Clinical trial NCT02214004: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Breast cancer
HER2
ER
Postmenopausal
Trastuzumab
Letrozole
Neoadjuvant endocrine treatment
Lead sponsor: Gangnam Severance Hospital
Sponsor class: OTHER
Collaborators: name: Seoul National University Hospital
name: Severance Hospital
name: Samsung Medical Center
name: Asan Medical Center
First posted: 2014-08-12
Enrollment: 132
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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)"

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

Primary outcomes:
measure: The rate of pathologic complete response
timeFrame: At time of surgery
Secondary outcomes:
measure: Clinical Response Rate
timeFrame: At time of surgery
measure: Safety profiles for the preoperative use of concurrent trastuzumab and letrozole
timeFrame: Up to 3 months after surgery
measure: The rate of breast conservative surgery
timeFrame: Up to 3 weeks after surgery
measure: Total pathologic complete response (tpCR)
timeFrame: At time of surgery
measure: Analysis of biomarkers based on baseline specimen and residual tumor
timeFrame: Baseline and at time of surgery
measure: Association between clinical response rate and circulating tumor cells (CTCs)
timeFrame: Baseline and at time of surgery
Other outcomes:
Locations:
city: Anyang
country: Korea, Republic of
facility: Hallym University Sacred Heart Hospital
city: Busan
country: Korea, Republic of
facility: Inje University Pusan Paik Hospital
city: Cheonan
country: Korea, Republic of
facility: Dankook University Hospital
city: Goyang
country: Korea, Republic of
facility: Ilsan Paik Hospital
city: Goyang
country: Korea, Republic of
facility: National Cancer Center
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Kangbuk Samsung Hospital
city: Seoul
country: Korea, Republic of
facility: Korea Institute of Radiological and Medical Sciences
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Suwon
country: Korea, Republic of
facility: Ajou University School of Medicine
Study officials:
affiliation: Gangnam Severance Hospital
name: Joon Jeong, M.D.,Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: