A Phase II Trial of Preoperative HER2 Targeting and Endocrine Therapy in Postmenopausal Women With HER2 and HR Positive Breast Cancer
Trial Snapshot
- Phase
- Phase 2
- Sponsor
- Gangnam Severance Hospital
- Enrollment
- 132
- Locations
- 14
- Primary Endpoint
- The rate of pathologic complete response
Study Overview
Brief Summary
The purpose of this study is to evaluate whether trastuzumab and letrozole are effective and safe in the preoperative treatment for postmenopausal patients with hormone receptor-positive and HER2-positive breast cancer.
Detailed Description
Eligibility criteria
-
Ages Eligible for Study: ≥ 20 years
-
Invasive cancer (clinical stage IB-IIIB)
-
Measurable tumor larger than 1cm
-
ECOG status 0 or 1
-
Postmenopausal women
-
Age ≥55 years and amenorrhea
-
Age <55 years and amenorrhea for ≥12 months with FSH >30 mIU/ml
-
HER2 positive tumor
-
3 positive on IHC
-
2 positive on IHC with HER2 gene amplification on FISH or SISH using a single-probe or dual-probe
-
Estrogen receptor positive tumor
-
Positive ER expression with Allred score more than PS3/TS8 or modified Allred score more than PS4/TS7
-
Eligible cardiac function
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Invasive cancer (clinical stage IB-IIIC)
- •Measurable tumor larger than 1cm
- •ECOG status 0 or 1
- •Postmenopausal women
- •Age ≥55 years and amenorrhea
- •Age <55 years and amenorrhea for ≥12 months with FSH >30 mIU/ml
- •HER2 positive tumor
- •3 positive on IHC
- •2 positive on IHC with HER2 gene amplification on FISH or SISH using a single-probe or dual-probe
- •Estrogen receptor positive tumor
- •Positive ER expression with Allred score more than PS3/TS8 or modified Allred score more than PS4/TS7
- •Eligible cardiac function
- •Normal heard evaluated by ECG
- •Consider clinically non-significant arrythmia and ischemic change as normal
- •LVEF ≥ 55% measured by ECHO or MUGA scan
Exclusion Criteria
- •Inflammatory breast cancer
- •Bilateral breast cancer
- •Patients with previous breast cancer history
- •Patients with previous breast cancer treatment: Generally include hormone therapy, chemotherapy, and radiotherapy)
- •Patients having uncontrolled heart problems
- •Ischemic heart disease within 6 months
- •Congestive heart failure more than NYHA class II
- •Unstable angina
- •Clinically significant pericarditis
- •Amyloid heart disease
Arms & Interventions
Trastuzumab and Letrozole
- Concurrently initiate two drugs on Day 1 of Cycle 1
Intervention: Trastuzumab (Drug)
Trastuzumab and Letrozole
- Concurrently initiate two drugs on Day 1 of Cycle 1
Intervention: Letrozole (Drug)
Outcomes
Primary Outcomes
The rate of pathologic complete response
Time Frame: At time of surgery
No residual invasive cancer in breast regardless of axilla
Secondary Outcomes
- Safety profiles for the preoperative use of concurrent trastuzumab and letrozole(Up to 3 months after surgery)
- The rate of breast conservative surgery(Up to 3 weeks after surgery)
- Clinical Response Rate(At time of surgery)
- Total pathologic complete response (tpCR)(At time of surgery)
- Analysis of biomarkers based on baseline specimen and residual tumor(Baseline and at time of surgery)
- Association between clinical response rate and circulating tumor cells (CTCs)(Baseline and at time of surgery)
Investigators
Joon Jeong
Professor
Gangnam Severance Hospital