Clinical Trials /

Neoadjuvant Trastuzumab and Letrozole for Postmenopausal Women

NCT02214004

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

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

  • Breast Cancer

Interventions

DrugSynonymsArms
TrastuzumabHerceptinTrastuzumab and Letrozole
LetrozoleFemaraTrastuzumab 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

NameTypeDescriptionInterventions
Trastuzumab and LetrozoleExperimental- Concurrently initiate two drugs on Day 1 of Cycle 1
  • Trastuzumab
  • Letrozole

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:Recruiting
Lead Sponsor:Gangnam Severance Hospital

Trial Keywords

  • Breast cancer
  • HER2
  • ER
  • Postmenopausal
  • Trastuzumab
  • Letrozole
  • Neoadjuvant endocrine treatment

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