Neoadjuvant Letrozole Plus Metformin vs Letrozole Plus Placebo for ER-positive Postmenopausal Breast Cancer

NCT01589367 | Completed Phase 2 DMC

• 1 other identifier: KBCSG 013
• Study Type: interventional
• Target: 208
• Locations: 1 country
• Sites: 1

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

Conditions

Hormone Receptor Positive Malignant Neoplasm of Breast

Keywords

neoadjuvant endocrine therapy; metformin; postmenopausal breast cancer

Outcome Measures

Primary Outcomes (1)

• Clinical response rate

  Comparing with RECIST 1.1 From baseline to 24week(after completing medication, preoperatively)

  24week(after completing medication, preoperatively)

Secondary Outcomes (5)

• Pathologic complete response rate

  Postoperation(within 26weeks after starting medication)

• Changes of Ki67(%)

  Baseline-4week(second core needle biopsy)

• Breast conservation rate

  Baseline-postoperation(within 26weeks after starting medication)

• Breast density change

  Baseline-24week(after completing medication, preoperatively)

• Toxicity profile of letrozole and metformin

  throughout the study

Study Arms (2)

Arm1_ Metformin

EXPERIMENTAL

Letrozole with concurrent metformin

Drug: Metformin

Arm 2_ Letrole alone

PLACEBO COMPARATOR

Letrozole with placebo

Drug: Placebo

Interventions

Metformin DRUG

Metformin 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

Also known as: Arm1_Metformin_experimental

Arm1_ Metformin

Placebo DRUG

Letrozole 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

Also known as: Arm2_Letrozole alone_Placebo

Arm 2_ Letrole alone

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Seoul National University Hospital: lead

Study Sites (1)

Seoul National University Hospital

Seoul, 110-744, South Korea

Location

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MeSH Terms

Interventions

Metformin

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Wonshik Han, MD PhD

  Seoul National University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2012
• First Posted: May 1, 2012
• Study Start: May 1, 2012
• Primary Completion: April 1, 2018
• Study Completion: August 1, 2018
• Last Updated: September 10, 2018

Record last verified: 2017-06

Locations

KR (1)