CA2708229A1 - Treatment of melanoma with alpha thymosin peptides in combination with a kinase inhibitor - Google Patents
Treatment of melanoma with alpha thymosin peptides in combination with a kinase inhibitor Download PDFInfo
- Publication number
- CA2708229A1 CA2708229A1 CA2708229A CA2708229A CA2708229A1 CA 2708229 A1 CA2708229 A1 CA 2708229A1 CA 2708229 A CA2708229 A CA 2708229A CA 2708229 A CA2708229 A CA 2708229A CA 2708229 A1 CA2708229 A1 CA 2708229A1
- Authority
- CA
- Canada
- Prior art keywords
- day
- sorafenib
- group
- melanoma
- tumor
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 201000001441 melanoma Diseases 0.000 title claims abstract description 41
- 108010046075 Thymosin Proteins 0.000 title claims abstract description 32
- 229940043355 kinase inhibitor Drugs 0.000 title claims abstract description 23
- 239000003757 phosphotransferase inhibitor Substances 0.000 title claims abstract description 23
- 238000011282 treatment Methods 0.000 title description 35
- 102000007501 Thymosin Human genes 0.000 title description 3
- 238000011269 treatment regimen Methods 0.000 claims abstract description 26
- 206010027476 Metastases Diseases 0.000 claims abstract description 7
- 230000009401 metastasis Effects 0.000 claims abstract description 5
- 238000002648 combination therapy Methods 0.000 claims abstract description 3
- 108010078233 Thymalfasin Proteins 0.000 claims description 134
- 102400000800 Thymosin alpha-1 Human genes 0.000 claims description 134
- NZVYCXVTEHPMHE-ZSUJOUNUSA-N thymalfasin Chemical compound CC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O NZVYCXVTEHPMHE-ZSUJOUNUSA-N 0.000 claims description 133
- 229960004231 thymalfasin Drugs 0.000 claims description 132
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 claims description 109
- 239000005511 L01XE05 - Sorafenib Substances 0.000 claims description 108
- 229960003787 sorafenib Drugs 0.000 claims description 108
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 claims description 65
- 238000000034 method Methods 0.000 claims description 26
- 239000002295 alkylating antineoplastic agent Substances 0.000 claims description 8
- 230000004580 weight loss Effects 0.000 claims description 8
- 231100000419 toxicity Toxicity 0.000 claims description 6
- 230000001988 toxicity Effects 0.000 claims description 6
- 229960003901 dacarbazine Drugs 0.000 claims description 4
- 206010028980 Neoplasm Diseases 0.000 description 61
- 239000003981 vehicle Substances 0.000 description 34
- 241001465754 Metazoa Species 0.000 description 33
- 230000037396 body weight Effects 0.000 description 33
- 239000003814 drug Substances 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 12
- 229940079593 drug Drugs 0.000 description 10
- 230000005764 inhibitory process Effects 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- 241000699670 Mus sp. Species 0.000 description 8
- 230000000259 anti-tumor effect Effects 0.000 description 8
- 230000034994 death Effects 0.000 description 8
- 231100000517 death Toxicity 0.000 description 8
- 231100000331 toxic Toxicity 0.000 description 8
- 230000002588 toxic effect Effects 0.000 description 8
- 230000004614 tumor growth Effects 0.000 description 8
- 208000001382 Experimental Melanoma Diseases 0.000 description 6
- 238000002512 chemotherapy Methods 0.000 description 6
- 239000002953 phosphate buffered saline Substances 0.000 description 6
- 238000007920 subcutaneous administration Methods 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 150000001413 amino acids Chemical group 0.000 description 5
- 238000011740 C57BL/6 mouse Methods 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 229910002092 carbon dioxide Inorganic materials 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 241001529936 Murinae Species 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 208000000453 Skin Neoplasms Diseases 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 230000002238 attenuated effect Effects 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 238000009169 immunotherapy Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 201000000849 skin cancer Diseases 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 208000013641 Cerebrofacial arteriovenous metameric syndrome Diseases 0.000 description 2
