Claims for Patent: RE50642

Summary for Patent: RE50642

Title:	Anti-androgens for the treatment of non-metastatic castrate-resistant prostate cancer
Abstract:	Described herein are methods of treating non-metastatic castrate-resistant prostate cancer with anti-androgens.
Inventor(s):	Isan Chen
Assignee:	Aragon Pharmaceuticals Inc
Application Number:	US17/896,658
Patent Claims:	1. A method of treating a male human with non-metastatic castration-resistant prostate cancer, the method comprising administering an anti-androgen at a dose of about 30 mg per day to about 480 mg per day to a male human in need of such treatment, wherein the anti-androgen is: 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2 fluoro-N-methylbenzamide, 4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide, or 4-[7-[4-cyano-3-(trifluoromethyl)phenyl]-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide; wherein said method further comprises administering a gonadotropin releasing hormone (GnRH) agonist. 2. The method of claim 1, wherein the non-metastatic castration-resistant prostate cancer is a high risk non-metastatic castration-resistant prostate cancer. 3. The method of claim 1, wherein the anti-androgen is 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide. 4. The method of claim 3, wherein 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide is administered daily to the male human. 5. The method of claim 3, wherein 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5, 7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide (ARN-509) is administered orally to the male human at a dose of about 180 mg per day to about 480 mg per day. 6. The method of claim 3, wherein 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide (ARN-509) is administered orally to the male human at a dose of: (a) about 30 mg per day; (b) about 60 mg per day; (c) about 90 mg per day; (d) about 120 mg per day; or (e) about 240 mg per day. 7. The method of claim 3, wherein 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide is administered orally to the male human on a continuous daily dosage schedule. 8. The method of claim 3, wherein the GnRH agonist is leuprolide, buserelin, naferelin, histrelin, goserelin or deslorelin. 9. The method of claim 1, wherein the anti-androgen is 4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide. 10. The method of claim 9, wherein the GnRH agonist is leuprolide, buserelin, naferelin, histrelin, goserelin or deslorelin. 11. The method of claim 1, wherein the anti-androgen is 4-[7-[4-cyano-3-(trifluoromethyl)phenyl]-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide. 12. The method of claim 11, wherein the GnRH agonist is leuprolide, buserelin, naferelin, histrelin, goserelin or deslorelin. 13. The method of claim 1, wherein the anti-androgen is administered orally to the male human. 14. A method of treating a male human with non-metastatic castration-resistant prostate cancer, the method consisting essentially of administering an anti-androgen at a dose of about 30 mg per day to about 480 mg per day to a male human in need of such treatment, wherein the anti-androgen is: 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2 fluoro-N-methylbenzamide, 4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide, or 4-[7-[4-cyano-3-(trifluoromethyl)phenyl]-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide; wherein said method further comprises administering a gonadotropin releasing hormone (GnRH) agonist. 15. The method of claim 14, wherein the anti-androgen is 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide. 16. The method of claim 15, wherein the GnRH agonist is leuprolide, buserelin, naferelin, histrelin, goserelin or deslorelin. 17. The method of claim 15, wherein 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide (ARN-509) is administered orally to the male human at a dose of: (a) about 30 mg per day; (b) about 60 mg per day; (c) about 90 mg per day; (d) about 120 mg per day; or (e) about 240 mg per day. 18. The method of claim 9, wherein the 4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide is administered orally to the male human at a dose of about 160 mg per day. 19. The method of claim 3, wherein 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide is administered orally to the male human at a dose of about 240 mg per day. 20. The method of claim 3, wherein the GnRH agonist is leuprolide. 21. The method of claim 3, wherein the GnRH agonist is buserelin. 22. The method of claim 3, wherein the GnRH agonist is naferelin. 23. The method of claim 3, wherein the GnRH agonist is histrelin. 24. The method of claim 3, wherein the GnRH agonist is goserelin. 25. The method of claim 3, wherein the GnRH agonist is deslorelin. 26. A method of treating non-metastatic castration-resistant prostate cancer in a male human comprising administering a therapeutically effective amount of an anti-androgen to a male human with a non-metastatic castration-resistant prostate cancer; wherein the anti-androgen is 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro [3.4]oct-5-yl]-2-fluoro-N-methylbenzamide; wherein the anti-androgen is administered in an amount of about 180 mg per day or 120 mg per day; and wherein said method further comprises administering a gonadotropin releasing hormone (GnRH) agonist. 