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

Hormone Receptor Positive Malignant Neoplasm of Breast Clinical Trial

Official title:

Phase II Randomized Study of Neoadjuvant Metformin Plus Letrozole vs Placebo Plus Letrozole for ER-positive Postmenopausal Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01589367
• Other study ID #: KBCSG 013
• Status: Completed
• Phase: Phase 2
• Start date: May 2012
• Est. completion date: August 2018

Study information

• Verified date: June 2017
• Source: Seoul National University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 208
• Est. completion date: August 2018
• Est. primary completion date: April 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Hormone Receptor Positive Malignant Neoplasm of Breast
• Neoplasms

Intervention

Drug:
• Metformin
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
• Placebo
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

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Seoul National University Hospital

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (31)

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* Note: There are 31 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical response rate	Comparing with RECIST 1.1 From baseline to 24week(after completing medication, preoperatively)	24week(after completing medication, preoperatively)
Secondary	Pathologic complete response rate	In case that under postoperative biopsy, residual breast cancer cell is not present in primary lesion and lymph node.	Postoperation(within 26weeks after starting medication)
Secondary	Changes of Ki67(%)	IHC is performed for formalin-fixed paraffin embedded tissue at the central laboratory. Ki67 is recorded as % and percentage reduction of baseline and Ki67 expressed cell on day28 are compared.	Baseline-4week(second core needle biopsy)
Secondary	Breast conservation rate	Before pre-operative anti hormone therapy, the patients are classified into following three types; Candidate for BCS; Marginal for breast conservation surgery; Candidate for mastectomy only; Inoperable by standard mastectomy Classification of each type shall be determined by each researcher of each institution subjectively. For future separate objective analysis, central institution will collect image file of mammography of each patient.; Type of operation being actually performed in each type is compared. (BCS vs mastectomy)	Baseline-postoperation(within 26weeks after starting medication)
Secondary	Breast density change	Percent mammographic density (%) of cranial-caudal view of opposite breast is measured/compared based on continued variable by using validated computer-assisted thresholding program called Cumulus software (University Toronto, Toronto, Ontario, Canada).	Baseline-24week(after completing medication, preoperatively)
Secondary	Toxicity profile of letrozole and metformin	based on NCI-CTCAE version 4.0	throughout the study