Glucocorticoid receptor modulators to treat pancreatic cancer

A method of treating a subject hosting a non-ACTH-secreting pancreatic tumor, the method comprising administering to the subject an effective amount of a chemotherapeutic agent and an effective amount of a nonsteroidal selective glucocorticoid receptor modulator (SGRM) to reduce the tumor load of the pancreatic tumor in the subject, wherein said administering comprises administering a combination therapy comprising administering said chemotherapeutic agent according to an intermittent dosing regimen, and wherein said SGRM is a compound comprising a fused azadecalin structure, said compound having the formula:

• wherein
• L1 and L2 are members independently selected from a bond and unsubstituted alkylene;
• R1 is a member selected from unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted heterocycloalkyl, —OR1A, —NR1CR1D, —C(O)NR1CR1D, and —C(O)OR1A, wherein
• R1A is a member selected from hydrogen, unsubstituted alkyl and unsubstituted heteroalkyl,
• R1C and R1D are members independently selected from unsubstituted alkyl and unsubstituted heteroalkyl,
• wherein R1C and R1D are optionally joined to form an unsubstituted ring with the nitrogen to which they are attached, wherein said ring optionally comprises an additional ring nitrogen;
• R2 has the formula:
• wherein
• R2G is a member selected from hydrogen, halogen, unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, —CN, and —CF3;
• J is phenyl;
• t is an integer from 0 to 5;
• X is —S(O2)—;
• and
• R5 is phenyl optionally substituted with 1-5 R5A groups, wherein
• R5A is a member selected from hydrogen, halogen, —OR5A1, S(O2)NR5A2R5A3, —CN, and unsubstituted alkyl, wherein
• R5A1 is a member selected from hydrogen and unsubstituted alkyl, and
• R5A2 and R5A3 are members independently selected from hydrogen and unsubstituted alkyl,
• or salts and isomers thereof.

A method of treating a subject hosting a non-ACTH-secreting pancreatic tumor, the method comprising administering to the subject an effective amount of a chemotherapeutic agent and an effective amount of a nonsteroidal selective glucocorticoid receptor modulator (SGRM) to reduce the tumor load of the pancreatic tumor in the subject, wherein said administering comprises administering a combination therapy comprising administering said chemotherapeutic agent according to an intermittent dosing regimen, and wherein said SGRM is a compound comprising an octahydro fused azadecalin structure, said compound having the formula:

• wherein
• R1 is a heteroaryl ring having from 5 to 6 ring members and from 1 to 4 heteroatoms each independently selected from the group consisting of N, O and S, optionally substituted with 1-4 groups each independently selected from R1a;
• each R1a is independently selected from the group consisting of hydrogen, C1-6 alkyl, halogen, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, N-oxide, and C3-8 cycloalkyl;
• ring J is selected from the group consisting of an aryl ring and a heteroaryl ring having from 5 to 6 ring members and from 1 to 4 heteroatoms each independently selected from the group consisting of N, O and S;
• each R2 is independently selected from the group consisting of hydrogen, C1-6 alkyl, halogen, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkyl-C1-6 alkoxy, CN, OH, NR2aR2b, C(O)R2a, C(O)OR2a, C(O)NR2aR2b, SR2a, S(O)R2a, S(O)2R2a, C3-8 cycloalkyl, and C3-8 heterocycloalkyl having from 1 to 3 heteroatoms each independently selected from the group consisting of N, O and S;
• alternatively, two R2 groups on adjacent ring atoms are combined to form a heterocycloalkyl ring having from 5 to 6 ring members and from 1 to 3 heteroatoms each independently selected from the group consisting of N, O and S, wherein the heterocycloalkyl ring is optionally substituted with from 1 to 3 R2 groups;
• R2a, R2b and R2c are each independently selected from the group consisting of hydrogen and C1-6 alkyl;
• each R1a is independently halogen;
• and
• subscript n is an integer from 0 to 3,
• or salts and isomers thereof.