| General information |
| Database: | DB00245 |
| Objective: | Few options are available after taxanebased therapy in men with CRPC. Genetic alterations involving the mTOR pathway have been associated with CRPC development, raising the hypothesis that blocking mTOR signaling may be an effective targeted approach to treatment. |
| Authors: | Amato RJ, et al |
| Title: | Safety and preliminary efficacy analysis of the mTOR inhibitor ridaforolimus in patients with taxanetreated, castrationresistant prostate cancer. |
| Journal: | Clin Genitourin Cancer |
| Year: | 2012 |
| PMID: | 22695254 |
| Trial Design |
| Clinical Trial Id: | NCT00110188 |
| Agent: | ridaforolimus
|
| Target: | Serine/threonineprotein kinase mTOR
|
| Cancer Type: | prostate cancer |
| Cancer Subtype: | advanced castrationresistant prostate cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | an openlabelphase II study |
| Key Patients Feature: | patients with taxanetreated, castrationresistant prostate cancer. |
| Biomarker: | Serum prostatespecific antigen levels |
| Biomark Analysis: | Serum prostatespecific antigen levels were prospectively monitored as a biomarker for cancer activity. |
| Control Group Info: | single arm |
| 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: | a prostatespecific antigen (PSA) decline of more than and equal to 50% from baseline |
| Secondary End Point: | objective response rate, progression free survival (PFS), overall survival (OS), and changes in serum clusterin. |
| Patients Number: | 38 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | No objective responses were observed |
| Disease Control Rate: | 18 patients (47.4%) had stable disease as their best response. Eight patients (21.1%) had stable disease as their best overall prostatespecific antigen response. |
| Median Time to Progression: | median time to progression with Ridaforolimus was 28 days (95% confidence interval, 2729). |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Ridaforolimus was generally well tolerated, with a safety profile similar to that observed in patients with advanced malignancies. The most common side effects were typically mild or moderate in severity. |
| Conclusions: | Ridaforolimus was generally well tolerated. Treatment did not produce objective responses, but stable disease was observed in some patients with taxanetreated CRPC. Alternative treatment regimens, such as combination therapy with a taxane or in a maintenance treatment paradigm, should be considered for further evaluation in this patient population. |