Description:
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.
Title
- Brief Title: Neoadjuvant Trastuzumab and Letrozole for Postmenopausal Women
- Official Title: A Phase II Trial of Preoperative HER2 Targeting and Endocrine Therapy in Postmenopausal Women With HER2 and HR Positive Breast Cancer
Clinical Trial IDs
- ORG STUDY ID:
HERAKLES
- NCT ID:
NCT02214004
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Trastuzumab | Herceptin | Trastuzumab and Letrozole |
| Letrozole | Femara | Trastuzumab and Letrozole |
Purpose
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
- Normal heard evaluated by ECG
- Consider clinically non-significant arrythmia and ischemic change as normal
- LVEF ≥ 55% measured by ECHO or MUGA scan
Outcome measures
- Primary End-point
- The rate of pathologic complete response (pCR)
- No residual invasive cancer in breast
- Secondary End-point
- Clinical Response Rate
- Safety profiles for the preoperative use of concurrent trastuzumab and letrozole
- The rate of breast conservative surgery
- Total pathologic complete response (tpCR)
- No residual invasive cancer in breast and ipsilateral axilla
- Analysis of biomarkers based on baseline specimen and residual tumor
- Ki67 expression
- cDNA microarray: gene expression profiling
- Association between clinical response rate and circulating tumor cells (CTCs)
- CTCs are measured by CytoGen (SEOUL, KOREA)"
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Trastuzumab and Letrozole | Experimental | - Concurrently initiate two drugs on Day 1 of Cycle 1 | |
Eligibility Criteria
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | Female |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | The rate of pathologic complete response |
| Time Frame: | At time of surgery |
| Safety Issue: | |
| Description: | No residual invasive cancer in breast regardless of axilla |
Secondary Outcome Measures
| Measure: | Clinical Response Rate |
| Time Frame: | At time of surgery |
| Safety Issue: | |
| Description: | Clinical response includes complete response, partial response and stable disease. |
| Measure: | Safety profiles for the preoperative use of concurrent trastuzumab and letrozole |
| Time Frame: | Up to 3 months after surgery |
| Safety Issue: | |
| Description: | Toxicity according to CTCAE protocol from the initiated day to 3 months after surgery |
| Measure: | The rate of breast conservative surgery |
| Time Frame: | Up to 3 weeks after surgery |
| Safety Issue: | |
| Description: | The rate of breast conservative surgery among the patients receiving surgery |
| Measure: | Total pathologic complete response (tpCR) |
| Time Frame: | At time of surgery |
| Safety Issue: | |
| Description: | No residual invasive cancer in breast and ipsilateral axilla |
| Measure: | Analysis of biomarkers based on baseline specimen and residual tumor |
| Time Frame: | Baseline and at time of surgery |
| Safety Issue: | |
| Description: | Ki67 expression
cDNA microarray: gene expression profiling |
| Measure: | Association between clinical response rate and circulating tumor cells (CTCs) |
| Time Frame: | Baseline and at time of surgery |
| Safety Issue: | |
| Description: | Association between clinical response rate and circulating tumor cells (CTCs)
: CTCs are measured by CytoGen (SEOUL, KOREA)" |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Unknown status |
| Lead Sponsor: | Gangnam Severance Hospital |
Trial Keywords
- Breast cancer
- HER2
- ER
- Postmenopausal
- Trastuzumab
- Letrozole
- Neoadjuvant endocrine treatment
Last Updated
February 15, 2018
