Informative Tools to Optimize Neoadjuvant Therapy in ER Positive, HER2 Negative Breast Cancers (ER)
Primary Purpose
Breast Cancer
Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Intervention 1
Intervention 2
Sponsored by
About this trial
This is an interventional diagnostic trial for Breast Cancer
Eligibility Criteria
Inclusion Criteria:
- Patient must be between the ages (inclusive) of 18-89.
- Patient has adequate performance status (PS ECOG 0,1 or Karnofsky performance status ≥70) and is a medically fit candidate for treatment of their cancer with systemic chemotherapy and/or hormonal therapy with no contra-indications to both systemic therapy options.
- Patient is medically fit enough to be a surgical candidate.
- Patient must be able to give informed consent directly or through the assistance of an interpreter.
- Pathological confirmation of breast cancer by core biopsy.
- Ductal or lobular breast cancer.
- Breast cancer with a primary tumour (clinically selected T2-T4) OR clinically node positive.
- Breast cancer is clinically palpable either in the breast, axilla or other nodal site.
- ER positive by IHC (Allred >=4).
- Her2Neu negative by IHC (0 or 1+) or FISH by current ASCO/CAP guidelines.
Exclusion Criteria:
- Patient is a male with breast cancer.
- Patients have ER negative tumors (ER-) by local or central BCCA assessment.
- Patients have HER2 positive tumors by local or central BCCA assessment.
- Patients have known metastatic breast cancer or develop metastatic disease prior to surgery.
- Patients are unable to give consent or understand written language.
- Patients with poor performance status (ECOG 2-4) in whom consideration of neoadjuvant chemotherapy OR hormonal therapy would be contraindicated.
- Patients who are not fit enough to be a surgical candidate.
- Pregnant women in whom consideration of neoadjuvant chemotherapy or neoadjuvant hormonal therapy would be contraindicated.
- Patients who receive less than 2 weeks of neoadjuvant systemic therapy.
- Patients who have not undergone surgical resection 12 months after enrollment.
For intervention 1 only:
- Patients with tumors that on GHI central pathological review appears inadequate for the Oncotype DX® assay.
- Patients with tumors that on BCCA pathological review appears inadequate for Ki-67 immunohistochemistry.
For intervention 2 only:
1. Patients with a pacemaker or contra-indication to MRI.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Eligible patients
Arm Description
Outcomes
Primary Outcome Measures
Feasibility of neoajduvant Ki-67 and Oncotype DX, defined as >=75% enrollment rate for all screened patients
• Technical feasibility of obtaining Ki-67 and Oncotype DX assay from a core biopsy sample in >= 75% of samples tested, prior to the initiation of systemic treatment.
Turnaround time of Ki-67 and Oncotype DX, defined as time from patient consent to date results are obtained
Turnaround time will be defined as:
Time from patient consent to reporting of the Ki-67 and Oncotype DX
Feasibility of MRI prior to neoadjuvant systemic treatment, defined as >=75% of patients who receive an MRI before the start of neoadjuvant treatment
• Practical feasibility of obtaining serial MRIs with the existing means, resources and booking circumstances in >=75% of cases prior to the initiation of systemic therapy and surgical resection
Turnaround time of MRI prior to neoadjuvant systemic treatment, defined as time from patient consent to date of 1st MRI
Turnaround time will be defined as:
• Time from patient consent to pre-treatment (baseline) MRI
Secondary Outcome Measures
Correlation of Ki-67 and Oncotype DX to each other and to the outcome of neoadjuvant systemic treatment.
To characterize how the results of the Ki-67 Oncotype DX assay relate to the outcome of neoadjuvant systemic treatment and whether the results correlate to each other (Ki-67 and Oncotype DX).
Predictive association of Ki-67 and Oncotype to invasive locoregional or systemic relapse
• Time from study enrollment to the development of invasive locoregional or systemic breast cancer.
Predictive association of Ki-67 and Oncotype to overall survival
• Time from enrollment to death from any cause.
Impact of serial MRI on changes to surgical planning
Changes from original to final surgical plan.
Correlation of serial MRI to clinical and pathological response
Characterize how the results of serial MRIs affect surgical planning and how the radiological response relates to clinical response and pathological response.
