Entry Detail
| General information | |
| Database: | DB00927 |
| Objective: | To determine the efficacy and toxicity of danusertib (formerly PHA739358) administered i.v. over two different dosing schedules with equivalent dose intensity in patients with metastatic castrationresistant prostate cancer with progressive disease after docetaxelbased treatment. |
| Authors: | Meulenbeld HJ, et al |
| Title: | Randomizedphase II study of danusertib in patients with metastatic castrationresistant prostate cancer after docetaxel failure. |
| Journal: | BJU Int. |
| Year: | 2013 |
| PMID: | 22928785 |
| Trial Design | |
| Clinical Trial Id: | NCT00766324 |
| Agent: | danusertib |
| Target: | Aurora kinase A Serine/threonine protein kinase 12 |
| Cancer Type: | prostate cancer |
| Cancer Subtype: | advanced castrationresistant prostate cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | openlabel, multicentrephase II trial |
| Key Patients Feature: | patients with metastatic castrationresistant prostate cancer after docetaxel failure |
| Biomarker: | PSA |
| Biomark Analysis: | NA |
| Control Group Info: | danusertib 330 mg/m(2) over 6 h i.v. on days 1, 8 and 15 versus 500 mg/m(2) over 24 h i.v. on days 1 and 15 (arm B, n = 38), |
| Treatment Info: | patients were randomly assigned (1:1 ratio) to receive either danusertib 330 mg/m(2) over 6 h i.v. on days 1, 8 and 15 (arm A, n = 43) or 500 mg/m(2) over 24 h i.v. on days 1 and 15 (arm B, n = 38), every 4 weeks |
| Primary End Point: | PSA response rate at 3 months. |
| Secondary End Point: | NA |
| Patients Number: | 60 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | 18.6% and 34.2% in arms A and B, respectively. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 12.1 weeks (95% CI 10.9-15.1) for arm A and 12.0 weeks (95% CI 10.3-17.0) for arm B |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most frequent grade more than and equal to 3 drugrelated adverse events were neutropenia in 22 patients (16 arm A; six arm B), fatigue in five patients (four arm A; one arm B) and neutropenic fever (two patients in each arm) (Table 4). Irrespective of the treatment arm, the most common drugrelated adverse events for all grades involved gastrointestinal disorders (61.7%), general disorders and administration site conditions (60.5%) and blood and lymphatic system disorders (50.6%) (Table 4). No drugrelated deaths were reported. One patient died on study due to pneumonia, unlikely to be related to the study drug. |
| Conclusions: | Danusertib monotherapy shows minimal efficacy in patients with castrationresistant prostate cancer. Further studies are required to establish specific biomarkers predictive for either response or prolonged disease stabilization. |