Veliparib in Combination With Carboplatin for the Treatment of Triple Negative Breast Cancer

Abstract

The invention relates to a method for the treatment of triple negative breast cancer in a subject, comprising administering to the subject an effective amount of 2-[(2R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide, or a pharmaceutically acceptable salt thereof, and an effective amount of carboplatin, in combination with standard of care.

What is claimed is: 
     
         1 . A method for the treatment of BRCA breast cancer in a subject, comprising administering to the subject in need thereof a first chemotherapy segment comprising administering a therapeutically effective amount of 2-[(2R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide. 
     
     
         2 . The method of  claim 1 , wherein the therapeutically effective amount of 2-[(2R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide is administered twice a day continuously for twelve weeks. 
     
     
         3 . The method of  claim 2 , wherein 40 mg-125 mg of 2-[(2R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide is administered to the subject twice a day continuously for twelve weeks. 
     
     
         4 . The method of  claim 3 , wherein 50 mg of 2-[(2R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide is administered to the subject twice a day continuously for twelve weeks. 
     
     
         5 . The method of  claim 1 , wherein administering to the subject in need thereof a first chemotherapy segment comprising administering
 (a) a therapeutically effective amount of paclitaxel; and   (b) a therapeutically effective amount of carboplatin.   
     
     
         6 . The method of  claim 5 , wherein the therapeutically effective amount of paclitaxel is administered on day 1 of twelve 7-day cycles. 
     
     
         7 . The method of  claim 5 , wherein the therapeutically effective amount of carboplatin is administered on day 1 of four 21-day cycles. 
     
     
         8 . The method of  claim 6 , wherein 80 mg/m 2  paclitaxel is administered on day 1 of twelve 7-day cycles. 
     
     
         9 . The method of  claim 7 , wherein area under the curve (AUC) 6 mg/mL/min carboplatin is administered on day 1 of four 21-day cycles. 
     
     
         10 . The method of  claim 1 , wherein the first chemotherapy segment is followed by a second chemotherapy segment comprising administering to the subject
 (a) 60 mg/m 2  doxorubicin on day 1 of four 14-day cycles; and   (b) 600 mg/m 2  cyclophosphamide on day 1 of four 14-day cycles.   
     
     
         11 . The method of  claim 1 , wherein the first chemotherapy segment is followed by a second chemotherapy segment comprising administering to the subject
 (a) 60 mg/m 2  doxorubicin on day 1 of four 21-day cycles; and   (b) 600 mg/m 2  cyclophosphamide on day 1 of four 21-day cycles.   
     
     
         12 . The method of  claim 1 , wherein the subject has early-stage breast cancer. 
     
     
         13 . The method of  claim 1 , wherein the subject is a candidate for surgery. 
     
     
         14 . The method of  claim 13 , wherein the subject has surgery approximately 4-8 weeks after the last chemotherapy treatment. 
     
     
         15 . The method of  claim 14 , wherein the subject has a mastectomy. 
     
     
         16 . The method of  claim 14 , wherein the subject has breast conservation surgery. 
     
     
         17 . The method of  claim 1 , wherein the BRCA breast cancer has a BRCA1 mutation. 
     
     
         18 . The method of  claim 1 , wherein the BRCA breast cancer has a BRCA2 mutation. 
     
     
         19 . A method for the treatment of BRCA breast cancer in a subject, comprising administering to the subject in need thereof a first chemotherapy segment comprising administering
 (c) 40 mg-125 mg of 2-[(2R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide twice a day continuously for twelve weeks;   (d) 80 mg/m 2  paclitaxel on day 1 of twelve 7-day cycles; and   (e) area under the curve (AUC) 6 mg/mL/min carboplatin on day 1 of four 21-day cycles.   
     
     
         20 . The method of  claim 19 , wherein 50 mg of 2-[(2R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide is administered to the subject twice a day continuously for twelve weeks. 
     
     
         21 . The method of  claim 19 , wherein the first chemotherapy segment is followed by a second chemotherapy segment comprising administering to the subject
 (c) 60 mg/m 2  doxorubicin on day 1 of four 14-day cycles; and   (d) 600 mg/m 2  cyclophosphamide on day 1 of four 14-day cycles.   
     
     
         22 . The method of  claim 19 , wherein the first chemotherapy segment is followed by a second chemotherapy segment comprising administering to the subject
 (c) 60 mg/m 2  doxorubicin on day 1 of four 21-day cycles; and   (d) 600 mg/m 2  cyclophosphamide on day 1 of four 21-day cycles.   
     
     
         23 . The method of  claim 19 , wherein the subject has early-stage breast cancer. 
     
     
         24 . The method of  claim 19 , wherein the subject is a candidate for surgery. 
     
     
         25 . The method of  claim 24 , wherein the subject has surgery approximately 4-8 weeks after the last chemotherapy treatment. 
     
     
         26 . The method of  claim 25 , wherein the subject has a mastectomy. 
     
     
         27 . The method of  claim 25 , wherein the subject has breast conservation surgery. 
     
     
         28 . The method of  claim 19 , wherein the BRCA breast cancer has a BRCA1 mutation. 
     
     
         29 . The method of  claim 19 , wherein the BRCA breast cancer has a BRCA2 mutation. 
     
     
         30 . A method for the treatment of BRCA breast cancer in a subject, comprising:
 administering to the subject in need thereof a first chemotherapy segment and a second chemotherapy segment, the first chemotherapy segment consisting of a therapeutically effective amount of 2-[(2R)-2 methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide and carboplatin, and the second chemotherapy segment comprising standard chemotherapy comprising doxorubicin, cyclophosphamide, paclitaxel, or combinations thereof.