Patient reported outcomes assessed by questionnaire
Patient reported outcomes assessed with a questionnaire exploring decisional conflict.
9 questions are asked of patients regarding the MRI results and its impact on decision making. The scale is a 5 point scale, ranging from strongly disagree (1) to strongly agree (5). Results will be reported qualitatively.
Full Information
NCT ID
NCT03790813
First Posted
November 30, 2018
Last Updated
December 28, 2018
Sponsor
British Columbia Cancer Agency
Collaborators
Genomic Health®, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03790813
Brief Title
Informative Tools to Optimize Neoadjuvant Therapy in ER Positive, HER2 Negative Breast Cancers
Acronym
ER
Official Title
Informative Tools to Optimize Neoadjuvant Therapy in ER Positive, HER2 Negative Breast Cancers
Study Type
Interventional
2. Study Status
Record Verification Date
December 2018
Overall Recruitment Status
Not yet recruiting
Study Start Date
January 7, 2019 (Anticipated)
Primary Completion Date
December 31, 2019 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
British Columbia Cancer Agency
Collaborators
Genomic Health®, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study evaluates the addition of Ki-67, Oncotype DX and MRI in the treatment of early stage breast cancer with neoadjuvant treatment. All enrolled patients will have Ki-67 and Oncotype AND/OR an MRI before and after surgery.
Detailed Description
Based on what is known about the treatment of breast cancer, there are occasional advantages to giving treatment before surgery. Some of these advantages can include shrinking a large breast cancer to facilitate surgery, shrinking a breast cancer to allow breast conservation (avoid a mastectomy), and evaluating how effective a treatment is in real-time, based on its effect on the breast cancer.
When recommending treatment with hormone therapy and/or chemotherapy, doctors take into consideration all the characteristics of a breast cancer. Over recent years, is has been recognized that additional tests can help predict the behavior of a cancer and predict the possible benefit of hormone therapy and/or chemotherapy. Because there is no way to identify exactly who benefits from chemotherapy, many patients receive chemotherapy when they might not need it.
This study involves the use of 2 separate tests. The first is called Ki-67 and is done using a piece of tumour that is taken during a needle biopsy. The second, called the Oncotype DX, is made by Genomic Health, Inc, located in Redwood, CA, USA. This test also uses a piece of tumour that was retrieved during a needle biopsy. The pieces will be tested in a specialized laboratory that can measure the levels of a specific set of genes in the tumour. The laboratory that performs this test (Redwood, CA, USA) has been certified by federal and state agencies in the United States to perform the test (called Oncotype DX). The results of the test are turned into a score (called Recurrence Score) that has been used for patients receiving treatment after surgery, but has not yet been used when treatment is given before surgery.
The standard practice for this type of cancer is for the patient and their doctor to decide whether they should receive chemotherapy in addition to hormone therapy or to take hormone therapy alone, prior to surgery. The Ki-67 is inconsistently used in British Columbia prior to surgery, but may be used routinely in other centers. Usually, the Oncotype DX test is not available to aid in this decision outside of a research study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Eligible patients
Arm Type
Experimental
Intervention Type
Diagnostic Test
Intervention Name(s)
Intervention 1
Intervention Description
Ki-67 and Oncotype DX® will be performed on the baseline core biopsy specimen prior to initiation of neoadjuvant systemic therapy.
Intervention Type
Diagnostic Test
Intervention Name(s)
Intervention 2
Intervention Description
MRI will be performed prior to initiation of neoadjuvant systemic therapy and at the end of treatment.
Primary Outcome Measure Information:
Title
Feasibility of neoajduvant Ki-67 and Oncotype DX, defined as >=75% enrollment rate for all screened patients
Description
• Technical feasibility of obtaining Ki-67 and Oncotype DX assay from a core biopsy sample in >= 75% of samples tested, prior to the initiation of systemic treatment.
