To Evaluate the Characteristics of a Breast Cancer

NCT01055678 | Withdrawn Early Phase 1

• 2 other identifiers: Pro00020382R01CA040355
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer

Keywords

breast cancer; ductal breast carcinoma in situ; breast cancer in situ; invasive carcinoma; invasive ductal carcinoma; invasive lobular carcinoma

Outcome Measures

Primary Outcomes (1)

• To evaluate tumor characteristics

  2 years

Secondary Outcomes (1)

• Intra and Interpatient correlations with tumor hypoxia

  3 years

Study Arms (1)

All Patients

EXPERIMENTAL

Single arm study analyzing tumor hypoxia after EF5 injection

Drug: EF5; Procedure: Partial or Total Mastectomy

Interventions

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.

All Patients

Partial or Total Mastectomy PROCEDURE

A small tissue sample will be removed from the excised tissue and will be stored for later analysis.

All Patients

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mark Dewhirst: lead
• National Institutes of Health (NIH): collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related 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.

  PMID: 18500244 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.

  PMID: 11592338 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Breast Carcinoma In Situ; Carcinoma, Lobular

Interventions

Mastectomy, Simple

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Carcinoma in Situ; Neoplasms, Ductal, Lobular, and Medullary

Intervention Hierarchy (Ancestors)

Mastectomy; Surgical Procedures, Operative

Study Officials

• Mark W Dewhirst, DVM, PhD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 24, 2010
• First Posted: January 26, 2010
• Study Start: January 1, 2010
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: December 17, 2012

Record last verified: 2012-12

Locations

US (1)