Neoadjuvant Trastuzumab and Letrozole for Postmenopausal Women (HERAKLES)

February 13, 2018 updated by: Joon Jeong, Gangnam Severance Hospital

A Phase II Trial of Preoperative HER2 Targeting and Endocrine Therapy in Postmenopausal Women With HER2 and HR Positive Breast Cancer

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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)"

Study Type

Interventional

Enrollment (Anticipated)

132

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Korea, Republic of
      • Anyang, Korea, Republic of
        • Recruiting
        • Hallym University Sacred Heart Hospital
        • Contact:
      • Busan, Korea, Republic of
        • Not yet recruiting
        • Inje University Pusan Paik Hospital
        • Contact:
          • Taehyun Kim, M.D.,Ph.D.
      • Cheonan, Korea, Republic of
        • Recruiting
        • Dankook University Hospital
        • Contact:
          • Junwon Min, M.D.,Ph.D.
      • Goyang, Korea, Republic of
      • Goyang, Korea, Republic of
        • Not yet recruiting
        • National Cancer Center
        • Contact:
      • Seoul, Korea, Republic of
        • Recruiting
        • Seoul National University Hospital
        • Contact:
      • Seoul, Korea, Republic of
        • Not yet recruiting
        • Asan Medical Center
        • Contact:
          • Byung Ho Son, M.D.,Ph.D.
      • Seoul, Korea, Republic of
        • Recruiting
        • Korea University Anam Hospital
        • Contact:
          • Jeoung Won Bae, M.D.,Ph.D.
      • Seoul, Korea, Republic of
      • Seoul, Korea, Republic of
      • Seoul, Korea, Republic of, 135720
        • Recruiting
        • Gangnam Severance Hospital
        • Contact:
        • Contact:
      • Seoul, Korea, Republic of
        • Recruiting
        • Korea Institute of Radiological and Medical Sciences
        • Contact:
      • Seoul, Korea, Republic of
        • Recruiting
        • Seoul Medical Center
        • Contact:
          • Dong Hui Cho
      • Suwon, Korea, Republic of
        • Not yet recruiting
        • Ajou University School of Medicine
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
Other Names:
  • Herceptin
Drug: Letrozole
- Daily letrozole 2.5 mg/day for 24 weeks
Other Names:
  • Femara

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The rate of pathologic complete response
Time Frame: At time of surgery
No residual invasive cancer in breast regardless of axilla
At time of surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Response Rate
Time Frame: At time of surgery
Clinical response includes complete response, partial response and stable disease.
At time of surgery
Safety profiles for the preoperative use of concurrent trastuzumab and letrozole
Time Frame: Up to 3 months after surgery
Toxicity according to CTCAE protocol from the initiated day to 3 months after surgery
Up to 3 months after surgery
The rate of breast conservative surgery
Time Frame: Up to 3 weeks after surgery
The rate of breast conservative surgery among the patients receiving surgery
Up to 3 weeks after surgery
Total pathologic complete response (tpCR)
Time Frame: At time of surgery
No residual invasive cancer in breast and ipsilateral axilla
At time of surgery
Analysis of biomarkers based on baseline specimen and residual tumor
Time Frame: Baseline and at time of surgery
  • Ki67 expression
  • cDNA microarray: gene expression profiling
Baseline and at time of surgery
Association between clinical response rate and circulating tumor cells (CTCs)
Time Frame: Baseline and at time of surgery

Association between clinical response rate and circulating tumor cells (CTCs)

: CTCs are measured by CytoGen (SEOUL, KOREA)"
Baseline and at time of surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gangnam Severance Hospital

Collaborators

Samsung Medical Center
Asan Medical Center
Seoul National University Hospital
Severance Hospital

Investigators

  • Principal Investigator: Joon Jeong, M.D.,Ph.D., Gangnam Severance Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2015

Primary Completion (Anticipated)

March 1, 2019

Study Completion (Anticipated)

June 1, 2019

Study Registration Dates

First Submitted

August 5, 2014

First Submitted That Met QC Criteria

August 9, 2014

First Posted (Estimate)

August 12, 2014

Study Record Updates

Last Update Posted (Actual)

February 15, 2018

Last Update Submitted That Met QC Criteria

February 13, 2018

Last Verified

February 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HERAKLES

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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