60%) patients showing stable disease. The median duration of stable disease was 9.3 months. The median time to progression was 8 months (95% confidence interval, 5.62-9.43 months). Toxic effects were similar to those with single agent docetaxel. Although serum clusterin decreased on treatment, there was no relationship observed between the magnitude of decrease and response. CONCLUSION The combination of OGX-011 and docetaxel at 75 mg/m(2) is well tolerated and clinical activity was seen in these patients with metastatic breast cancer, but there was an insufficient number of responses to meet the criteria for proceeding to the second stage of accrual.