IRS Proteins and Trastuzumab Resistance

NCT00657345 | Completed

• 1 other identifier: UM200801
• Study Type: observational
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

Significant progress has been made in the treatment of women with Her2 positive breast cancer who are treated with trastuzumab, a humanized monoclonal antibody that inhibits Her2. Despite this progress not all patients with Her2 positive metastatic breast cancer respond to trastuzumab and patients with metastatic disease who do respond usually develop progressive disease during treatment with trastuzumab. The mechanism of such resistance is unknown. We propose to investigate the mechanism of trastuzumab resistance in Her2 positive breast cancer. The hypothesis to be examined in the basic science section of this study is that IRS-1 and IRS-2 are modifiers of HER2 signaling and that these adapter proteins could be predictive indicators of treatment response to Herceptin in patients that are candidates for this targeted therapy. The connection between IRS-1 and IRS-2 expression and Herceptin response and clinical outcome in HER2 positive human breast tumors will be evaluated to determine if IRS expression correlates with resistance to Herceptin therapy and with the aggressive behavior of these tumors. This study will establish if the IRS proteins influence HER2 function in tumors and if they are predictive markers for evaluating treatment options for HER2 positive patients.

Conditions

Breast Cancer

Keywords

trastuzumab; breast cancer; her2 positive breast cancer

Outcome Measures

Primary Outcomes (1)

• A tissue acquisition and collection protocol that will analyze potential cellular changes that occur after treatment with trastuzumab to try to elucidate the mechanism of trastuzumab resistance in patients with HER2-positive breast cancer.

  2-years

Study Arms (1)

1

This is a tissue acquisition and collection protocol that will analyze potential cellular changes that occur after treatment with trastuzumab.

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Women age 18-70 with breast cancer

You may qualify if:

• Women age 18-70 with breast cancer who have signed an IRB approved consent form.
• Biopsy proven breast cancer with her 2 overexpression by fluorescence in situ hybridization (FISH).
• Newly diagnosed patients with Stages 1,2 and 3 breast cancer who will be receiving neoadjuvant chemotherapy prior to breast surgery
• Normal Left ventricular ejection fraction, as measured by echocardiogram or MUGA scan
• Normal bone marrow, kidney and liver function
• No evidence of distant metastatic disease

You may not qualify if:

• Patients with significant cardiac disease including abnormal LVEF, symptomatic coronary artery disease, uncontrolled hypertension.
• Prior treatment with chemotherapy.
• Any cancer other than previously treated skin cancer.
• Breast cancer in a previously irradiated breast.

Sponsors & Collaborators

• University of Massachusetts, Worcester: lead

Study Sites (1)

University of Mass Medical School

Worcester, Massachusetts, 01655, United States

Location

Related Publications (3)

• Mohsin SK, Weiss HL, Gutierrez MC, Chamness GC, Schiff R, Digiovanna MP, Wang CX, Hilsenbeck SG, Osborne CK, Allred DC, Elledge R, Chang JC. Neoadjuvant trastuzumab induces apoptosis in primary breast cancers. J Clin Oncol. 2005 Apr 10;23(11):2460-8. doi: 10.1200/JCO.2005.00.661. Epub 2005 Feb 14.

  PMID: 15710948 BACKGROUND

• Hurley J, Doliny P, Reis I, Silva O, Gomez-Fernandez C, Velez P, Pauletti G, Powell JE, Pegram MD, Slamon DJ. Docetaxel, cisplatin, and trastuzumab as primary systemic therapy for human epidermal growth factor receptor 2-positive locally advanced breast cancer. J Clin Oncol. 2006 Apr 20;24(12):1831-8. doi: 10.1200/JCO.2005.02.8886. Epub 2006 Mar 20.

  PMID: 16549824 BACKGROUND

• Coudert BP, Largillier R, Arnould L, Chollet P, Campone M, Coeffic D, Priou F, Gligorov J, Martin X, Trillet-Lenoir V, Weber B, Bleuse JP, Vasseur B, Serin D, Namer M. Multicenter phase II trial of neoadjuvant therapy with trastuzumab, docetaxel, and carboplatin for human epidermal growth factor receptor-2-overexpressing stage II or III breast cancer: results of the GETN(A)-1 trial. J Clin Oncol. 2007 Jul 1;25(19):2678-84. doi: 10.1200/JCO.2006.09.9994. Epub 2007 May 21.

  PMID: 17515572 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Kathryn L Edmiston, MD

  University of Massachusetts, Worcester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 8, 2008
• First Posted: April 14, 2008
• Study Start: March 1, 2008
• Primary Completion: February 1, 2013
• Study Completion: February 1, 2013
• Last Updated: November 5, 2013

Record last verified: 2013-11

Locations

US (1)