Clinical trial NCT01589367: Neoadjuvant Letrozole Plus Metformin vs Letrozole Plus Placebo for ER-positive Postmenopausal Breast Cancer
Official title: Phase II Randomized Study of Neoadjuvant Metformin Plus Letrozole vs Placebo Plus Letrozole for ER-positive Postmenopausal Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hormone Receptor Positive Malignant Neoplasm of Breast
Keywords: neoadjuvant endocrine therapy
metformin
postmenopausal breast cancer
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
First posted: 2012-05-01
Enrollment: 208
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Preoperative letrozole versus letrozole with metformin in postmenopausal Estrogen receptor positive breast cancer patients

Phase II multicenter 1:1 randomized clinical trial Total 208 patients

Primary endpoint Clinical response rate

Secondary endpoint Pathologic complete response rate Breast conserving surgery rate Percent mammographic density change Ki67(%) change after 4week medication of 2nd core needle biopsy Toxicity profile of neoadjuvant letrozole, metformin

Detailed description: To identify the anti-tumor effect of metformin with preoperatively given letrozole in postmenopausal estrogen receptor positive breast cancer patients

Eligibility criteria: Inclusion Criteria:

* Estrogen receptor positive breast cancer
* Clinically measurable tumor size(stage II/III)
* No evidence of distant metastasis
* Postmenopause women 'Age≥60yr' OR 'previous bilateral oophorectomy' OR 'FSH\>30 with no bleeding history within 1yr'
* ECOG 0-2
* Adequate hepatorenal, bone marrow function 'serum Cr\<1.4mg/dL' AND 'Bilirubin\< upper limit of normal x 1.5 AND 'AST/ALT \< upper limit of normal x 1.8 AND 'ALP \< upper limit of normal x 1.8 AND 'Hemoglobin \>10 g/dL' AND 'ANC \>1,500/mm3' AND 'Platelet \>100,000/mm3'
* Spontaneous signed into the written informed consent

Exclusion Criteria:

* Who does not meet the above inclusion criteria
* History of other carcinoma
* Uncontrolled infection
* History of psychiatric, epileptic disease
* Male breast cancer
* Diabetes 'HbA1c≥6.5' OR 'FBS≥126mg/dL'
* Hypersensitivity or intolerance to metformin
* Risk of metformin associated lactic acidosis 'Congestive heart disease of NYHA Class llll/IV' OR 'History of other acidosis' OR 'Alcohol intake more than either 3 bottles beer OR 1 bottle Soju'
* During medication of metformin, sulfonylureas, thiazolidinediones, insulin
* Diffuse microcalcification in mammogram
* Multiple OR bilateral OR inflammatory breast cancer
* Chemotherapy or endocrine therapy within 2yr due to history of breast cancer

Primary outcomes:
measure: Clinical response rate
timeFrame: 24week(after completing medication, preoperatively)
Secondary outcomes:
measure: Pathologic complete response rate
timeFrame: Postoperation(within 26weeks after starting medication)
measure: Changes of Ki67(%)
timeFrame: Baseline-4week(second core needle biopsy)
measure: Breast conservation rate
timeFrame: Baseline-postoperation(within 26weeks after starting medication)
measure: Breast density change
timeFrame: Baseline-24week(after completing medication, preoperatively)
measure: Toxicity profile of letrozole and metformin
timeFrame: throughout the study
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
affiliation: Seoul National University Hospital
name: Wonshik Han, MD PhD
role: PRINCIPAL_INVESTIGATOR
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