- 238000011887 Necropsy Methods 0.000 description 2
- 229920002685 Polyoxyl 35CastorOil Polymers 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 230000036765 blood level Effects 0.000 description 2
- 229940044683 chemotherapy drug Drugs 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000002513 implantation Methods 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- QUANRIQJNFHVEU-UHFFFAOYSA-N oxirane;propane-1,2,3-triol Chemical compound C1CO1.OCC(O)CO QUANRIQJNFHVEU-UHFFFAOYSA-N 0.000 description 2
- 239000008389 polyethoxylated castor oil Substances 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 108700016958 thymosin fraction 5 Proteins 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 206010003497 Asphyxia Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 206010027480 Metastatic malignant melanoma Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 201000005969 Uveal melanoma Diseases 0.000 description 1
- 238000009098 adjuvant therapy Methods 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229940034982 antineoplastic agent Drugs 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 230000005773 cancer-related death Effects 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 238000011254 conventional chemotherapy Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 230000002584 immunomodulator Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 210000002752 melanocyte Anatomy 0.000 description 1
- 208000021039 metastatic melanoma Diseases 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/2292—Thymosin; Related peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Endocrinology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US1347607P | 2007-12-13 | 2007-12-13 | |
| US61/013,476 | 2007-12-13 | ||
| PCT/US2008/086545 WO2009076587A1 (en) | 2007-12-13 | 2008-12-12 | Treatment of melanoma with alpha thymosin peptides in combination with a kinase inhibitor |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2708229A1 true CA2708229A1 (en) | 2009-06-18 |
Family
ID=40755899
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2708229A Abandoned CA2708229A1 (en) | 2007-12-13 | 2008-12-12 | Treatment of melanoma with alpha thymosin peptides in combination with a kinase inhibitor |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US20100267637A1 (https=) |
| EP (1) | EP2240194A4 (https=) |
| JP (1) | JP2011506473A (https=) |
| CN (1) | CN101945664A (https=) |
| AR (1) | AR069769A1 (https=) |
| AU (1) | AU2008335025A1 (https=) |
| CA (1) | CA2708229A1 (https=) |
| WO (1) | WO2009076587A1 (https=) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP6821560B2 (ja) | 2014-10-21 | 2021-01-27 | サイクロン ファーマシューティカルズ インターナショナル エルティーディー．Ｓｃｉｃｌｏｎｅ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｔｅｒｎａｔｉｏｎａｌ Ｌｔｄ． | 免疫刺激剤による癌治療 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2604845A1 (de) * | 1976-02-07 | 1977-08-18 | Knoll Ag | Neue piperazinderivate |
| EP2641611A3 (en) * | 2003-10-17 | 2013-12-18 | Novo Nordisk A/S | Combination therapy |
| US20070292392A1 (en) * | 2006-06-15 | 2007-12-20 | Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. | Use of thymosin alpha 1 for preparing a medicament for the treatment of stage iv malignant melanoma |
-
2008
- 2008-12-12 US US12/747,438 patent/US20100267637A1/en not_active Abandoned
- 2008-12-12 CA CA2708229A patent/CA2708229A1/en not_active Abandoned
- 2008-12-12 EP EP08858909A patent/EP2240194A4/en not_active Withdrawn
- 2008-12-12 JP JP2010538181A patent/JP2011506473A/ja active Pending
- 2008-12-12 WO PCT/US2008/086545 patent/WO2009076587A1/en not_active Ceased
- 2008-12-12 AU AU2008335025A patent/AU2008335025A1/en not_active Abandoned
- 2008-12-12 CN CN2008801268138A patent/CN101945664A/zh active Pending
- 2008-12-15 AR ARP080105451A patent/AR069769A1/es not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| EP2240194A4 (en) | 2011-12-21 |
| AR069769A1 (es) | 2010-02-17 |
| WO2009076587A1 (en) | 2009-06-18 |
| AU2008335025A1 (en) | 2009-06-18 |
| EP2240194A1 (en) | 2010-10-20 |
| CN101945664A (zh) | 2011-01-12 |
| US20100267637A1 (en) | 2010-10-21 |
| JP2011506473A (ja) | 2011-03-03 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20141212 |