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| ID | Type | Description | Link |
|---|---|---|---|
| R01CA040355 | U.S. NIH Grant/Contract | View source |
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PI left Duke
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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
| National Cancer Institute (NCI) | NIH |
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The purpose of this pilot study is to determine the prevalence of markers of chronic and cycling hypoxia and reactive species stress (oxidative and nitrosative) in the breast cancer tumor microenvironment. The study is based around four cornerstone features of the pathologic microenvironment - Hypoxia, Reactive Species (reactive oxygen and nitrogen species), HIF-1 and VEGF, which we term the HRHV axis. Fifty breast cancer patients with planned surgical excision will be administered the hypoxia marker drug, EF5, 24-36 hr prior to surgical excision. EF5 is a non-therapeutic drug and provides no direct benefit to those patients enrolled in this pilot study. Tissues obtained intra-operatively will be snap frozen and subsequently analyzed for EF5 binding. Immunohistochemical analysis of a cohort of immunohistochemical and urine markers that depict the HRHV axis will be examined. The association of the markers with the presence of hypoxia, as determined by EF5 positivity, will be determined. Data from this pilot study will be used to establish the prevalence of markers of the HRHV axis in breast cancer. This information will be crucial for future human trials in which the HRHV axis is therapeutically targeted.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| All Patients | Experimental | Single arm study analyzing tumor hypoxia after EF5 injection |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| EF5 | Drug | An infusion of EF5, a fluorinated 2-nitroimidazole, will be administered using the recommended dose of 21mg/kg one day prior to surgical procedure. |
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| Measure | Description | Time Frame |
|---|---|---|
| To evaluate tumor characteristics | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Intra and Interpatient correlations with tumor hypoxia | 3 years |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mark W Dewhirst, DVM, PhD | Duke University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Duke University Medical Center | Durham | North Carolina | 27710 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18500244 | Background | Dewhirst MW, Cao Y, Moeller B. Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response. Nat Rev Cancer. 2008 Jun;8(6):425-37. doi: 10.1038/nrc2397. | |
| 11592338 | Background | Koch CJ, Hahn SM, Rockwell K Jr, Covey JM, McKenna WG, Evans SM. Pharmacokinetics of EF5 [2-(2-nitro-1-H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl) acetamide] in human patients: implications for hypoxia measurements in vivo by 2-nitroimidazoles. Cancer Chemother Pharmacol. 2001 Sep;48(3):177-87. doi: 10.1007/s002800100324. |
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| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D002285 | Carcinoma, Intraductal, Noninfiltrating |
| D000071960 | Breast Carcinoma In Situ |
| D018275 | Carcinoma, Lobular |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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| ID | Term |
|---|---|
| D015413 | Mastectomy, Simple |
| ID | Term |
|---|---|
| D008408 | Mastectomy |
| D013514 | Surgical Procedures, Operative |
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| Partial or Total Mastectomy | Procedure | A small tissue sample will be removed from the excised tissue and will be stored for later analysis. |
|
| D017437 |
| Skin and Connective Tissue Diseases |
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D002278 | Carcinoma in Situ |
| D018299 | Neoplasms, Ductal, Lobular, and Medullary |