27. The method of claim 26, wherein the anti-androgen is administered in an amount of about 180 mg per day. 28. The method of claim 26, wherein the anti-androgen is administered in an amount of about 120 mg per day. 29. The method of claim 26, wherein the male human was previously treated at 240 mg per day and required dose reduction. 30. The method of claim 26, wherein the male human was previously treated at 240 mg per day and required dose interruption. 31. The method of claim 26, wherein the non-metastatic castration-resistant prostate cancer is a high risk non-metastatic castration-resistant prostate cancer. 32. The method of claim 31, wherein the male human with the high risk non-metastatic castration-resistant prostate cancer has a prostate-specific antigen doubling time (PSADT) that is less than or equal to 10 months. 33. The method of claim 28, wherein the male human has experienced 3 consecutive rises of PSA, 1 week apart, resulting in two 50% increases over the nadir, with the last PSA>2 ng/ml. 34. The method of claim 26, wherein the male human is further treated to maintain castrate levels of testosterone of less than 50 ng/dL. 35. The method of claim 26, wherein the anti-androgen is administered daily to the male human. 36. The method of claim 26, wherein the anti-androgen is administered orally to the male human. 37. The method of claim 26, wherein the anti-androgen is administered to the male human orally and on a continuous daily dosing schedule. 38. The method of claim 26, wherein the male human has previously been treated with either orchiectomy or continuous androgen deprivation therapy (ADT). 39. The method of claim 38, wherein the continuous androgen deprivation therapy comprises administration of a gonadotropin-releasing hormone (GnRH) agonist or antagonist. 40. The method of claim 39, wherein the continuous androgen deprivation therapy comprises administration of a gonadotropin-releasing hormone agonist; and wherein the gonadotropin-releasing hormone is leuprolide, buserelin, nafarelin, histrelin, goserelin, or deslorelin. 41. A method of treating non-metastatic castration-resistant prostate cancer in a male human consisting essentially of administering a therapeutically effective amount of an anti-androgen to a male human with a non-metastatic castration-resistant prostate cancer; wherein the anti-androgen is 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide; wherein the anti-androgen is administered in an amount of about 180 mg per day or 120 mg per day; and wherein said method further comprises administering a gonadotropin releasing hormone (GnRH) agonist. 42. The method of claim 41, wherein the anti-androgen is administered in an amount of about 180 mg per day. 43. The method of claim 41, wherein the anti-androgen is administered in an amount of about 120 mg per day. 44. The method of claim 41, wherein the male human was previously treated at 240 mg per day and required dose reduction. 45. The method of claim 41, wherein the non-metastatic castration-resistant prostate cancer is a high risk non-metastatic castration-resistant prostate cancer. 46. The method of claim 45, wherein the male human with the high risk non-metastatic castration-resistant prostate cancer has a prostate-specific antigen doubling time (PSADT) that is less than or equal to 10 months. 47. The method of claim 45, wherein the male human has experienced 3 consecutive rises of PSA, 1 week apart, resulting in two 50% increases over the nadir, with the last PSA>2 ng/mL. 48. The method of claim 41, wherein the male human is further treated to maintain castrate levels of testosterone of less than 50 ng/dL. 49. The method of claim 41, wherein the anti-androgen is administered daily to the male human. 50. The method of claim 41, wherein the anti-androgen is administered orally to the male human. 51. The method of claim 41, wherein the anti-androgen is administered to the male human orally and on a continuous daily dosing schedule. 52. The method of claim 41, wherein the male human has previously been treated with either orchiectomy or continuous androgen deprivation therapy (ADT). 53. The method of claim 52, wherein the continuous androgen deprivation therapy comprises administration of a gonadotropin-releasing hormone (GnRH) agonist or antagonist. 54. The method of claim 53, wherein the continuous androgen deprivation therapy comprises administration of a gonadotropin-releasing hormone agonist; and wherein the gonadotropin-releasing hormone is leuprolide, buserelin, nafarelin, histrelin, goserelin, or deslorelin. 55. A method of treating non-metastatic castration-resistant prostate cancer in a male human comprising administering a therapeutically effective amount of an anti-androgen to a male human with a non-metastatic castration-resistant prostate cancer; wherein the anti-androgen is 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide; wherein the anti-androgen is administered in an amount of about 180 mg per day; and wherein said method further comprises administering a gonadotropin releasing hormone (GnRH) agonist. 56. A method of treating non-metastatic castration-resistant prostate cancer in a male human consisting essentially of administering a therapeutically effective amount of an anti-androgen to a male human with a non-metastatic castration-resistant prostate cancer; wherein the anti-androgen is 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide; wherein the anti-androgen is administered in an amount of about 180 mg per day; and wherein said method further comprises administering a gonadotropin releasing hormone (GnRH) agonist.