Circulating miRNAs. ICORG 10-11, V2

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by ICORG- All Ireland Cooperative Oncology Research Group
Sponsor:
Information provided by (Responsible Party):
ICORG- All Ireland Cooperative Oncology Research Group
ClinicalTrials.gov Identifier:
NCT01722851
First received: October 24, 2012
Last updated: August 11, 2014
Last verified: August 2014
  Purpose

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.


Condition
Breast Cancer
Newly Diagnosed Breast Cancer
Recurrent Breast Cancer

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Circulating miRNAs: Novel Breast Cancer Biomarkers and Their Use for Guiding and Monitoring Response to Chemotherapy

Resource links provided by NLM:


Further study details as provided by ICORG- All Ireland Cooperative Oncology Research Group:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Standard bio markers of response include serum CEA and Ca15-3 levels


Secondary Outcome Measures:
  • Relationship between circulating miRNA profiles and patients' intrinsic subtype of breast cancer [ Time Frame: up to week 66-92 ] [ Designated as safety issue: No ]
  • Relationship between miRNA expression levels and other existing clinicopathological parameters. [ Time Frame: up to week 66-92 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 122
Study Start Date: May 2011
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Groups/Cohorts
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.

Detailed Description:

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)
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

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).
Criteria

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01722851

Locations
Ireland
Beaumont Hospital Recruiting
Dublin, Ireland
Contact: Contact Person    01-8093760      
Principal Investigator: Arnold Hill, Prof         
St James's Hospital Recruiting
Dublin, Ireland
Contact: Contact person    01 410 3000      
Principal Investigator: John Kennedy, Dr         
University Hospital Galway Recruiting
Galway, Ireland
Contact: Contact Person    (0)91 524222      
Principal Investigator: Michael J Kerin, Prof         
Letterkenny General Hospital Recruiting
Letterkenny, Ireland
Contact: Contact Person    074-9123798      
Principal Investigator: Karen Duffy, Dr         
Sligo General Hospital Recruiting
Sligo, Ireland
Contact: Contact Person    (071) 9171111      
Principal Investigator: Michael Martin, Dr         
Sponsors and Collaborators
ICORG- All Ireland Cooperative Oncology Research Group
  More Information

No publications provided

Responsible Party: ICORG- All Ireland Cooperative Oncology Research Group
ClinicalTrials.gov Identifier: NCT01722851     History of Changes
Other Study ID Numbers: ICORG 10-11
Study First Received: October 24, 2012
Last Updated: August 11, 2014
Health Authority: Ireland: Health Information and Quality Authority

Keywords provided by ICORG- All Ireland Cooperative Oncology Research Group:
Breast Cancer
miRNAs
Newly diagnosed
Recurrent

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

ClinicalTrials.gov processed this record on October 23, 2014