Neoadjuvant Trastuzumab and Letrozole for Postmenopausal Women

Breast Cancer Clinical Trial

— HERAKLES  

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 Details — Status: Recruiting

Administrative data

• NCT number: NCT02214004
• Other study ID #: HERAKLES
• Status: Recruiting
• Phase: Phase 2
• First received: August 5, 2014
• Last updated: February 13, 2018
• Start date: March 2015
• Est. completion date: June 2019

Study information

• Verified date: February 2018
• Source: Gangnam Severance Hospital
• Contact: Joon Jeong, M.D.,Ph.D.
• Phone: 82220193370
• Email: gsjjoon[@]yuhs.ac
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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)"

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 132
• Est. completion date: June 2019
• Est. primary completion date: March 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

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
• Letrozole
- Daily letrozole 2.5 mg/day for 24 weeks

Locations

Country	Name	City	State
Korea, Republic of	Hallym University Sacred Heart Hospital	Anyang
Korea, Republic of	Inje University Pusan Paik Hospital	Busan
Korea, Republic of	Dankook University Hospital	Cheonan
Korea, Republic of	Ilsan Paik Hospital	Goyang
Korea, Republic of	National Cancer Center	Goyang
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Gangnam Severance Hospital	Seoul
Korea, Republic of	Kangbuk Samsung Hospital	Seoul
Korea, Republic of	Korea Institute of Radiological and Medical Sciences	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Ajou University School of Medicine	Suwon

Sponsors (5)

Lead Sponsor	Collaborator
Gangnam Severance Hospital	Asan Medical Center, Samsung Medical Center, Seoul National University Hospital, Severance Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

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