Neoadjuvant Trastuzumab and Letrozole for Postmenopausal Women

Phase 2

• Conditions: Breast Cancer
• Interventions: Drug: Trastuzumab; Drug: Letrozole

• Registration Number: NCT02214004
• Lead Sponsor: Gangnam Severance Hospital

Brief Summary

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)"

Study Timeline

• Study First Submitted: 2014-08-05
• Study First Submitted QC: 2014-08-09
• Study First Posted: 2014-08-12
• Study Start: 2015-03
• Status Verified: 2018-02
• Last Update Submitted: 2018-02-13
• Last Update Posted: 2018-02-15
• Primary Completion: 2019-03
• Study Completion: 2019-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 132

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Trastuzumab and Letrozole	Letrozole	- Concurrently initiate two drugs on Day 1 of Cycle 1
Trastuzumab and Letrozole	Trastuzumab	- Concurrently initiate two drugs on Day 1 of Cycle 1

Primary Outcome Measures

Name	Time	Method
The rate of pathologic complete response	At time of surgery	No residual invasive cancer in breast regardless of axilla

Secondary Outcome Measures

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

Trial Locations

Locations (14)

Hallym University Sacred Heart Hospital; 🇰🇷 Anyang, Korea, Republic of

Inje University Pusan Paik Hospital; 🇰🇷 Busan, Korea, Republic of

Gangnam Severance Hospital; 🇰🇷 Seoul, Korea, Republic of

Ilsan Paik Hospital; 🇰🇷 Goyang, Korea, Republic of

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

Kangbuk Samsung Hospital; 🇰🇷 Seoul, Korea, Republic of

Korea Institute of Radiological and Medical Sciences; 🇰🇷 Seoul, Korea, Republic of

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

Ajou University School of Medicine; 🇰🇷 Suwon, Korea, Republic of

Dankook University Hospital; 🇰🇷 Cheonan, Korea, Republic of

National Cancer Center; 🇰🇷 Goyang, Korea, Republic of

Korea University Anam Hospital; 🇰🇷 Seoul, Korea, Republic of

Seoul Medical Center; 🇰🇷 Seoul, Korea, Republic of