| General information |
| Database: | DB00237 |
| 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: | advanced castrationresistant prostate cancer. |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | everolimus+ docetaxel |
| Study Type: | a phase I trial |
| Key Patients Feature: | Eligible patients were more than and equal to 18 years of age, with histologically proven prostatic adenocarcinoma. Patients had radiographic evidence of metastatic disease with subsequent progression of disease (biochemical or radiographic) with castrate levels of testosterone (testosterone < 50 ng/dL) during androgen deprivation therapy. |
| 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 |
| Secondary End Point: | NA |
| Patients Number: | 19 |
| Trial Results |
| DLT_MTD: | Accrual was 4 patients at level 1, 3 patients at level 2, and 8 patients at level 3. Everolimus 10 mg daily and docetaxel 60 mg/m(2) was safe in CRPC patients and these were the recommended doses in combination. |
| Objective Response Rate: | Four patients had partial metabolic response (PMR) using FDGPET, 12 had stable metabolic disease, and 2 had progressive metabolic disease after a 2week treatment with everolimus alone. 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: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most common toxicities were hematologic, fatigue, fever, diarrhea, nausea, back pain, and bone pain. The most frequent Grade 3 or 4 toxicities were hematologic and febrile neutropenia |
| 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. |