Clinical trial NCT04928261: 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
Overall status: RECRUITING
Phase: PHASE4
Conditions: Breast Cancer
Keywords: Cardiac toxicities
Her2 Positive
Pathological complete response
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
First posted: 2021-06-16
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Multiple site activation
timeFrame: 1 year after first participant is accrued
measure: Medical oncologist active participation
timeFrame: Through to end of accrual - average 2 years
measure: Enrolment of at least 50 participants across all sites within 9 months of the fourth site accruing its first participant
timeFrame: 9 months after fourth site accrues first participant
Secondary outcomes:
measure: Cardiac events
timeFrame: 3 years after study enrolment
measure: Rate of HER2-positive treatment discontinuation
timeFrame: 6 months after study enrolment
measure: Health-related quality of life
timeFrame: Baseline, 3, 6, 12 and 36 months after study enrolment
measure: Incremental cost-effectiveness ratios
timeFrame: 3 years from study enrolment
measure: Disease free survival
timeFrame: 3 years from study enrolment
measure: Overall survival
timeFrame: 3 years from study enrolment
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre
state: Ontario
Study officials:
affiliation: Ottawa Hospital Research Institute
name: Sharon McGee, MD
role: PRINCIPAL_INVESTIGATOR
References: