| General information |
| Database: | DB00227 |
| Objective: | Clusterin (CLU) is an antiapoptotic, stressinduced protein conferring treatment resistance when overexpressed. This study tested custirsen, a CLU inhibitor, in patients with metastatic castrationresistant prostate cancer (mCRPC) progressing during or within 6 months of initial docetaxel therapy. |
| Authors: | Saad F, et al |
| Title: | Docetaxel plus oblimersen sodium (Bcl2 antisense oligonucleotide): an EORTC multicenter, randomizedphase II study in patients with castrationresistant prostate cancer. |
| Journal: | Clin Cancer Res. |
| Year: | 2011 |
| PMID: | 21788353 |
| Trial Design |
| Clinical Trial Id: | NA |
| 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: | mitoxantrone + prednisone + custirsen (MPC) |
| Study Type: | a randomizedphase II trial |
| Key Patients Feature: | Patients had a histologic diagnosis of adenocarcinoma of the prostate, metastatic disease by imaging, and 2 or more cycles of firstline docetaxelbased chemotherapy, with disease progression documented within 6 months of discontinuing treatment. |
| Biomarker: | PSA;Low serum CLU levels |
| Biomark Analysis: | Low serum CLU levels during treatment showed superior survival for patients based on modeling with proportional hazard regression with a timedependent covariate and different landmarks. |
| Control Group Info: | docetaxel + prednisone + custirsen (DPC) versus mitoxantrone + prednisone + custirsen (MPC). |
| Treatment Info: | Men were randomized to receive either docetaxel + prednisone + custirsen (DPC) or mitoxantrone + prednisone + custirsen (MPC). |
| Primary End Point: | toxicity, PFS, OS, disease progression, PSA response, TTP and pain response, effect of custirsen on serum clusterin levels |
| Secondary End Point: | NA |
| Patients Number: | 42 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Three of 13 (23%) evaluable patients had objective partial responses.Prostatespecific antigen (PSA) declines of 90% or more, 50% or more, and 30% or more occurred in 4 (20%), 8 (40%), and 11 (55%) patients, respectively.6 of 13 (46%) evaluable patients had pain responses. No objective responses were observed. PSA declines of 50% or more and 30% or more occurred in 6 (27%) and 7 (32%) patients, respectively. |
| Disease Control Rate: | NA |
| Median Time to Progression: | Median time to pain progression (TTPP) was 10.0 months; 10 of 13 (77%) evaluable patients had pain responses. The median TTPP was 5.2 months |
| Median PFS A vs. C: | 7.2 months (95% CI, 4.4-9.3) for DPC and 3.4 months (95% CI, 1.6-5.2) for MPC |
| Median OS A vs. C: | Twenty patients treated with DPC received a median of 8 cycles; overall survival (OS) was 15.8 months. Twentytwo patients treated with MPC received a median of 6 cycles; OS was 11.5 months. |
| Adverse Event(agent arm): | Toxicity was similar in both arms. |
| Conclusions: | Custirsen plus either docetaxel or mitoxantrone was feasible in patients with progressive mCRPC following firstline docetaxel therapy. Pain relief was higher than expected, with interesting correlations bettheyen serum CLU and survival. Aphase III trial evaluating the pain palliation benefit of custirsen with taxane therapy is ongoing. |