Clinical trial NCT01275859: Neoadjuvant Combined Endocrine and HER2 Target Therapy in Postmenopausal Women With ER and Her2 Positive Breast Cancer
Official title: Neoadjuvant Letrozole and Lapatinib in Postmenopausal Women With ER and Her2 Positive Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Neoadjuvant
Letrozole
Lapatinib
Postmenopausal
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
First posted: 2011-01-13
Enrollment: 25
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: Cross-talk between epidermal growth factors and the ER occurs at multiple levels and seems to play a crucial role in breast cancer progression and endocrine resistance.Combined HER1/HER2-targeted therapy with aromatase inhibitors for ER-positive and HER-2 positive postmenopausal breast cancer might enhance response and block emergence of endocrine resistant tumor.

Detailed description: 1. To evaluate the efficacy of the neoadjuvant combination therapy with letrozole and lapatinib in postmenopausal patients with ER-positive and HER2-positive breast cancer.
2. To assess markers predictive of treatment response and outcome in this setting.

Eligibility criteria: Inclusion Criteria:

* Written informed consent
* Female patients
* Histologically confirmed invasive breast cancer
* Primary tumor greater than 2cm diameter, measured by sonography
* N0-3 (any N if resectable) and no evidence of distant metastasis (M) (isolated supraclavicular node involvement allowed)
* ER positive (intermediate and strong positive)
* HER2 positive (IHC3+ or FISH positive in case of IHC 2+)
* No evidence of metastasis (M0)
* No prior hormonal, chemotherapy or radiotherapy is allowed
* No breast operation other than biopsy to make diagnosis is allowed
* Postmenopausal women with ECOG Performance Status of 0 or 1
* Postmenopausal, as defined by any of the following:
* At least 55 years of age
* Under 55 years of age and amenorrheic for at least 12 months OR follicle-stimulating hormone (FSH) values ≥ 30 IU/L and estradiol levels ≤ 20 IU/L
* Prior bilateral oophorectomy or prior radiation castration with amenorrhea for at least 6 months
* Adequate hematopoietic, renal, hepatic function:

Exclusion Criteria:

* Patients who received hormonal, chemotherapy or radiotherapy for breast cancer
* Patients who underwent surgery for breast cancer
* Patients with bilateral invasive breast cancer
* Patients with inflammatory breast cancer (T4d)
* Patients without primary tumor (T0) Inability to perform \[18F\]FES PET imaging due to physical inability, claustrophobia, or other mental illness.
* ER poor disease as defined locally (e.g: Allred score 1-3, H-score\<100)
* Patients who have history of cancer other than in situ uterine cervix cancer or non-melanotic skin cancer
* Chronic daily treatment with aspirin (\>325mg/day) or clopidogrel (\>75mg/day)
* Chronic daily treatment with corticosteroids (dose of \>10mg /day ethylprednisolone equivalent)
* Clinically significant cardiovascular disease: CVA/stroke (\<6month prior to enroll), MI (\<6month prior to enroll), unstable angina, NYHA Grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication.
* Hormone replacement therapy within 4 weeks of starting treatment
* Known hypersensitivity to any of the study drugs including ditosylate monohydrate salt
* Pregnant or nursing mother (if applicable)

Primary outcomes:
measure: pCR
timeFrame: 2010 Nov- 2012 May
Secondary outcomes:
measure: SUV for [18F]FES PET
timeFrame: 2010 Nov- 2012 May
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Nedical Center
Study officials:
affiliation: Asan Medical Center
name: Sung-Bae Kim, MD
role: PRINCIPAL_INVESTIGATOR
References: