| General information |
| Database: | DB00226 |
| Objective: | To determine the clinical activity of OGX011, an antisense inhibitor of clusterin, in combination with docetaxel/prednisone in patients with metastatic castrationresistant prostate cancer. |
| Authors: | Chi KN, et al |
| Title: | Randomizedphase II study of docetaxel and prednisone with or without OGX011 in patients with metastatic castrationresistant prostate cancer. |
| Journal: | J Clin Oncol. |
| Year: | 2010 |
| PMID: | 20733135 |
| Trial Design |
| Clinical Trial Id: | NCT00258388 |
| Agent: | custirsen
|
| Target: | Clusterin (CLU)
|
| Cancer Type: | prostate cancer |
| Cancer Subtype: | advanced castrationresistant prostate cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | docetaxel+prednisone+OGX011 |
| Study Type: | a randomizedphase II study |
| Key Patients Feature: | Eligible patients had a pathologic diagnosis of prostate adenocarcinoma with evidence of metastases and progression on androgen ablative therapy defined as the development of new metastatic lesions or increasing PSA. |
| Biomarker: | PSA |
| Biomark Analysis: | NA |
| Control Group Info: | docetaxel and prednisone without OGX011 |
| Treatment Info: | patients were randomly assigned 1:1 to receive docetaxel/prednisone either with (arm A) or without (arm B) OGX011 640 mg intravenously weekly. |
| Primary End Point: | the proportion of patients with a prostatespecific antigen (PSA) decline of more than and equal to 50% from baseline, with the experimental therapy being considered of interest if the proportion of patients with a PSA decline was more than 60%. |
| Secondary End Point: | objective response rate, progression free survival (PFS), overall survival (OS), and changes in serum clusterin. |
| Patients Number: | 82 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | After cycle 1, median serum clusterin decreased by 26% in arm A and increased by 0.9% in arm B (P < .001). PSA declined by more than and equal to 50% in 58% of patients in arm A and 54% in arm B. Partial response occurred in 19% and 25% of patients in arms A and B, respectively. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 7.3 months (95% CI, 5.3 to 8.8 months) vs. 6.1 months (95% CI, 3.7 to 8.6 months) |
| Median OS A vs. C: | 23.8 months (95% CI, 16.2 months to not reached) vs.16.9 months (95% CI, 12.8 to 25.8 months); Baseline factors associated with improved OS on exploratory multivariate analysis were an Eastern Cooperative Oncology Group performance status of 0 (hazard ratio [HR], 0.27; 95% CI, 0.14 to 0.51), presence of bone or lymph node metastases only (HR, 0.45; 95% CI, 0.25 to 0.79), and treatment assignment to OGX011 (HR, 0.50; 95% CI, 0.29 to 0.87). |
| Adverse Event(agent arm): | OGX011 adverse effects included rigors and fevers. |
| Conclusions: | Treatment with OGX011 and docetaxel was well tolerated with evidence of biologic effect and was associated with improved survival. Further evaluation is warranted. |