| General information |
| Database: | DB00243 |
| Objective: | ODM201 is a novel androgen receptor (AR) inhibitor designed to block the growth of prostate cancer cells through highaffinity binding to the AR and inhibition of AR nuclear translocation. This trial assessed ODM201's safety, pharmacokinetics, and activity in men with metastatic castrationresistant prostate cancer. |
| Authors: | Fizazi K, et al |
| Title: | Activity and safety of ODM201 in patients with progressive metastatic castrationresistant prostate cancer (ARADES): an openlabelphase 1 doseescalation and randomisedphase 2 dose expansion trial. |
| Journal: | Lancet Oncol |
| Year: | 2014 |
| PMID: | 24974051 |
| Trial Design |
| Clinical Trial Id: | NCT01317641, and NCT01429064(followup after 12 wweeks) |
| Agent: | ODM201
|
| Target: | androgen receptor (AR)
|
| Cancer Type: | prostate cancer |
| Cancer Subtype: | advanced castrationresistant prostate cancer. |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | an openlabelphase I doseescalation and randomisedphase II dose expansion trial |
| Key Patients Feature: | Men in 23 hospitals across Europe and USA with progressive metastatic castrationresistant prostate cancer, who had castrate concentrations of testosterone and an Eastern Cooperative Oncology Group score of 01 were enrolled. |
| Biomarker: | serum PSA |
| Biomark Analysis: | Serum prostatespecific antigen levels were prospectively monitored as a biomarker for cancer activity. |
| Control Group Info: | single arm |
| Treatment Info: | In the phase 1 part of the trial, patients were given oral ODM201 at a starting daily dose of 200 mg, which was increased to 400 mg, 600 mg, 1000 mg, 1400 mg, and 1800 mg. Inphase 2, patients were randomly assigned centrally and stratified by previous chemotherapy and treatment with CPY17 inhibitors, to receive one of three daily doses of ODM201 (200 mg, 400 mg, and 1400 mg). |
| Primary End Point: | safety and tolerability, the proportion of patients with a PSA response (50% or greater decrease in serum PSA) at week 12 |
| Secondary End Point: | NA |
| Patients Number: | 136 |
| Trial Results |
| DLT_MTD: | No doselimiting toxic effects were reported and the maximum tolerated dose was not reached(phase 1).None of the grade 34 adverse events were deemed to be related to ODM201.phase 2: no patients had a treatmentemergent grade 4 adverse event. |
| Objective Response Rate: | 38 patients who received 200 mg, 39 who received 400 mg, and 33 who received 1400 mg were assessable for PSA response at 12 weeks. 11 (29%) patients in the 200 mg group, 13 (33%) in the 400 mg group, and 11 (33%) in the 1400 mg group had a PSA response at 12 weeks. |
| Disease Control Rate: | view in table |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | three patients reported eight adverse events of grade 3 (fracture, muscle injury, laceration, paralytic ileus, pain, presyncope, urinary retention, and vomiting) and one patient had a grade 4 adverse event (lymphoedema)(phase 1).phase 2:the most common treatmentemergent adverse events were fatigue or asthenia (15 [12%] of 124 patients), hot flush (six [5%]), and decreased appetite (five [4%]). One patient (<1%) had a grade 3 treatmentemergent adverse event (fatigue); |
| Conclusions: | Our results suggest that ODM201 monotherapy in men with progressive metastatic castrationresistant prostate cancer provides disease suppression and that ODM201 has a favourable safety profile. These findings support further investigation of clinical responses with ODM201 in men with castrationresistant prostate cancer. |