| Title: |
Therapeutic regimen for treating cancer |
| Document Number: |
20060257369 |
| Publication Date: |
November 16, 2006 |
| Appl. No: |
11/432943 |
| Application Filed: |
May 12, 2006 |
| Abstract: |
The invention provides a method for treating cancer in a human comprising (a) administering to the human a dose of a pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier and (ii) an adenoviral vector comprising a nucleic acid sequence encoding a human TNF-α and operably linked to a promoter, wherein the dose comprises about 4×107 to about 4×1012 particle units (pu) of adenoviral vector, at least once in a therapeutic period comprising up to about 10 weeks, (b) administering a dose of ionizing radiation to the human over the duration of the therapeutic period, and (c) administering a dose of one or more chemotherapeutics to the human over the duration of the therapeutic period, whereby the cancer in the human is treated. |
| Inventors: |
Kessler, Paul D. (Hagerstown, MD, US); Rasmussen, Henrik S. (Arnold, MD, US); Chu, Karen W. (White Plains, NY, US) |
| Assignees: |
GenVec, Inc. (Gaithersburg, MD, US) |
| Claim: |
1. A method for treating cancer in a human, wherein the cancer is selected from the group consisting of unresectable, locally advanced pancreatic cancer (LAPC), locally advanced resectable esophageal cancer, and locally advanced resectable rectal cancer, which method comprises: (a) administering to the human a dose of a pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier and (ii) an adenoviral vector comprising a nucleic acid sequence encoding a human TNF-α and operably linked to a promoter, wherein the dose comprises about 4×107 to about 4×1012 particle units (pu) of adenoviral vector, at least once in a therapeutic period comprising up to about 10 weeks, (b) administering a dose of ionizing radiation to the human over the duration of the therapeutic period, and (c) administering a dose of one or more chemotherapeutics to the human over the duration of the therapeutic period, whereby the unresectable, locally advanced pancreatic cancer, the locally advanced resectable esophageal cancer, or the locally advanced resectable rectal cancer in the human is treated. |
| Claim: |
2. The method of claim 1, wherein the adenoviral vector, the dose of ionizing radiation, and the dose of the one or more chemotherapeutics are administered to the human concurrently over the duration of the therapeutic period. |
| Claim: |
3. The method of claim 1, wherein the pharmaceutical composition contacts a tumor, and tumor cells within the tumor are destroyed. |
| Claim: |
4. The method of claim 3, wherein the size of the tumor is reduced. |
| Claim: |
5. The method of claim 1, wherein the adenoviral vector is replication-deficient. |
| Claim: |
6. The method of claim 5, wherein the promoter is an inducible promoter. |
| Claim: |
7. The method of claim 6, wherein the promoter is chemo-inducible. |
| Claim: |
8. The method of claim 6, wherein the promoter is radiation-inducible. |
| Claim: |
9. The method of claim 8, wherein the radiation-inducible promoter is the EGR-1 promoter. |
| Claim: |
10. The method of claim 3, wherein a dose of pharmaceutical composition is administered to the tumor about once a week in a therapeutic period comprising about three to seven weeks. |
| Claim: |
11. The method of claim 3, wherein the therapeutic period comprises up to six weeks, and the method comprises administering one dose of pharmaceutical composition in each week of the therapeutic period. |
| Claim: |
12. The method of claim 3, wherein the pharmaceutical composition is administered to the tumor by percutaneous transabdominal administration, endoscopic administration, or by endoscopic ultrasound-guided administration. |
| Claim: |
13. The method of claim 3, wherein the pharmaceutical composition is administered to the tumor via 2-5 injections. |
| Claim: |
14. The method of claim 1, wherein the dose of ionizing radiation comprises about 40 Gray (Gy) to about 60 Gy administered over the duration of the therapeutic period. |
| Claim: |
15. The method of claim 14, wherein the method comprises administering one fraction of the dose of ionizing radiation per day for five days in each week of the therapeutic period. |
| Claim: |
16. The method of claim 15, wherein the fraction of the dose of ionizing radiation comprises about 1-2 Gy. |
| Claim: |
