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MIRNA Profiling of Breast Cancer in Patients Undergoing Neoadjuvant or Adjuvant Treatment for Locally Advanced & Inflammatory Breast Cancer

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ClinicalTrials.gov Identifier: NCT01231386
Recruitment Status : Recruiting
First Posted : November 1, 2010
Last Update Posted : August 22, 2017
Information provided by (Responsible Party):

Study Description
Brief Summary:
MicroRNAs (MiRNAs) regulate the translation of RNAs and are implicated in cell proliferation and renewal both under physiologically normal as well as in malignant conditions. Dysregulation of specific miRNAs may be associated with either gaining oncogenic or loosing tumor suppressing functions. MiRNA dysregulation has been implicated in breast cancer tumorigenic (stem cell) and non-tumorigenic development. Therefore, miRNA profiling of treatment naïve and treatment-exposed breast tumors and sequential samples of blood/serum will allow for identification of miRNA markers of prognosis and as indicators and potential targets for personalized therapies. In this proposal, specimens from patients treated in the clinical breast cancer program on already existing protocols (IRB 05091 and 05015) will be characterized by Dr. Rossi's laboratory and collaborators, and the information gained will be applied to develop specific therapies.

Condition or disease
Breast Cancer

Detailed Description:

Current neoadjuvant or adjuvant treatment strategies do not allow for rationale incorporation of such agents. One needs tools to predict both de novo and acquired resistance to therapeutic agents. This is a difficult task, due to the compound nature of escape routes: tumor exposure is usually to a combination of therapeutic agents and the mechanisms of resistance are broad: intrinsic resistance due to existing mutations, or regulatory - miRNA, other epigenetic - alterations, polymorphisms, tumor cell adaptation via new mutations and activation of alternative pathways, lack of optimal pharmacokinetics/genomics, activation of efflux mechanisms, accelerated repair mechanisms are involved.

Similarly, not all patients who are candidates for primary surgical intervention to be followed by post-operative adjuvant therapy benefit from such systemic treatments. The mechanisms of resistance be it de novo in surviving stem cell/tumorigenic components, or acquired by cells left behind "dormant" after the surgical intervention, are not well delineated.

Breast tumors subjected to neoadjuvant chemotherapy allow for baseline and treatment-effected sampling. Characterization of core biopsy specimens of primary tumors procured prior to exposure to neoadjuvant therapy from different varieties of breast cancer subtypes, and of subsequent mid-treatment and intraoperative (procured during definitive surgery following completion of neoadjuvant therapy) samples should help to assess the predictive value of the pre-treatment and post-treatment miRNA expression profile for complete and near complete response, as a surrogate marker for survival. Similarly, patterns of de novo and acquired resistance may emerge when assessment of pre- and post treatment miRNA expression profiles are analyzed in a supervised manner of classification using pathological response as classifier. Samples obtained from patients with primary surgical removal of their tumors before any systemic treatment exposure on the other hand, will allow for determining markers of prognosis, and predictors for response to therapeutic targeting agents.

Time Perspective: Retrospective/Prospective

Study Design

Study Type : Observational
Estimated Enrollment : 165 participants
Observational Model: Cohort
Time Perspective: Other
Official Title: MIRNA Profiling of Breast Cancer in Patients Undergoing Neoadjuvant or Adjuvant Treatment for Locally Advanced & Inflammatory Breast Cancer
Study Start Date : November 2009
Estimated Primary Completion Date : May 2018
Estimated Study Completion Date : May 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
U.S. FDA Resources

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :
  1. Performance of miRNA profiling from tumor samples from primary breast tumors [ Time Frame: 3 years after completion of sample collection ]
  2. Assessment of miRNA profiles from blood/serum samples from patients at baseline, and if feasible, at different time points [ Time Frame: 3 years after completion of sample collection ]
  3. Analysis of miRNA findings and correlate miRNA patterns of expression in tumor, lymph nodes -if available- and in serum [ Time Frame: 3 years after competion of sample collection ]
  4. Correlation of classic tumor markers such as estrogen and progesterone receptor (ER,PR), and HER2 expression with tumor stage and grade [ Time Frame: 3 years after completion of sample collection ]
  5. Determination of specific miRNA functions [ Time Frame: 3 years after completion of sample collection ]
  6. Determination of ability to knock down functionally relevant overexpressed miRNAs by miR-sponge/antagomirs [ Time Frame: 3 years after completion of sample collection ]
  7. Design of prospective pilot phase I-II trials to interfere with dysfunctional/dysregulated miRNA expression [ Time Frame: 3 years after completion of sample collection ]

Biospecimen Retention:   Samples With DNA
Tissue and Blood Procurement. Breast cancer tissues from core biopsies (as available, preferably fresh frozen or RNA-later preserved, but in case of lack of availability, formalin-fixed paraffin-embedded [FFPE] core or tissue samples) which have been collected or will be collected under IRB#05091 or 05015.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Female, Breast Cancer, > 18 years, regardless of histology, treatment phase, or stage. However, only patients with Stage II-III disease from IRB #05015 will be accrued, in order to assure that sufficient tumor tissue will be available.

Inclusion Criteria:

  • Female,
  • Breast Cancer
  • > 18 years,
  • regardless of histology, treatment phase, or stage

Exclusion Criteria:

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01231386

Contact: George Somlo, MD 800 826-4673 gsomlo@coh.org

United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Michele Kirschenbaum    800-826-4673    mkirschenbaum@coh.org   
Contact: Suzanne Swain-Cabriales, RN    800 826-4673    sswain-cabriales@coh.org   
Principal Investigator: George Somlo, MD         
Sponsors and Collaborators
City of Hope Medical Center
Principal Investigator: George Somlo, MD City of Hope Medical Center
More Information

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT01231386     History of Changes
Other Study ID Numbers: 09147
First Posted: November 1, 2010    Key Record Dates
Last Update Posted: August 22, 2017
Last Verified: August 2017

Keywords provided by City of Hope Medical Center:
Female Breast Cancer
miRNA expression
Neoadjuvant/Adjuvant Treatment
Locally and Inflammatory Breast Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Inflammatory Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases