| General information |
| Database: | DB00230 |
| Objective: | Given discrepancies between preclinical and clinical observations of mammalian target of rapamycin (mTOR) inhibition in prostate cancer, they sought to determine the pharmacodynamic effects of the mTOR/TORC1 inhibitor rapamycin in men with intermediate to highrisk prostate cancer undergoing radical prostatectomy. |
| Authors: | Armstrong AJ, et al |
| Title: | A pharmacodynamic study of rapamycin in men with intermediate to highrisk localized prostate cancer. |
| Journal: | Clin Cancer Res |
| Year: | 2010 |
| PMID: | 20501622 |
| Trial Design |
| Clinical Trial Id: | NCT00311623 |
| Agent: | sirolimus/rapamycin
|
| Target: | Serine/threonineprotein kinase mTOR
|
| Cancer Type: | prostate cancer |
| Cancer Subtype: | intermediate to highrisk localized prostate cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a twoarm open label multidose multicenter prospective clinical trial |
| Key Patients Feature: | Eligible treated and control men had prostate cancer clinical stages T1c to T3, no metastases, Gleason sum of 7 to 10, multiple positive diagnostic cores, Eastern Cooperative Oncology Group performance status of 0 to 1, and were a candidate for radical prostatectomy. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Rapamycin was given at 3 or 6 mg orally for 14 days before radical prostatectomy in men with multifocal Gleason sum > or =7 prostate cancer; 10 untreated control subjects were included. |
| Primary End Point: | inhibition of phosphorylation of ribosomal S6 in posttreatment radical prostatectomy versus pretreatment biopsy tumor tissue, pharmacodynamic efficacy. |
| Secondary End Point: | NA |
| Patients Number: | 32 |
| Trial Results |
| DLT_MTD: | No doselimiting toxicities were observed at 3 mg; however, two of two men enrolled at 6 mg experienced doselimiting toxicities including thrombocytopenia and fever with grade 3 stomatitis. |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Adverse events observed at 3 mg included stomatitis, rash, ileus, and neutropenia. |
| Conclusions: | At 3 mg daily, rapamycin successfully and safely inhibited prostate cancer S6 phosphorylation and achieved relatively high prostate tissue concentrations. No effect on AKT phosphorylation, tumor proliferation, or apoptosis was observed. |