Evaluating 6-months of HER2-targeted Therapy in Patients With HER2 Positive Early-stage Breast Cancer That Achieve a Pathological Complete Response to Neoadjuvant Systemic Therapy
Primary Purpose
Breast Cancer
Status
Active
Phase
Phase 4
Locations
Canada
Study Type
Interventional
Intervention
Trastuzumab
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer focused on measuring Cardiac toxicities, Her2 Positive, Pathological complete response
Eligibility Criteria
Inclusion Criteria:
- Early-stage (I-III, i.e. non-metastatic) as per AJCC 8th edition, ER/PR positive or negative, HER2-positive as per 2018 American Society of Clinical Oncology/College of American Pathologists human epidermal growth factor receptor 2 (HER2) testing in breast cancer guidelines.
- Treated with neoadjuvant chemotherapy and HER2 targeted therapy preoperatively with a pathological complete response (pCR) defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy at surgery. Must have received less than 6 months of HER2 targeted therapy
- Able to provide verbal consent and complete questionnaires in English or French
Exclusion Criteria:
- Residual invasive disease following neoadjuvant therapy, or metastatic disease
- Contraindication to further HER2-targeted therapy following completion of neoadjuvant treatment
- Any psychological, familial, sociological or geographical condition potentially hampering compliance with the trial protocol
Sites / Locations
- The Ottawa Hospital Cancer Centre
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
De-escalated HER2 targeted treatment
Arm Description
Patients with early-stage HER2-positive breast cancer who demonstrate a pathological complete response at time of surgery.
Outcomes
Primary Outcome Measures
Multiple site activation
Evaluating the feasibility of multiple Canadian site activation within the first year of study accrual. Achieved by the activation of at least 4 Canadian sites within 1 year of the first patient being accrued into the study.
Medical oncologist active participation
Evaluating the number of medical oncologists at each study site who actively participate in the trial. Active participation includes approaching eligible patients for the study, as well as following up with the patients who are taking part in the study.
Enrolment of at least 50 participants across all sites within 9 months of the fourth site accruing its first participant
Enrolment of at least 50 participants across all sites within 9 months of the fourth site accruing its first participant.
Secondary Outcome Measures
Cardiac events
Cardiac events defined as death from a cardiac or heart failure of New York Heart Association (NYHA) class III or IV, or with a decrease in the left ventricular ejection fraction of at least 10 percentage points from baseline to a value of less than 50%. Cardiac monitoring will be assessed as per physician standards
Rate of HER2-positive treatment discontinuation
De-escalated HER2-positive treatment discontinuation and the reasons why treatment was discontinued
Health-related quality of life
Health-related quality of life measure using the EuroQol-5 Dimension-5 Level (EQ-5D-5L) questionnaire.
Incremental cost-effectiveness ratios
The difference in cost between 6 months of HER2-positive therapy versus the standard 12 months of HER2-positive therapy.
Disease free survival
Disease Free Survival (DFS), defined as the percentage of people in the trial who are alive and disease-free (no local invasive breast cancer recurrence, new local invasive breast cancer) at 3 years
Overall survival
Overall Survival (OS), defined as the number of people alive, with or without signs of cancer at 3 years
Full Information
NCT ID
NCT04928261
First Posted
May 4, 2021
Last Updated
March 1, 2023
Sponsor
Ottawa Hospital Research Institute
1. Study Identification
Unique Protocol Identification Number
NCT04928261
Brief Title
Evaluating 6-months of HER2-targeted Therapy in Patients With HER2 Positive Early-stage Breast Cancer That Achieve a Pathological Complete Response to Neoadjuvant Systemic Therapy
Official Title
A Single-arm, Multicentre, Pragmatic Trial Evaluating 6-months of HER2-targeted Therapy in Patients With HER2 Positive Early-stage Breast Cancer That Achieve a Pathological Complete Response to Neoadjuvant Systemic Therapy (REaCT-HER TIME)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 13, 2021 (Actual)
Primary Completion Date
September 2023 (Anticipated)
Study Completion Date
September 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ottawa Hospital Research Institute
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The activity of trastuzumab in early-stage, HER2-positive breast cancer, has been demonstrated in many studies, with meta-analyses showing that in combination with a variety of chemotherapy backbones, trastuzumab reduces the risk of recurrence by nearly half, and death by a third. However, treatment with trastuzumab can result in cardiotoxicity, including heart failure, as well as the significant cost of treatment and the requirement for patients to attend the chemotherapy unit for treatment every 3 weeks for one year. Therefore there has been increasing interest in identifying which patients can safely have less treatment. The investigators therefore propose a real-world, single arm, multicentre trial evaluating 6 months of HER2 targeted therapy, for patients with early-stage, HER2 positive breast cancer, who achieve a pathological complete response (pCR) with upfront systemic chemotherapy and HER2 targeted therapy.
