Methods of Using C-Met Modulators

Abstract

Methods of treating cancer by administering a compound of Formula I, or a pharmaceutically acceptable salt or solvate thereof, in combination with other cancer treatments are described, wherein R 1 is halo; R 2 is halo; and Q is CH or N.

1 . A method of treating cancer, wherein the method comprises administering to a patient in need of the treatment a compound of Formula I: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, in combination with temozolomide (TMZ) or radiation therapy wherein: 
         R 1  is halo; 
         R 2  is halo; and 
         Q is CH or N. 
       
     
     
         2 . A method of treating cancer, wherein the method comprises administering to a patient in need of the treatment a compound of Formula I: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, in combination with radiation therapy (RT) wherein: 
         R 1  is halo; 
         R 2  is halo; and 
         Q is CH or N. 
       
     
     
         3 . The method according to  claim 1 , wherein the compound of Formula I is represented by the following structure: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         4 . The method according to  claim 1 , wherein the compound of Formula I is represented by the following structure: 
       
         
           
           
               
               
           
         
       
     
     
         5 . The method according to  claim 1 , wherein the compound of Formula I, or a pharmaceutically acceptable salt thereof, further comprises a pharmaceutically acceptable carrier, excipient, or diluent. 
     
     
         6 . The method according to according to  claim 1 , further comprising one or more additional treatment(s) selected from (1) surgery, (2) one or more additional chemotherapeutic agent(s), (3) one or more hormone therapy(s), (4) one or more antibody(s), (5) one or more immunotherapy(ies), (6) radioactive iodine therapy, and (7) radiation. 
     
     
         7 . The method according to  claim 1 , wherein the compound of formula I is administered with radiation therapy. 
     
     
         8 . The method according to  claim 1  comprising administering a therapeutically effective dose of compound (I) or a pharmaceutically acceptable salt thereof. 
     
     
         9 . The method according to  claim 1 , comprising administering a therapeutically effective dose of TMZ. 
     
     
         10 . The method according to  claim 2  comprising administering a therapeutically effective dose of radiation. 
     
     
         11 . The method according to  claim 1 , where the cancer is brain cancer. 
     
     
         12 . The method according to  claim 1 , where the cancer is selected from astrocytoma, glioblastoma, giant cell glioblastoma, gliosarcoma, and glioblastoma with oligodendroglial components. 
     
     
         13 . The method according to  claim 1 , wherein the method comprises (1) a concurrent phase, (2) a rest phase and (3) a maintenance phase, wherein:
 the concurrent phase comprises administering radiation and the compound of Formula I to the patient;   the rest phase comprises not administering the compound of Formula I or radiation to the patient; and   the maintenance phase comprises administering the compound of Formula I to the patient.   
     
     
         14 . The method according to  claim 1 , wherein the concurrent phase is 7-8 weeks in duration, and the rest phase is about 4 weeks in duration; and the maintenance phase is of a duration sufficient slow down the cancer growth. 
     
     
         15 . The method according to  claim 1 , wherein the compound of Formula I is administered to the patient in 25-125 mg dosages daily during the concurrent phase; TMZ is administered to the patient in 5-180 mg dosages daily to the patient during the concurrent phase; RT is administered to the patient during the concurrent phase using 1.8-2 Gy/fraction, daily for 5 days/week for a total dose of up to 60 Gy; the compound of Formula I is administered to the patient in 25-125 mg dosages daily during the maintenance phase; and TMZ is administered to the patient in 5-180 mg dosages for 5 consecutive days and repeated every 28 days until the cancer growth is slowed down.