A method of treating a subject hosting a non-ACTH-secreting pancreatic tumor, the method comprising administering to the subject an effective amount of an antimicrotubule agent selected from a vinca alkaloid and a taxane, and administering between about 20 milligrams per day (mg/day) and about 1000 mg/day of a nonsteroidal selective glucocorticoid receptor modulator (SGRM), wherein the SGRM comprises a fused azadecalin structure 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,
- and salts thereof;
- or
- a heteroaryl-ketone fused azadecalin structure 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, CN, N-oxide, C3-8 cycloalkyl, and C3-8 heterocycloalkyl;
- ring J is selected from the group consisting of a cycloalkyl ring, a heterocycloalkyl ring, an aryl ring and a heteroaryl ring, wherein the heterocycloalkyl and heteroaryl rings have 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, wherein the heterocycloalkyl groups are optionally substituted with 1-4 R2c groups;
- alternatively, two R2 groups linked to the same carbon are combined to form an oxo group (═O);
- alternatively, two R2 groups 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 R2d groups;
- R2a and R2b are each independently selected from the group consisting of hydrogen and C1-6 alkyl;
- each R2c is independently selected from the group consisting of hydrogen, halogen, hydroxy, C1-6 alkoxy, C1-6 haloalkoxy, CN, and NR2aR2b;
- each R2d is independently selected from the group consisting of hydrogen and C1-6 alkyl, or two R2d groups attached to the same ring atom are combined to form (═O);
- R3 is selected from the group consisting of phenyl and pyridyl, each optionally substituted with 1-4 R3a groups;
- each R3a is independently selected from the group consisting of hydrogen, halogen, and C1-6 haloalkyl;
- and
- subscript n is an integer from 0 to 3;
- and salts thereof;
- or
- an octahydro fused azadecalin structure 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 R2c groups;
- R2a, R2b and R2c are each independently selected from the group consisting of hydrogen and C1-6 alkyl;
- each R3a is independently halogen;
- and
- subscript n is an integer from 0 to 3,
- and salts thereof,
- to reduce the tumor load of the pancreatic tumor.