Detailed Description
The activity of trastuzumab in early-stage, HER2-positive breast cancer, has been demonstrated in many studies, with meta-analyses showing that in combination with a variety of chemotherapy backbones, trastuzumab reduces the risk of recurrence by nearly half, and death by a third. However, treatment with trastuzumab can result in cardiotoxicity, including heart failure, as well as the significant cost of treatment and the requirement for patients to attend the chemotherapy unit for treatment every 3 weeks for one year. Therefore there has been increasing interest in identifying which patients can safely have less treatment. The duration of adjuvant trastuzumab in early-stage breast cancer in the majority of studies was empirically set at 12 months, which became the de facto standard of care. Neoadjuvant treatment has become the new standard of care for patients with early-stage HER2-positive disease. While patients with residual disease benefit from further alternative treatment those with a pathological complete response (pCR) have an excellent outcome and are candidates for treatment de-escalation. The investigators therefore propose a real-world, single arm, multicentre trial evaluating 6 months of HER2 targeted therapy, for patients with early-stage, HER2 positive breast cancer, who achieve a pCR with upfront systemic chemotherapy and HER2 targeted therapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
Cardiac toxicities, Her2 Positive, Pathological complete response
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
De-escalated HER2 targeted treatment
Arm Type
Experimental
Arm Description
Patients with early-stage HER2-positive breast cancer who demonstrate a pathological complete response at time of surgery.
Intervention Type
Drug
Intervention Name(s)
Trastuzumab
Other Intervention Name(s)
Herceptin
Intervention Description
Patients with early-stage HER2-positive breast cancer who demonstrate a pathological complete response at time of surgery will be treated with HER2 targeted therapy for a total of 9 treatments every 3 weeks (or its equivalent if given weekly) including the treatment received preoperatively.
Primary Outcome Measure Information:
Title
Multiple site activation
Description
Evaluating the feasibility of multiple Canadian site activation within the first year of study accrual. Achieved by the activation of at least 4 Canadian sites within 1 year of the first patient being accrued into the study.
Time Frame
1 year after first participant is accrued
Title
Medical oncologist active participation
Description
Evaluating the number of medical oncologists at each study site who actively participate in the trial. Active participation includes approaching eligible patients for the study, as well as following up with the patients who are taking part in the study.
Time Frame
Through to end of accrual - average 2 years
Title
Enrolment of at least 50 participants across all sites within 9 months of the fourth site accruing its first participant
Description
Enrolment of at least 50 participants across all sites within 9 months of the fourth site accruing its first participant.
Time Frame
9 months after fourth site accrues first participant
Secondary Outcome Measure Information:
Title
Cardiac events
Description
Cardiac events defined as death from a cardiac or heart failure of New York Heart Association (NYHA) class III or IV, or with a decrease in the left ventricular ejection fraction of at least 10 percentage points from baseline to a value of less than 50%. Cardiac monitoring will be assessed as per physician standards
Time Frame
3 years after study enrolment
Title
Rate of HER2-positive treatment discontinuation
Description
De-escalated HER2-positive treatment discontinuation and the reasons why treatment was discontinued
Time Frame
6 months after study enrolment
Title
Health-related quality of life
Description
Health-related quality of life measure using the EuroQol-5 Dimension-5 Level (EQ-5D-5L) questionnaire.
Time Frame
Baseline, 3, 6, 12 and 36 months after study enrolment
Title
Incremental cost-effectiveness ratios
Description
The difference in cost between 6 months of HER2-positive therapy versus the standard 12 months of HER2-positive therapy.
Time Frame
3 years from study enrolment
Title
Disease free survival
Description
Disease Free Survival (DFS), defined as the percentage of people in the trial who are alive and disease-free (no local invasive breast cancer recurrence, new local invasive breast cancer) at 3 years
Time Frame
3 years from study enrolment
Title
Overall survival
Description
Overall Survival (OS), defined as the number of people alive, with or without signs of cancer at 3 years
Time Frame
3 years from study enrolment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Early-stage (I-III, i.e. non-metastatic) as per AJCC 8th edition, ER/PR positive or negative, HER2-positive as per 2018 American Society of Clinical Oncology/College of American Pathologists human epidermal growth factor receptor 2 (HER2) testing in breast cancer guidelines.
Treated with neoadjuvant chemotherapy and HER2 targeted therapy preoperatively with a pathological complete response (pCR) defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy at surgery. Must have received less than 6 months of HER2 targeted therapy
Able to provide verbal consent and complete questionnaires in English or French
Exclusion Criteria:
Residual invasive disease following neoadjuvant therapy, or metastatic disease
Contraindication to further HER2-targeted therapy following completion of neoadjuvant treatment
Any psychological, familial, sociological or geographical condition potentially hampering compliance with the trial protocol
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sharon McGee, MD
Organizational Affiliation
Ottawa Hospital Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Ottawa Hospital Cancer Centre
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H8M2
Country
Canada
12. IPD Sharing Statement
Learn more about this trial
Evaluating 6-months of HER2-targeted Therapy in Patients With HER2 Positive Early-stage Breast Cancer That Achieve a Pathological Complete Response to Neoadjuvant Systemic Therapy
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