Neoadjuvant Trastuzumab and Letrozole for Postmenopausal Women (HERAKLES)
Primary Purpose
Breast Cancer
Status
Unknown status
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Trastuzumab
Letrozole
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer focused on measuring Breast cancer, HER2, ER, Postmenopausal, Trastuzumab, Letrozole, Neoadjuvant endocrine treatment
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
Sites / Locations
- Hallym University Sacred Heart HospitalRecruiting
- Inje University Pusan Paik Hospital
- Dankook University HospitalRecruiting
- Ilsan Paik HospitalRecruiting
- National Cancer Center
- Gangnam Severance HospitalRecruiting
- Asan Medical Center
- Kangbuk Samsung HospitalRecruiting
- Korea Institute of Radiological and Medical SciencesRecruiting
- Korea University Anam HospitalRecruiting
- Samsung Medical Center
- Seoul Medical CenterRecruiting
- Seoul National University HospitalRecruiting
- Ajou University School of Medicine
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Trastuzumab and Letrozole
Arm Description
- Concurrently initiate two drugs on Day 1 of Cycle 1
Outcomes
Primary Outcome Measures
The rate of pathologic complete response
No residual invasive cancer in breast regardless of axilla
Secondary Outcome Measures
Clinical Response Rate
Clinical response includes complete response, partial response and stable disease.
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
The rate of breast conservative surgery
The rate of breast conservative surgery among the patients receiving 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)
Association between clinical response rate and circulating tumor cells (CTCs)
: CTCs are measured by CytoGen (SEOUL, KOREA)"
Full Information
NCT ID
NCT02214004
First Posted
August 5, 2014
Last Updated
February 13, 2018
Sponsor
Gangnam Severance Hospital
Collaborators
Seoul National University Hospital, Severance Hospital, Samsung Medical Center, Asan Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT02214004
Brief Title
Neoadjuvant Trastuzumab and Letrozole for Postmenopausal Women
Acronym
HERAKLES
Official Title
A Phase II Trial of Preoperative HER2 Targeting and Endocrine Therapy in Postmenopausal Women With HER2 and HR Positive Breast Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
February 2018
Overall Recruitment Status
Unknown status
Study Start Date
March 2015 (undefined)
Primary Completion Date
March 2019 (Anticipated)
Study Completion Date
June 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Gangnam Severance Hospital
Collaborators
Seoul National University Hospital, Severance Hospital, Samsung Medical Center, Asan Medical Center
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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)"
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
Breast cancer, HER2, ER, Postmenopausal, Trastuzumab, Letrozole, Neoadjuvant endocrine treatment
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
132 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Trastuzumab and Letrozole
Arm Type
Experimental
Arm Description
- Concurrently initiate two drugs on Day 1 of Cycle 1
Intervention Type
Drug
Intervention Name(s)
Trastuzumab
Other Intervention Name(s)
Herceptin
Intervention Description
- 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
Intervention Type
Drug
Intervention Name(s)
Letrozole
Other Intervention Name(s)
Femara
Intervention Description
- Daily letrozole 2.5 mg/day for 24 weeks
Primary Outcome Measure Information:
Title
The rate of pathologic complete response
Description
No residual invasive cancer in breast regardless of axilla
Time Frame
At time of surgery
Secondary Outcome Measure Information:
Title
Clinical Response Rate
Description
Clinical response includes complete response, partial response and stable disease.
Time Frame
At time of surgery
Title
Safety profiles for the preoperative use of concurrent trastuzumab and letrozole
Description
Toxicity according to CTCAE protocol from the initiated day to 3 months after surgery
Time Frame
Up to 3 months after surgery
Title
The rate of breast conservative surgery
Description
The rate of breast conservative surgery among the patients receiving surgery
Time Frame
Up to 3 weeks after surgery
Title
Total pathologic complete response (tpCR)
Description
No residual invasive cancer in breast and ipsilateral axilla
Time Frame
At time of surgery
Title
Analysis of biomarkers based on baseline specimen and residual tumor
Description
Ki67 expression
cDNA microarray: gene expression profiling
Time Frame
Baseline and at time of surgery
Title
Association between clinical response rate and circulating tumor cells (CTCs)
Description
Association between clinical response rate and circulating tumor cells (CTCs)
: CTCs are measured by CytoGen (SEOUL, KOREA)"
Time Frame
Baseline and at time of surgery
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Joon Jeong, M.D.,Ph.D.
Phone
82220193370
Email
gsjjoon@yuhs.ac
First Name & Middle Initial & Last Name or Official Title & Degree
Sung Gwe Ahn, M.D.
Phone
82220194402
Email
asg2004@yuhs.ac
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joon Jeong, M.D.,Ph.D.
Organizational Affiliation
Gangnam Severance Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hallym University Sacred Heart Hospital
City
Anyang
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lee Su Kim, M.D.,Ph.D.
Email
lskim0503@hallym.ac.kr
Facility Name
Inje University Pusan Paik Hospital
City
Busan
Country
Korea, Republic of
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Taehyun Kim, M.D.,Ph.D.
Facility Name
Dankook University Hospital
City
Cheonan
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Junwon Min, M.D.,Ph.D.
Facility Name
Ilsan Paik Hospital
City
Goyang
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jae Il Kim, M.D., Ph.D.
Email
erythrokim@paik.ac.kr
Facility Name
National Cancer Center
City
Goyang
Country
Korea, Republic of
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eun Sook Lee, M.D.,Ph.D.
Email
eslee@ncc.re.kr
Facility Name
Gangnam Severance Hospital
City
Seoul
ZIP/Postal Code
135720
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joon Jeong, M.D.,Ph.D.
Phone
82220193370
Email
gsjjoon@yuhs.ac
First Name & Middle Initial & Last Name & Degree
Sung Gwe Ahn, M.D.
Phone
82220193370
Email
asg2004@yuhs.ac
Facility Name
Asan Medical Center
City
Seoul
Country
Korea, Republic of
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Byung Ho Son, M.D.,Ph.D.
Facility Name
Kangbuk Samsung Hospital
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chan Heun Park, M.D.,Ph.D.
Email
chanheun.park@samsung.com
Facility Name
Korea Institute of Radiological and Medical Sciences
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Woo Chul Noh, M.D.,Ph.D.
Phone
8229701280
Email
nohwoo@kcch.re.kr
Facility Name
Korea University Anam Hospital
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jeoung Won Bae, M.D.,Ph.D.
Facility Name
Samsung Medical Center
City
Seoul
Country
Korea, Republic of
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Seok Jin Nam, M.D.,Ph.D.
Email
seokjin.nam@samsung.com
Facility Name
Seoul Medical Center
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dong Hui Cho
Facility Name
Seoul National University Hospital
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wonshik Han, M.D.,Ph.D.
Email
hanw@snu.ac.kr
Facility Name
Ajou University School of Medicine
City
Suwon
Country
Korea, Republic of
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yongsik Jung, M.D.,Ph.D.
Email
drjys@ajou.ac.kr
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Neoadjuvant Trastuzumab and Letrozole for Postmenopausal Women
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