Time Frame
1 month
Title
Turnaround time of Ki-67 and Oncotype DX, defined as time from patient consent to date results are obtained
Description
Turnaround time will be defined as:
Time from patient consent to reporting of the Ki-67 and Oncotype DX
Time Frame
1 month
Title
Feasibility of MRI prior to neoadjuvant systemic treatment, defined as >=75% of patients who receive an MRI before the start of neoadjuvant treatment
Description
• Practical feasibility of obtaining serial MRIs with the existing means, resources and booking circumstances in >=75% of cases prior to the initiation of systemic therapy and surgical resection
Time Frame
6 months
Title
Turnaround time of MRI prior to neoadjuvant systemic treatment, defined as time from patient consent to date of 1st MRI
Description
Turnaround time will be defined as:
• Time from patient consent to pre-treatment (baseline) MRI
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Correlation of Ki-67 and Oncotype DX to each other and to the outcome of neoadjuvant systemic treatment.
Description
To characterize how the results of the Ki-67 Oncotype DX assay relate to the outcome of neoadjuvant systemic treatment and whether the results correlate to each other (Ki-67 and Oncotype DX).
Time Frame
6 months
Title
Predictive association of Ki-67 and Oncotype to invasive locoregional or systemic relapse
Description
• Time from study enrollment to the development of invasive locoregional or systemic breast cancer.
Time Frame
5 years
Title
Predictive association of Ki-67 and Oncotype to overall survival
Description
• Time from enrollment to death from any cause.
Time Frame
5 years
Title
Impact of serial MRI on changes to surgical planning
Description
Changes from original to final surgical plan.
Time Frame
6 months
Title
Correlation of serial MRI to clinical and pathological response
Description
Characterize how the results of serial MRIs affect surgical planning and how the radiological response relates to clinical response and pathological response.
Time Frame
6 months
Title
Patient reported outcomes assessed by questionnaire
Description
Patient reported outcomes assessed with a questionnaire exploring decisional conflict.
9 questions are asked of patients regarding the MRI results and its impact on decision making. The scale is a 5 point scale, ranging from strongly disagree (1) to strongly agree (5). Results will be reported qualitatively.
Time Frame
6 months
10. Eligibility
Sex
Female
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
89 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patient must be between the ages (inclusive) of 18-89.
Patient has adequate performance status (PS ECOG 0,1 or Karnofsky performance status ≥70) and is a medically fit candidate for treatment of their cancer with systemic chemotherapy and/or hormonal therapy with no contra-indications to both systemic therapy options.
Patient is medically fit enough to be a surgical candidate.
Patient must be able to give informed consent directly or through the assistance of an interpreter.
Pathological confirmation of breast cancer by core biopsy.
Ductal or lobular breast cancer.
Breast cancer with a primary tumour (clinically selected T2-T4) OR clinically node positive.
Breast cancer is clinically palpable either in the breast, axilla or other nodal site.
ER positive by IHC (Allred >=4).
Her2Neu negative by IHC (0 or 1+) or FISH by current ASCO/CAP guidelines.
Exclusion Criteria:
Patient is a male with breast cancer.
Patients have ER negative tumors (ER-) by local or central BCCA assessment.
Patients have HER2 positive tumors by local or central BCCA assessment.
Patients have known metastatic breast cancer or develop metastatic disease prior to surgery.
Patients are unable to give consent or understand written language.
Patients with poor performance status (ECOG 2-4) in whom consideration of neoadjuvant chemotherapy OR hormonal therapy would be contraindicated.
Patients who are not fit enough to be a surgical candidate.
Pregnant women in whom consideration of neoadjuvant chemotherapy or neoadjuvant hormonal therapy would be contraindicated.
Patients who receive less than 2 weeks of neoadjuvant systemic therapy.
Patients who have not undergone surgical resection 12 months after enrollment.
For intervention 1 only:
Patients with tumors that on GHI central pathological review appears inadequate for the Oncotype DX® assay.
Patients with tumors that on BCCA pathological review appears inadequate for Ki-67 immunohistochemistry.
For intervention 2 only:
1. Patients with a pacemaker or contra-indication to MRI.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nathalie LeVasseur, MD
Phone
604-877-6000x2734
Email
nathalie.levasseur@bccancer.bc.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephen Chia, MD
Organizational Affiliation
BCCA
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Informative Tools to Optimize Neoadjuvant Therapy in ER Positive, HER2 Negative Breast Cancers
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