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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by City of Hope Medical Center
Sponsor:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT01231386
First received: October 27, 2010
Last updated: October 2, 2014
Last verified: October 2014

October 27, 2010
October 2, 2014
April 2010
October 2016   (final data collection date for primary outcome measure)
  • Performance of miRNA profiling from tumor samples from primary breast tumors [ Time Frame: 3 years after completion of sample collection ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Determination of specific miRNA functions [ Time Frame: 3 years after completion of sample collection ] [ Designated as safety issue: No ]
  • Determination of ability to knock down functionally relevant overexpressed miRNAs by miR-sponge/antagomirs [ Time Frame: 3 years after completion of sample collection ] [ Designated as safety issue: No ]
  • Design of prospective pilot phase I-II trials to interfere with dysfunctional/dysregulated miRNA expression [ Time Frame: 3 years after completion of sample collection ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01231386 on ClinicalTrials.gov Archive Site
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MIRNA Profiling of Breast Cancer in Patients Undergoing Neoadjuvant or Adjuvant Treatment for Locally Advanced & Inflammatory Breast Cancer
MIRNA Profiling of Breast Cancer in Patients Undergoing Neoadjuvant or Adjuvant Treatment for Locally Advanced & Inflammatory Breast Cancer

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.

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

Observational
Observational Model: Cohort
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Retention:   Samples With DNA
Description:

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.

Probability Sample

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.

Breast Cancer
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
165
Not Provided
October 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

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

Exclusion Criteria:

-

Female
18 Years and older
No
Contact: George Somlo, MD 800 826-4673 gsomlo@coh.org
United States
 
NCT01231386
09147
Yes
City of Hope Medical Center
City of Hope Medical Center
Not Provided
Principal Investigator: George Somlo, MD City of Hope Medical Center
City of Hope Medical Center
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP