Neoadjuvant Trastuzumab and Letrozole for Postmenopausal Women (HERAKLES)

Yonsei University Health System (YUHS)

Status and phase: Unknown; Phase 2

Conditions: Breast Cancer

Treatments: Drug: Letrozole; Drug: Trastuzumab

Study type: Interventional

Funder types: Other

Identifiers

NCT02214004

HERAKLES

Details and patient eligibility

About

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.

Full 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)"

Enrollment: 132 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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132 participants in 1 patient group

Trastuzumab and Letrozole

Experimental group

Description:

- Concurrently initiate two drugs on Day 1 of Cycle 1

Treatment:

Drug: Letrozole

Drug: Trastuzumab