| General information |
| Database: | DB00248 |
| Objective: | To evaluate everolimus, an inhibitor of mTOR, in patients with metastatic castrationresistant prostate cancer (mCRPC), and to explore potentially predictive serum biomarkers by proteomics, the significance of PTEN status in tumor tissue, and the impact of everolimus on immune cell subpopulations and function. |
| Authors: | Templeton AJ, et al |
| Title: | Phase 2 trial of singleagent everolimus in chemotherapynaive patients with castrationresistant prostate cancer (SAKK 08/08). |
| Journal: | Eur Urol. |
| Year: | 2013 |
| PMID: | 23582881 |
| Trial Design |
| Clinical Trial Id: | NCT00976755 |
| Agent: | everolimus
|
| Target: | Serine/threonineprotein kinase mTOR
|
| Cancer Type: | prostate cancer |
| Cancer Subtype: | castrationresistant prostate cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a singlearmphase II trial |
| Key Patients Feature: | chemotherapynaive patients with mCRPC and progressive disease |
| Biomarker: | Higher serum levels of carboxypeptidase M and apolipoprotein B were predictive for reaching the primary end point. Deletion of PTEN was associated with longer PFS and response. |
| Biomark Analysis: | Higher serum levels of carboxypeptidase M and apolipoprotein B /Deletion of PTEN |
| Control Group Info: | single arm |
| Treatment Info: | Everolimus was administered continuously at a dose of 10mg daily. |
| Primary End Point: | progression free survival (PFS) at 12 wk defined as the absence of prostatespecific antigen (PSA), radiographic progression, or clinical progression. |
| Secondary End Point: | NA |
| Patients Number: | 37 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Confirmed PSA response more than and equal to 50% was seen in two (5%), and four further patients (11%) had a PSA decline more than and equal to 30%. |
| 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): | Mucositis/stomatitis, fatigue, skin toxicities, diarrhea, and pain were the most common clinical AEs (occurring in >20% of the patients for all grades). Anemia, lymphopenia, and an increase in aspartate aminotransferase and creatinine were the most common laboratory events. |
| Conclusions: | Everolimus activity in unselected patients with mCRPC is moderate, but PTEN deletion could be predictive for response. Several serum glycoproteins were able to predict PFS at 12 wk. Prospective validation of these potential biomarkers is warranted. |