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 ER-negative, PR-negative, and HER-2 negative cancer of the breast 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 the first chemotherapy segment additionally comprises
 (a) a therapeutically effective amount of carboplatin.   
     
     
         6 . The method of  claim 5 , wherein the subject is undergoing standard chemotherapy. 
     
     
         7 . The method of  claim 6 , wherein the first chemotherapy segment is concurrently administered with standard chemotherapy. 
     
     
         8 . The method of  claim 7 , wherein the standard chemotherapy is a therapeutically effective amount of paclitaxel. 
     
     
         9 . The method of  claim 8 , wherein the therapeutically effective amount of paclitaxel is administered on day 1 of twelve 7-day cycles. 
     
     
         10 . The method of  claim 9 , wherein 80 mg/m 2  paclitaxel is administered on day 1 of twelve 7-day cycles. 
     
     
         11 . The method of  claim 5 , wherein the therapeutically effective amount of carboplatin is administered on day 1 of four 21-day cycles. 
     
     
         12 . The method of  claim 5 , wherein area under the curve (AUC) 6 mg/mL/min carboplatin is administered on day 1 of four 21-day cycles. 
     
     
         13 . The method of  claim 5 , wherein area under the curve (AUC) 6 mg/mL/min carboplatin is administered on day 1 of four 21-day cycles. 
     
     
         14 . The method of  claim 6 , 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 600 mg/m 2  cyclophosphamide on day 1 of four 21-day cycles.   
     
     
         15 . The method of  claim 1 , wherein the subject has early-stage breast cancer. 
     
     
         16 . The method of  claim 1 , wherein the subject is a candidate for surgery. 
     
     
         17 . The method of  claim 16 , wherein the subject has surgery approximately 4-8 weeks after the last chemotherapy treatment. 
     
     
         18 . The method of  claim 17 , wherein the subject has a mastectomy. 
     
     
         19 . The method of  claim 18 , wherein the subject has breast conservation surgery. 
     
     
         20 . A method for the treatment of ER-negative, PR-negative, and HER-2 negative cancer of the breast in a subject undergoing standard chemotherapy, comprising administering to the subject a first chemotherapy segment, wherein the first segment comprises administering
 (a) 40 mg-125 mg of 2-[(2R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide twice a day continuously for twelve weeks; and   (b) area under the curve (AUC) 6 mg/mL/min carboplatin on day 1 of four 21-day cycles.   
     
     
         21 . The method of  claim 20 , wherein the standard chemotherapy is concurrent with the first chemotherapy segment. 
     
     
         22 . The method of  claim 20 , wherein the standard chemotherapy is paclitaxel treatment. 
     
     
         23 . The method of  claim 22 , wherein the standard chemotherapy is 80 mg/m 2  paclitaxel treatment on day 1 of twelve 7-day cycles 
     
     
         24 . The method of  claim 20 , 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. 
     
     
         25 . The method of  claim 20 , 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.   
     
     
         26 . The method of  claim 20 , 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.   
     
     
         27 . The method of  claim 20 , wherein the subject has early-stage breast cancer. 
     
     
         28 . The method of  claim 20 , wherein the subject is a candidate for surgery. 
     
     
         29 . The method of  claim 28 , wherein the subject has surgery approximately 4-8 weeks after the last chemotherapy treatment. 
     
     
         30 . The method of  claim 29 , wherein the subject has a mastectomy. 
     
     
         31 . The method of  claim 30 , wherein the subject has breast conservation surgery.