Treatment of gliomas using organonitro compound combination therapy

Patent metadata

Field	Value
Publication number	US-9987270-B1
Application number	US-201615337378-A
Country	US
Kind code	B1
Filing date	Oct 28, 2016
Priority date	Oct 29, 2015
Publication date	Jun 5, 2018
Grant date	Jun 5, 2018

Abstract

The invention provides therapeutic methods and kits for treating a glioma using a particular dosing regimen of the organonitro compound ABDNAZ, radiation therapy, and one of temozolomide, irinotecan, or bevacizumab.

First claim

The invention claimed is:

1. A method of treating a glioma in a patient, comprising the steps of:
(a) administering to the patient in need thereof a therapeutically effective amount of a formulation comprising temozolomide, and within about 2 days thereafter subjecting the glioma to radiation therapy; and
(b) administering to the patient at least one dose of a therapeutically effective amount of a formulation comprising ABDNAZ within about 7 days of administration of a first dose of the temozolomide; to treat the glioma.

2. The method of claim 1 , wherein the formulation comprising temozolomide is administered daily for at least 6 weeks.

3. The method of claim 2 , wherein the patient receives temozolomide by oral administration at a daily dose of at least 50 mg/m 2 .

4. The method of claim 2 , wherein the patient receives temozolomide by oral administration at a daily dose of about 50 mg/m 2 to about 100 mg/m 2 .

5. The method of claim 2 , wherein the patient receives temozolomide by oral administration at a daily dose of about 75 mg/m 2 .

6. The method of claim 2 , wherein for a duration of at least 6 weeks following administration of the first dose of temozolomide, the patient receives at least one dose each week of a therapeutically effective amount of a formulation comprising ABDNAZ.

7. The method of claim 2 , wherein for a duration of at least 4 weeks following administration of the first dose of temozolomide, the patient receives two doses each week of a therapeutically effective amount of a formulation comprising ABDNAZ.

8. The method of claim 2 , wherein for a duration of at least 6 weeks following administration of the first dose of temozolomide, the patient receives two doses each week of a therapeutically effective amount of a formulation comprising ABDNAZ.

9. The method of claim 8 , wherein any dose of ABDNAZ administered to the patient within 12 hours of administering temozolomide is administered at least 3 hours before administering the temozolomide.

10. The method of claim 8 , wherein each dose of the formulation comprising ABDNAZ is administered to the patient by intravenous infusion providing ABDNAZ in an amount of from about 0.1 mg to about 10 mg.

11. The method of claim 8 , wherein each dose of the formulation comprising ABDNAZ is administered to the patient by intravenous infusion providing ABDNAZ in an amount of from about 0.5 mg to about 4.0 mg.

12. The method of claim 8 , wherein each dose of the formulation comprising ABDNAZ is administered to the patient by intravenous infusion providing ABDNAZ in an amount ranging from about 2 mg/m 2 to about 20 mg/m 2 .

13. The method of claim 8 , wherein the patient receives ABDNAZ within about 3 hours prior to subjecting the glioma to radiation therapy.

14. The method of claim 8 , wherein the patient receives ABDNAZ within about 6 hours prior to subjecting the glioma to radiation therapy.

15. The method of claim 8 , wherein the patient receives ABDNAZ within about 24 hours prior to subjecting the glioma to radiation therapy.

16. The method of claim 8 , wherein the glioma is subjected to radiation therapy once per day for at least 5 days within a 7 day period following administration of the first dose of temozolomide.

17. The method of claim 7 , wherein for a duration of at least 4 weeks following administration of the first dose of temozolomide, the glioma is subjected to radiation therapy once per day for at least 5 days of each week.

18. The method of claim 8 , wherein for a duration of at least 6 weeks following administration of the first dose of temozolomide, the glioma is subjected to radiation therapy once per day for at least 5 days of each week.

19. The method of claim 8 , wherein for a duration of 6 weeks following administration of the first dose of temozolomide, the glioma is subjected to radiation therapy once per day for 5 days each week.

20. The method of claim 18 , wherein when radiation therapy is administered to the glioma, the amount of radiation provided to the glioma on the day of administering the radiation therapy is from about 1 Gy to about 3 Gy.

21. The method of claim 18 , wherein when radiation therapy is administered to the glioma, the amount of radiation provided to the glioma on the day of administering the radiation therapy is about 2 Gy.

22. The method of claim 18 , wherein the glioma is exposed to from about 50 Gy to about 70 Gy of radiation by the radiation therapy over a period of 6 weeks following administration of the first dose of temozolomide.

23. The method of claim 18 , wherein the radiation therapy is (i) conventional fractionated external beam radiation or (ii) intensity-modulated radiation therapy.

24. The method of claim 18 , wherein after receiving temozolomide for a duration of 6 weeks, the patient does not receive any of temozolomide, radiation therapy, or ABDNAZ for a duration of at least about 4 weeks.

25. The method of claim 24 , wherein the patient after having not received any of temozolomide, radiation therapy, or ABDNAZ for a duration of at least about 4 weeks, then receives (i) a therapeutically effective amount of a formulation comprising temozolomide on at least five consecutive days during the first week of each 28 day period, and (ii) a therapeutically effective amount of a formulation comprising ABDNAZ at least once per week for a duration of at least 4 months.

26. The method of claim 25 , wherein after the duration over which the patient has not received any of temozolomide, radiation therapy, or ABDNAZ, the formulation comprising temozolomide is administered orally to the patient to provide temozolomide in an amount of at least 150 mg/m 2 .

27. The method of claim 25 , wherein after the duration over which the patient has not received any of temozolomide, radiation therapy, or ABDNAZ, the formulation comprising ABDNAZ is administered to the patient by intravenous infusion providing ABDNAZ in an amount of about 5 mg/m 2 .

28. The method of claim 18 , wherein the patient has previously undergone surgery, to remove at least some glioma tissue, within six weeks prior to receiving the first dose of temozolomide.

29. A method of treating a glioma in a patient, comprising the steps of:
(a) administering to the patient in need thereof a therapeutically effective amount of a formulation comprising irinotecan, and within about 7 days subjecting the glioma to radiation therapy; and
(b) administering to the patient at least one dose of a therapeutically effective amount of a formulation comprising ABDNAZ within about 7 days of administration of a first dose of the irinotecan; to treat the glioma.

30. The method of claim 18 , wherein the glioma is an astrocytoma.

31. The method of claim 18 , wherein the glioma is a malignant astrocytoma.

32. The method of claim 18 , wherein the glioma is a glioblastoma.

33. The method of claim 18 , wherein the patient is an adult human.

34. The method of claim 18 , wherein there is at least a 35% reduction in the size of at least one glioma tumor in the patient.

35. The method of claim 18 , wherein there is at least a 35% reduction in the number of glioma tumors in the patient.

Assignees

• Epicentrx Inc
• Epicentrix Inc

Inventors

• Oronsky Bryan T
• Scicinski Jan

Classifications

• A61K31/4745

  condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48) · CPC title

• A61K31/397

  having four-membered rings, e.g. azetidine · CPC title

• A61K31/495 Primary

  having six-membered rings with two {or more} nitrogen atoms as the only ring heteroatoms, e.g. piperazine {or tetrazines}(A61K31/48 takes precedence {; with three nitrogen atoms A61K31/53}) · CPC title

• A61K9/0053

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title

• A61N5/10

  X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy (A61N5/01 takes precedence) · CPC title