| General information |
| Database: | DB00250 |
| Objective: | Phosphatase and tensin homologue (PTEN) loss is common in advanced prostate cancer, leading to constitutive activation of the PI3 kinase pathway. Temsirolimus blocks mammalian target of rapamycin (mTOR)/target of rapamycin complex 1 (TORC1), a key signaling node in this pathway; its activity in men with advanced castrationresistant metastatic prostate cancer (mCRPC) is unknown. |
| Authors: | Armstrong AJ, et al |
| Title: | a phase II trial of temsirolimus in men with castrationresistant metastatic prostate cancer. |
| Journal: | Clin Genitourin Cancer |
| Year: | 2013 |
| PMID: | 23830964 |
| Trial Design |
| Clinical Trial Id: | NCT00887640 |
| Agent: | temsirolimus
|
| Target: | Serine/threonineprotein kinase mTOR
|
| Cancer Type: | prostate cancer |
| Cancer Subtype: | castrationresistant metastatic prostate cancer. |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase II trial |
| Key Patients Feature: | men with chemorefractory mCRPC who had more than and equal to 5 circulating tumor cells (CTCs) at baseline; Median age was 61 years, with 55% AfricanAmericans and 36% Caucasian patients. Median baseline PSA level was 390 ng/dL, median baseline number of CTCs was 14 cells; 50% of patients had pain, and 63% had undergone more than and equal to 2 previous chemotherapy regimens. |
| Biomarker: | PSA |
| Biomark Analysis: | Serum prostatespecific antigen levels were prospectively monitored as a biomarker for cancer activity. |
| Control Group Info: | single arm |
| Treatment Info: | weekly intravenous temsirolimus administration |
| Primary End Point: | the change in CTCs at 8 weeks |
| Secondary End Point: | progression free survival (PFS) (excluding prostatespecific antigen [PSA]), PSA and radiographic response rates, safety, and survival |
| Patients Number: | 11 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Median CTC decline was 48% and 3 patients experienced decline in CTCs to < 5. however, 73% of men had a persistently unfavorable number of CTCs (more than and equal to 5) and only 1 patient had a more than and equal to 30% PSA decline. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 1.9 months (95% confidence interval [CI], 0.93.1) |
| Median OS A vs. C: | 8.8 months (95% CI, 3.115.6). |
| Adverse Event(agent arm): | Toxicities included grade 4 hypophosphatemia and central nervous system (CNS) hemorrhage, and frequent grade 3 fatigue, anemia, stomatitis, hypokalemia, theyakness, and hyperglycemia. |
| Conclusions: | Temsirolimus lacked sufficient clinical activity in men with mCRPC, despite transient CTC improvements in some men. Future studies should focus on combination approaches or novel PI3K pathway inhibitors. |