Clinical trial NCT01055678: To Evaluate the Characteristics of a Breast Cancer
Official title: Pilot Study to Characterize the HRHV Axis in the Microenvironment of Breast Cancers
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: EARLY_PHASE1
Conditions: Breast Cancer
Keywords: breast cancer
ductal breast carcinoma in situ
breast cancer in situ
invasive carcinoma
invasive ductal carcinoma
invasive lobular carcinoma
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Cancer Institute (NCI)
First posted: 2010-01-26
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: To evaluate tumor characteristics
timeFrame: 2 years
Secondary outcomes:
measure: Intra and Interpatient correlations with tumor hypoxia
timeFrame: 3 years
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: Mark W Dewhirst, DVM, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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. doi: 10.1007/s002800100324.