Circulating miRNAs.

Breast Cancer Clinical Trial

Official title:

Novel Breast Cancer Biomarkers and Their Use for Guiding and Monitoring Response to Chemotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01722851
• Other study ID #: ICORG 10-11
• Status: Completed
• Start date: May 2011
• Est. completion date: December 2021

Study information

• Verified date: April 2023
• Source: Cancer Trials Ireland
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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 and/or hormonal therapy.

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

Cohort 1: All newly diagnosed breast cancer patients who are scheduled to undergo neoadjuvant chemotherapy.

Cohort 2: All breast cancer patients who present with metastatic disease, disease recurrence or progression, who are commencing up-front chemotherapy +/- hormonal therapy.

Cohort 3: All breast cancer patients who present with metastatic disease who are commencing hormonal therapy only.

Blood Sample

Blood Sampling - Cohort 1:

• Blood sample 1: at presentation before commencing neoadjuvant treatment.

• Blood sample 2: 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).

• Blood sample 3: post-chemotherapy (before surgery as applicable).

• Blood sample 4: 2 to 4 weeks after surgery, or 2 to 4 weeks post 3rd blood sampling if patients do not undergo surgery.

• Blood sample 5: once during follow-up of 12 to 18 months after surgery or 12 to 18 months post 3rd blood sampling if patients do not undergo surgery.

Blood Sampling - Cohort 2:

• Pre-treatment blood sample: at presentation before commencing treatment.

• On study blood samples: taken at monthly (± 1 week) intervals for a period of 6 months from date of pre-treatment blood sample, despite whether the patient is on treatment or completed treatment.

On study blood sample 1: 1 month (± 1 week) from date of pre-treatment blood sample

On study blood sample 2: 2 months (± 1 week) from date of pre- treatment blood sample

On study blood sample 3: 3 months (± 1 week) from date of pre-treatment blood sample

On study blood sample 4: 4 months (± 1 week) from date of pre-treatment blood sample

On study blood sample 5: 5 months (± 1 week) from date of pre-treatment blood sample

On study blood sample 6: 6 months (± 1 week) from date of pre-treatment blood sample

• End of study blood sample: once during follow-up of 12 to 18 months from date of pre-treatment blood sample or at the time of disease progression.

Blood Sampling - Cohort 3:

• Pre-treatment blood sample: at presentation before commencing treatment.

• On study blood samples: taken at the following time points despite whether the patient is on treatment or completed treatment.

On study blood sample 1: 3 months (± 2 weeks) from date of pre-treatment blood sample On study blood sample 2: 6 months (± 2 weeks) from date of pre-treatment blood sample On study blood sample 3: 12 months (± 2 weeks) from date of pre-treatment blood sample

• End of study blood sample: 18 months (± 2 weeks) from date of pre-treatment blood sample or at the time of disease progression.

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 255
• Est. completion date: December 2021
• Est. primary completion date: April 1, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

1. Patient must meet the criteria for either:

Cohort 1: All patients with a new diagnosis of breast cancer, who are destined to undergo neoadjuvant chemotherapy.

OR Cohort 2: All breast cancer patients who present with metastatic disease, disease recurrence or progression who will receive up-front chemotherapy ± hormonal therapy.

OR Cohort 3: All breast cancer patient who present with metastatic disease who are commencing hormonal therapy only.

2. Patients must be aged 18 years or over.

3. Patients must be able to give written informed consent.

Exclusion Criteria

All patients, who do not fulfil the inclusion criteria mentioned above.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Newly Diagnosed Breast Cancer
• Recurrent Breast Cancer

Locations

Country	Name	City	State
Ireland	Bon Secours Hospital	Cork
Ireland	Beaumont Hospital	Dublin
Ireland	St James's Hospital	Dublin
Ireland	University Hospital Galway	Galway
Ireland	Letterkenny General Hospital	Letterkenny
Ireland	Sligo General Hospital	Sligo
Ireland	Midlands Regional Hospital Tullamore	Tullamore

Sponsors (1)

Lead Sponsor	Collaborator
Cancer Trials Ireland

Country where clinical trial is conducted

Ireland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relationship between changes in a patients circulating miRNA expression levels over the course of their systemic therapy, and their response to that treatment.	For cohort 1, a patient's response to treatment will be determined using 3 standard parameters: clinical, radiological and pathological responses.; For cohort 2 and 3, a patient's response to treatment will be evaluated using RECIST criteria version 1.1." For cohort 1, a patient's response to treatment will be determined using 3 standard parameters: clinical, radiological and pathological responses.; For cohort 2 and 3, a patient's response to treatment will be evaluated using RECIST criteria version 1.1."	Up to week 66-92
Primary	Correlation of systemic miRNA levels with standard biomarkers of response	Standard bio markers of response include serum CEA and Ca15-3 levels	Up to week 66-92
Secondary	Relationship between circulating miRNA profiles and patients' intrinsic subtype of breast cancer		Up to week 66-92
Secondary	Relationship between miRNA expression levels and other existing clinicopathological parameters.	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.	Up to week 66-92