Neoadjuvant Trastuzumab and Letrozole for Postmenopausal Women (HERAKLES)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified August 2014 by Gangnam Severance Hospital
Sponsor:
Collaborators:
Seoul National University Hospital
Severance Hospital
Samsung Medical Center
Asan Medical Center
Information provided by (Responsible Party):
Joon Jeong, Gangnam Severance Hospital
ClinicalTrials.gov Identifier:
NCT02214004
First received: August 5, 2014
Last updated: August 9, 2014
Last verified: August 2014
  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.


Condition Intervention Phase
Breast Cancer
Drug: Trastuzumab
Drug: Letrozole
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Preoperative HER2 Targeting and Endocrine Therapy in Postmenopausal Women With HER2 and HR Positive Breast Cancer

Resource links provided by NLM:


Further study details as provided by Gangnam Severance Hospital:

Primary Outcome Measures:
  • The rate of pathologic complete response [ Time Frame: At time of surgery ] [ Designated as safety issue: No ]
    No residual invasive cancer in breast regardless of axilla


Secondary Outcome Measures:
  • Clinical Response Rate [ Time Frame: At time of surgery ] [ Designated as safety issue: No ]
  • Safety profiles for the preoperative use of concurrent trastuzumab and letrozole [ Time Frame: Up to 3 months after surgery ] [ Designated as safety issue: Yes ]
  • The rate of breast conservative surgery [ Time Frame: Up to 3 weeks after surgery ] [ Designated as safety issue: No ]
  • Total pathologic complete response (tpCR) [ Time Frame: At time of surgery ] [ Designated as safety issue: No ]
    No residual invasive cancer in breast and ipsilateral axilla

  • Analysis of biomarkers based on baseline specimen and residual tumor [ Time Frame: Baseline and at time of surgery ] [ Designated as safety issue: No ]
    • Ki67 expression
    • cDNA microarray: gene expression profiling

  • Association between clinical response rate and circulating tumor cells (CTCs) [ Time Frame: Baseline and at time of surgery ] [ Designated as safety issue: No ]
    Association between clinical response rate and circulating tumor cells (CTCs)


Estimated Enrollment: 132
Study Start Date: August 2014
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Trastuzumab and Letrozole
- Concurrently initiate two drugs on Day 1 of Cycle 1
Drug: Trastuzumab

- Eight times IV administration of trastuzumab per 3 weeks

  • Trastuzumab 8mg/kg on Day 1 of Cycle 1
  • Trastuzumab 6mg/kg from Day 1 of Cycle 2 to Day 1 of Cycle 8
Drug: Letrozole
- Daily letrozole 2.5 mg/day for 24 weeks

Detailed Description:

Eligibility 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

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)
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02214004

Contacts
Contact: Joon Jeong, M.D.,Ph.D. 82220193370 gsjjoon@yuhs.ac
Contact: Sung Gwe Ahn, M.D. 82220194402 asg2004@yuhs.ac

Sponsors and Collaborators
Gangnam Severance Hospital
Seoul National University Hospital
Severance Hospital
Samsung Medical Center
Asan Medical Center
Investigators
Principal Investigator: Joon Jeong, M.D.,Ph.D. Gangnam Severance Hospital
  More Information

No publications provided

Responsible Party: Joon Jeong, Professor, Gangnam Severance Hospital
ClinicalTrials.gov Identifier: NCT02214004     History of Changes
Other Study ID Numbers: HERAKLES
Study First Received: August 5, 2014
Last Updated: August 9, 2014
Health Authority: Korea: Food and Drug Administration

Keywords provided by Gangnam Severance Hospital:
Breast cancer
HER2
ER
Postmenopausal
Trastuzumab
Letrozole
Neoadjuvant endocrine treatment

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Letrozole
Trastuzumab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 11, 2014