1. In a phase I trial, ODM-201 was well tolerated up to 1800mg per day in prostate cancer patients, without reaching the maximum tolerated dose.
2. In a phase II trial, up to 33% of patients randomized to ODM-201 had a 50% or greater decrease in serum PSA at 12 weeks.
Evidence Rating: 2 (Good)
Study Rundown: Androgen receptor (AR) antagonists, such as enzalutamide, have been shown in randomized controlled trials to increase survival in castration-resistant, metastatic prostate cancer. ODM-201 is a rationally designed pharmaceutical with a novel structure that has a higher binding affinity to the AR. In the phase I study reported in this article, patients were sequentially assigned to open-label doses of ODM-201 escalating from 200 to 1800mg per day. The most common adverse events were fatigue and asthenia. Only one patient developed Grade 3 toxicity. In the phase II portion of the article, patients were randomized to 200, 400, and 1400mg daily of ODM-201. After 12 weeks, 29%, 33%, and 33% of patients in the 200, 400, and 1400mg groups had PSA decrease of 50% or greater compared to onset of treatment. These trials are intrinsically limited by the small sample sizes and lack of a control arm (e.g. standard of care) for comparison. It has however, met criteria to move onto a full, phase III trial.
In Depth [Phase I/II Clinical Trial]: In the phase I trial, 4 patients were assigned to the 200mg group, 7 to the 400mg, 3 to the 600mg, 4 to the 1000mg, 3 to the 1400mg, and 3 to the 1800 mg group. The median time on ODM-201 treatment was 24.8 months. 116 of 125 reported adverse events were grade 1-2. The most common being fatigue and asthenia in 42% of patients, diarrhea in 29%, arthralgia in 25%, back pain in 25%, and headache in 21% of patients. There was one grade 3 case of fatigue reported. The maximum tolerated dose, defined as a grade 4 or higher adverse event, was not observed. In the phase II trial, 38 patients were randomly assigned to 200mg ODM-201, 37 to 400mg, and 35 to 1400mg. The median time on treatment was 11.0 months. After 12 weeks of follow-up, 29% of patients in the 200mg group, 33% in the 400mg group, and 33% in the 1400mg group had a PSA response, defined as above. The greatest absolute proportion of response was in patients who were chemotherapy and CYP17 inhibitor naïve. For the phase II trial, the authors pre-determined that a sample size of 8 assessable patients per dose would confer 80% confidence to reject a PSA response rate of 55% or less at a 1-sided significance level of 0.2, assuming the true response rate to be 70%.
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