Circulating miRNAs. ICORG 10-11, V2

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01722851
Recruitment Status : Recruiting
First Posted : November 7, 2012
Last Update Posted : August 10, 2017
Information provided by (Responsible Party):
Cancer Trials Ireland

October 24, 2012
November 7, 2012
August 10, 2017
May 2011
December 2017   (Final data collection date for primary outcome measure)
  • Relationship between changes in a patients circulating miRNA expression levels over the course of their systemic therapy, and their response to that treatment. [ Time Frame: up to week 66-92 ]
    Patients' response to treatment will be determined using 3 standard parameters: clinical, radiological and pathological responses.
  • Correlation of systemic miRNA levels with standard biomarkers of response [ Time Frame: up to week 66-92 ]
    Standard bio markers of response include serum CEA and Ca15-3 levels
Same as current
Complete list of historical versions of study NCT01722851 on Archive Site
  • Relationship between circulating miRNA profiles and patients' intrinsic subtype of breast cancer [ Time Frame: up to week 66-92 ]
  • Relationship between miRNA expression levels and other existing clinicopathological parameters. [ Time Frame: up to week 66-92 ]
    Other existing clinicopathological parameters include: ER, PR and HER2 status, stage of disease,histological grade and size of the tumour, and the Nottingham Prognostic Index.
Same as current
Not Provided
Not Provided
Circulating miRNAs. ICORG 10-11, V2
Circulating miRNAs: Novel Breast Cancer Biomarkers and Their Use for Guiding and Monitoring Response to Chemotherapy
To identify a panel of circulating miRNA markers which could help identify those breast cancer patients who are most likely to respond well to neoadjuvant and adjuvant chemotherapy, and indeed serve as an overall prognostic factor and stratify patients into risk categories which would further guide their management. Similarly, the investigators aim to identify a panel of circulating miRNA markers which could monitor patient's response to chemotherapy and hormonal therapies. Ideally a suitable panel of markers would show significant changes in expression level in good-responders whilst little or no change would be observed in miRNA expression in non-responders.

Primary Objectives:

  1. To identify a panel of miRNAs, detectable in the circulation, which are altered in breast cancer patients
  2. To identify specific combinations of miRNAs ('signatures') which associate with breast cancer intrinsic subtypes, and thereby could aid in prognostication and treatment planning on an individual patient basis.

Secondary Objective:

1. To determine if systemic miRNA analysis can be used as a biomarker for monitoring response to chemotherapy, in the neoadjuvant setting and in patients who present with breast cancer recurrence and are treated with upfront chemotherapy

This is a prospective cohort studies, involving two study cohorts:

Cohort 1: Newly diagnosed breast cancer patients, Cohort 2: Recurrent breast cancer patients

Blood Sampling:

  • 1st (baseline) blood sample at presentation before commencing neoadjuvant (cohort 1) or systemic (cohort 2) treatment.
  • 2nd blood sample midway through their chemotherapy treatment (after 2nd cycle if they are enrolled in a 4 cycle regimen, or after 4th cycle if they are prescribed an 8 week regimen).
  • 3rd blood sample post-chemotherapy and before surgery (if applicable).
  • 4th blood sample 2-4 weeks after surgery, or after last blood sampling if surgery is not envisaged
  • 5th blood sample 12-18 month after surgery or after 3rd blood sampling if surgery is not envisaged.

GUH only: Tissue samples will be taken at time of biopsy and/or at time of surgery.

All samples will be processed for miRNA quantification - a panel of 9 cancer-specific miRNAs will be measured in each sample, and the change in each patient's miRNA expression levels monitored over the course of their treatment.

Blood samples will be processed for miRNA analysis, which involves:

  1. Lysis using Trizol
  2. RNA isolation
  3. Assessing concentration and integrity of RNA using Nanodrop spectrophotometry
  4. cDNA synthesis (using miRNA specific stem loop primers)
  5. PCR amplification and relative quantification (using miRNA specific probes)
Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Not Provided
Non-Probability Sample

Investigators aim to study two populations of breast cancer patients:

  1. Patients undergoing neoadjuvant chemotherapy for breast cancer at tertiary referral breast cancer centres in Ireland.

    For GUH only: Additionally,investigators wish to evaluate miRNA expression levels in patients' diagnostic core biopsies.

  2. Investigators also wish to study the same panel of miRNAs in patients who present with disease recurrence or disease progression, and who are commenced on systemic therapies (hormonal and/or chemotherapy).
  • Breast Cancer
  • Newly Diagnosed Breast Cancer
  • Recurrent Breast Cancer
Not Provided
  • Newly diagnosed breast cancer patients
    All newly diagnosed breast cancer patients who are scheduled to undergo neoadjuvant chemotherapy will be recruited and enrolled into this study at the time of diagnosis, pending gaining informed consent.
  • Recurrent breast cancer patients
    All patients with a history of breast cancer who represent with disease recurrence or progression, and are commencing up-front hormonal therapy or chemotherapy, will also be recruited and enrolled.
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Same as current
Not Provided
December 2017   (Final data collection date for primary outcome measure)

Inclusion Criteria:

Patients must satisfy the following criteria:

  1. All patients with a new diagnosis of breast cancer, who are destined to undergo neoadjuvant chemotherapy.
  2. Patients with breast cancer recurrence or disease progression who will receive up-front chemotherapy.
  3. Patients must be aged 18 years or over.
  4. Patients must be able to give written informed consent.

Exclusion Criteria:

1. Patients who do not fulfil the inclusion criteria mentioned above

Sexes Eligible for Study: Female
18 Years and older   (Adult, Older Adult)
ICORG 10-11
Not Provided
Not Provided
Not Provided
Cancer Trials Ireland
Cancer Trials Ireland
Not Provided
Not Provided
Cancer Trials Ireland
August 2017