17. The method of claim 15, wherein the fraction of the dose of ionizing radiation is administered to the human at least four hours after administration of the pharmaceutical composition. |
| Claim: |
18. The method of claim 1, wherein the one or more chemotherapeutics are selected from the group consisting of adriamycin, asparaginase, bleomycin, busulphan, cisplatin, carboplatin, carmustine, capecitabine, chlorambucil, cytarabine, cyclophosphamide, camptothecin, dacarbazine, dactinomycin, daunorubicin, dexrazoxane, docetaxel, doxorubicin, etoposide, floxuridine, fludarabine, fluorouracil, gemcitabine, hydroxyurea, idarubicin, ifosfamide, irinotecan, lomustine, mechlorethamine, mercaptopurine, meplhalan, methotrexate, mitomycin, mitotane, mitoxantrone, nitrosurea, paclitaxel, pamidronate, pentostatin, plicamycin, procarbazine, rituximab, streptozocin, teniposide, thioguanine, thiotepa, vinblastine, vincristine, vinorelbine, taxol, transplatinum, and 5-fluorouracil. |
| Claim: |
19. The method of claim 18, wherein the one or more chemotherapeutics are selected from the group consisting of 5-fluorouracil, capecitabine, and cisplatin, or combinations thereof. |
| Claim: |
20. The method of claim 19, wherein the chemotherapeutic is 5-fluoruracil. |
| Claim: |
21. The method of claim 20, wherein the dose of 5-fluorouracil comprises about 100 mg/m2/day to about 300 mg/m2/day. |
| Claim: |
22. The method of claim 19, wherein the chemotherapeutic is capecitabine. |
| Claim: |
23. The method of claim 22, wherein the dose of capecitabine comprises about 800 mg/m2/day to about 1000 mg/m2/day. |
| Claim: |
24. The method of claim 19, wherein the therapeutic period comprises five weeks and the method comprises administering about 50-100 mg/m2 of cisplatin and about 900-1100 mg/m2 of 5-fluorouracil beginning on each of two separate days of the therapeutic period. |
| Claim: |
25. The method of claim 24, wherein the method comprises administering about 75 mg/m2 of cisplatin and about 1000 mg/m2 of 5-fluoruracil beginning on day 1 and day 29 of the therapeutic period. |
| Claim: |
26. The method of claim 18, wherein the one or more chemotherapeutic agents are administered within 24 hours of the administration of the dose of ionizing radiation. |
| Claim: |
27. The method of claim 3, wherein the method further comprises surgical resection of the tumor after completion of the therapeutic period. |
| Claim: |
28. The method of claim 27, wherein the method comprises surgical resection of the tumor. 4-10 weeks after completion of the therapeutic period. |
| Claim: |
29. The method of claim 28, wherein the method comprises surgical resection of the tumor 3-6 weeks after completion of the therapeutic period. |
| Claim: |
30. The method of claim 29, wherein the method comprises administering adjuvant chemotherapy following surgical resection of the tumor. |
| Claim: |
31. The method of claim 30, wherein the adjuvant chemotherapy is administered 2-4 weeks following surgical resection of the tumor. |
| Claim: |
32. The method of claim 1, which method further comprises administering a dose of an H2 blocker or a proton pump inhibitor. |
| Claim: |
33. The method of claim 14, wherein the method further comprises administering a booster dose of ionizing radiation comprising about 5-10 Gy to the tumor. |
| Claim: |
34. The method of claim 1, wherein the cancer is locally advanced resectable rectal cancer. |
| Claim: |
35. The method of claim 34, wherein the stage of the locally advanced resectable rectal cancer is T3 or T4. |
| Claim: |
36. The method of claim 34, whereby the treatment of the locally advanced resectable rectal cancer is evidenced by the resected tumor comprising a necrosis percentage of at least about 90%. |
| Claim: |
37. The method of claim 34, whereby the treatment of the locally advanced resectable rectal cancer is evidenced by at least a 10% decrease in the carcinoembryonic antigen (CEA) level at 4-12 weeks after completion of the therapeutic period as compared to the CEA level before the therapeutic period. |
| Claim: |
38. The method of claim 1, wherein the cancer is locally advanced resectable esophageal cancer. |
| Claim: |
39. The method of claim 38, wherein the stage of the locally advanced resectable esophageal cancer is stage III or stage IV. |
| Claim: |
40. The method of claim 1, whereby the treatment of the locally advanced resectable esophageal cancer or the locally advanced rectal cancer is evidenced by the lack of tumor tissue in the resected tissue. |
| Claim: |
41. The method of claim 1, wherein the cancer is unresectable, locally advanced pancreatic cancer. |
| Claim: |
42. The method of claim 41, whereby the treatment of the unresectable, locally advanced pancreatic cancer is evidenced by about a 25% to 50% reduction in the size of the tumor for at least four weeks after completion of therapeutic period as compared to the area of the tumor before the therapeutic period. |
| Claim: |
43. The method of claim 41, whereby the treatment of the unresectable, locally advanced pancreatic cancer is evidenced by at least about a 50% reduction in the size of the tumor for at least four weeks after completion of the therapeutic period as compared to the area of the tumor before the therapeutic period. |
| Claim: |
44. The method of claim 41, whereby the treatment of the unresectable, locally advanced pancreatic cancer is evidenced by disappearance of the tumor that is sustained for at least four weeks. |
| Claim: |
45. The method of claim 41, whereby the treatment of the unresectable, locally advanced pancreatic cancer is evidenced by at least a 10% decrease in the CA19-9 tumor antigen level at 4-12 weeks after completion of the therapeutic period as compared to the CA19-9 tumor antigen level before the therapeutic period. |
| Claim: |
46. The method of claim 41, whereby the treatment of the unresectable, locally advanced pancreatic cancer is evidenced by the conversion of the surgical stage of the tumor from unresectable to resectable at 12 weeks after completion of the therapeutic period. |
| Claim: |
47. The method of claim 41, whereby the treatment of the unresectable, locally advanced pancreatic cancer is evidenced by at least a 50% decrease in pain intensity as assigned by the Clinical Benefit Response Criteria for any consecutive four-week period in the 12 weeks after completion of the therapeutic period as compared to the pain intensity before the therapeutic period. |
| Claim: |
48. The method of claim 41, whereby the treatment of the unresectable, locally advanced pancreatic cancer is evidenced by at least a 50% decrease in analgesic consumption as assigned by the Clinical Benefit Response Criteria for any four consecutive four week period in the 12 weeks after completion of the therapeutic period as compared to the analgesic consumption before the therapeutic period. |
| Claim: |
49. The method of claim 41, whereby the treatment of the unresectable, locally advanced pancreatic cancer is evidenced by at least a 20 point increase in the Karnofsky Performance Scale score as assigned by the Clinical Benefit Response Criteria for any consecutive four week period in the 12 weeks after completion of the therapeutic period as compared to the score before the therapeutic period. |
| Claim: |
50. A method of treating glioma in a human comprising: (a) administering to the human a dose of a pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier and (ii) an adenoviral vector comprising a nucleic acid sequence encoding a human TNF-α and operably linked to a promoter, wherein the dose comprises about 4×107 to about 4×1012 particle units (pu) of adenoviral vector, at least once in a therapeutic period comprising up to about 10 weeks, and (b) administering a dose of ionizing radiation to the human over the duration of the therapeutic period, whereby the glioma in the human is treated. |
| Claim: |
51. The method of claim 50, wherein the glioma is recurrent glioblastoma multiforme. |
| Claim: |
52. The method of claim 50, wherein the dose of ionizing radiation comprises about 10 Gray (Gy) to about 40 Gy administered over the duration of the therapeutic period. |
| Claim: |
53. The method of claim 52, wherein the method comprises administering one fraction of the dose of ionizing radiation per day. |
| Claim: |
54. The method of claim 53, wherein the fraction of the dose of ionizing radiation comprises about 4-5 Gy. |
| Claim: |
55. The method of claim 53, wherein the fraction of the dose of ionizing radiation is administered to the human at least three days after administration of the pharmaceutical composition. |
| Current U.S. Class: |
424093/200 |
| Current International Class: |
61; 61 |
| Accession Number: |
edspap.20060257369 |
| Database: |
USPTO Patent Applications |
