Hormone Receptor Positive Malignant Neoplasm of Breast | Neoadjuvant Letrozole Plus Metformin vs Letrozole Plus Placebo for ER-positive Postmenopausal Breast Cancer
Hormone Receptor Positive Malignant Neoplasm of Breast research study
What is the primary objective of this study?
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
Who is eligible to participate?
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
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Hormone Receptor Positive Malignant Neoplasm of Breast
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Drug:MetforminMetformin HCl 500mg(morning/evening) PO daily x 1week Metformin HCl 1000mg(morning)and 500mg(evening)PO daily x 1week Metformin HCl 1000mg(morning/evening) PO daily x 22weeks
Drug:PlaceboLetrozole 2.5mg PO daily + Placebo 1 tablet PO 2/day x 1week Letrozole 2.5mg PO daily + Placebo 2 tablet+ 1 tablet PO x 1 week Letrozole 2.5mg PO daily + Placebo 2 tablet PO 2/day x 22 weeks
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
Arm1_ MetforminLetrozole with concurrent metformin
Arm 2_ Letrole aloneLetrozole with placebo
Start Date: May 2012
Completed Date: April 2017
Phase: Phase 2
Primary Outcome: Clinical response rate
Secondary Outcome: Pathologic complete response rate
Study sponsors, principal investigator, and references
Principal Investigator: Wonshik Han, MD PhD
Lead Sponsor: Seoul National University Hospital
Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A, Fisher ER, Wickerham DL, Begovic M, DeCillis A, Robidoux A, Margolese RG, Cruz AB Jr, Hoehn JL, Lees AW, Dimitrov NV, Bear HD. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol. 1998 Aug;16(8):2672-85.