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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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ClinicalTrials.gov Identifier: NCT04928261
Recruitment Status : Recruiting
First Posted : June 16, 2021
Last Update Posted : May 2, 2022
Sponsor:
Information provided by (Responsible Party):
Ottawa Hospital Research Institute

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.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Trastuzumab Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : December 13, 2021
Estimated Primary Completion Date : September 2023
Estimated Study Completion Date : September 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Trastuzumab

Arm Intervention/treatment
Experimental: De-escalated HER2 targeted treatment
Patients with early-stage HER2-positive breast cancer who demonstrate a pathological complete response at time of surgery.
Drug: Trastuzumab
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.
Other Name: Herceptin




Primary Outcome Measures :
  1. Multiple site activation [ Time Frame: 1 year after first participant is accrued ]
    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.

  2. Medical oncologist active participation [ Time Frame: Through to end of accrual - average 2 years ]
    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.

  3. 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 ]
    Enrolment of at least 50 participants across all sites within 9 months of the fourth site accruing its first participant.


Secondary Outcome Measures :
  1. Cardiac events [ Time Frame: 3 years after study enrolment ]
    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

  2. Rate of HER2-positive treatment discontinuation [ Time Frame: 6 months after study enrolment ]
    De-escalated HER2-positive treatment discontinuation and the reasons why treatment was discontinued

  3. Health-related quality of life [ Time Frame: Baseline, 3, 6, 12 and 36 months after study enrolment ]
    Health-related quality of life measure using the EuroQol-5 Dimension-5 Level (EQ-5D-5L) questionnaire.

  4. Incremental cost-effectiveness ratios [ Time Frame: 3 years from study enrolment ]
    The difference in cost between 6 months of HER2-positive therapy versus the standard 12 months of HER2-positive therapy.

  5. Disease free survival [ Time Frame: 3 years from study enrolment ]
    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

  6. Overall survival [ Time Frame: 3 years from study enrolment ]
    Overall Survival (OS), defined as the number of people alive, with or without signs of cancer at 3 years



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04928261


Contacts
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Contact: Lisa Vandermeer, MSc 6137377700 ext 73039 lvandermeer@toh.ca
Contact: Michelle Liu 613-737-7700 ext 79150 miliu@ohri.ca

Locations
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Canada, Ontario
The Ottawa Hospital Cancer Centre Recruiting
Ottawa, Ontario, Canada, K1H8M2
Contact: Lisa Vandermeer    6137377700 ext 73039    lvandermeer@ohri.ca   
Principal Investigator: Sharon McGee, MD         
Sponsors and Collaborators
Ottawa Hospital Research Institute
Investigators
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Principal Investigator: Sharon McGee, MD Ottawa Hospital Research Institute
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Responsible Party: Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier: NCT04928261    
Other Study ID Numbers: REaCT-HER TIME
First Posted: June 16, 2021    Key Record Dates
Last Update Posted: May 2, 2022
Last Verified: April 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ottawa Hospital Research Institute:
Cardiac toxicities
Her2 Positive
Pathological complete response
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Trastuzumab
Antineoplastic Agents, Immunological
Antineoplastic Agents