| General information |
| Database: | DB00249 |
| Objective: | The PTEN tumor suppressor is frequently lost in CRPC, with activation of AktmTOR signaling, driving growth. They conducted a phase I trial of the mTOR inhibitor, everolimus, and docetaxel in CRPC. |
| Authors: | Courtney KD, et al |
| Title: | a phase I study of everolimus and docetaxel in patients with castrationresistant prostate cancer. |
| Journal: | Clin Genitourin Cancer. |
| Year: | 2015 |
| PMID: | 25450031 |
| Trial Design |
| Clinical Trial Id: | NCT00459186 |
| Agent: | everolimus
|
| Target: | Serine/threonineprotein kinase mTOR
|
| Cancer Type: | prostate cancer |
| Cancer Subtype: | castrationresistant prostate cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | everolimus+ docetaxel |
| Study Type: | a phase I study |
| Key Patients Feature: | Eligible patients had progressive, metastatic, chemotherapynaive CRPC. |
| Biomarker: | PSA |
| Biomark Analysis: | Serum prostatespecific antigen levels were prospectively monitored as a biomarker for cancer activity. |
| Control Group Info: | single arm |
| Treatment Info: | Patients received everolimus 10 mg daily for 2 weeks and underwent a restaging FDGPET/computed tomography scan. Patient cohorts were subsequently treated at 3 dose levels of everolimus with docetaxel: 5 mg to 60 mg/m(2), 10 mg to 60 mg/m(2), and 10 mg to 70 mg/m(2). |
| Primary End Point: | the safety and tolerability of combination therapy. |
| Secondary End Point: | NA |
| Patients Number: | 19 |
| Trial Results |
| DLT_MTD: | Serum concentrations of everolimus when administered with docetaxel were 1.5 to 14.8 ng/mL in patients receiving 5 mg everolimus and 4.5 to 55.4 ng/mL in patients receiving 10 mg everolimus. |
| Objective Response Rate: | Four patients had partial metabolic response (PMR) using FDGPET. Five of 12 evaluable patients experienced a prostatespecific antigen (PSA) reduction more than and equal to 50% during treatment with everolimus together with docetaxel. All 4 patients with a PMR according to PET imaging experienced a PSA reduction in response to everolimus with docetaxel, and 3 of 4 had PSA declines more than and equal to 50%. |
| Disease Control Rate: | 12 had stable metabolic disease, and 2 had progressive metabolic disease after a 2week treatment with everolimus alone |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Common toxicities were hematologic and fatigue. |
| Conclusions: | Everolimus 10 mg daily and docetaxel 60 mg/m(2) was safe in CRPC patients and these they were the recommended doses in combination. FDGPET response might serve as a biomarker for target inhibition by mTOR inhibitors. |