To Evaluate the Characteristics of a Breast Cancer

Breast Cancer Clinical Trial

Official title:

Pilot Study to Characterize the HRHV Axis in the Microenvironment of Breast Cancers

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01055678
• Other study ID #: Pro00020382
• Secondary ID: R01CA040355
• Status: Withdrawn
• Phase: Phase 0
• First received: January 24, 2010
• Last updated: December 14, 2012
• Start date: January 2010
• Est. completion date: December 2011

Study information

• Verified date: December 2012
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed Stage 0 - III invasive carcinoma of the breast

• Tumor size greater than 1-cm by radiological (mammogram/ultrasound or MRI) evaluation

• KPS status = 70

• Bilirubin = 1.5x normal

• Creatinine = 1.8

• WBC > 3000/mm^3 and platelets > 100,000/mm^3

Exclusion Criteria:

• Pregnant or breast-feeding women

• Neoadjuvant chemo or hormonal therapy for existent breast malignancy

• Allergy to IV contrast dye

• History of grade III or IV peripheral neuropathy as defined by the NCI CTC

• Previous history of any malignancy treated with radiotherapy and/or chemohormonal therapy

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• EF5
An infusion of EF5, a fluorinated 2-nitroimidazole, will be administered using the recommended dose of 21mg/kg one day prior to surgical procedure.

Procedure:
• Partial or Total Mastectomy
A small tissue sample will be removed from the excised tissue and will be stored for later analysis.

Locations

Country	Name	City	State
United States	Duke University Medical Center	Durham	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
Mark Dewhirst	National Cancer Institute (NCI), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. Review. Erratum in: Nat Rev Cancer. 2008 Aug;8(8):654. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate tumor characteristics		2 years	Yes
Secondary	Intra and Interpatient correlations with tumor hypoxia		3 years	Yes