Clinical Trial: NCT01589367 - My Cancer Genome

NCT01589367

Description:

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

Related Conditions:

Breast Carcinoma

Recruiting Status:

Completed

Phase:

Phase 2

URL:

https://clinicaltrials.gov/show/NCT01589367

Trial Eligibility

Document

Title

Brief Title: 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

Clinical Trial IDs

ORG STUDY ID: KBCSG 013
NCT ID: NCT01589367

Conditions

Hormone Receptor Positive Malignant Neoplasm of Breast

Interventions

Drug	Synonyms	Arms
Metformin	Arm1_Metformin_experimental	Arm1_ Metformin
Placebo	Arm2_Letrozole alone_Placebo	Arm 2_ Letrole alone

Purpose

Detailed Description

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

Trial Arms

Name	Type	Description	Interventions
Arm1_ Metformin	Experimental	Letrozole with concurrent metformin	Metformin
Arm 2_ Letrole alone	Placebo Comparator	Letrozole with placebo	Placebo

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

Maximum Eligible Age:	80 Years
Minimum Eligible Age:	18 Years
Eligible Gender:	Female
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Clinical response rate
Time Frame:	24week(after completing medication, preoperatively)
Safety Issue:
Description:	Comparing with RECIST 1.1 From baseline to 24week(after completing medication, preoperatively)

Secondary Outcome Measures

Measure:	Pathologic complete response rate
Time Frame:	Postoperation(within 26weeks after starting medication)
Safety Issue:
Description:	In case that under postoperative biopsy, residual breast cancer cell is not present in primary lesion and lymph node.

Measure:	Changes of Ki67(%)
Time Frame:	Baseline-4week(second core needle biopsy)
Safety Issue:
Description:	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.

Measure:	Breast conservation rate
Time Frame:	Baseline-postoperation(within 26weeks after starting medication)
Safety Issue:
Description:	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)

Measure:	Breast density change
Time Frame:	Baseline-24week(after completing medication, preoperatively)
Safety Issue:
Description:	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).

Measure:	Toxicity profile of letrozole and metformin
Time Frame:	throughout the study
Safety Issue:
Description:	based on NCI-CTCAE version 4.0

Details

Phase:	Phase 2
Primary Purpose:	Interventional
Overall Status:	Completed
Lead Sponsor:	Seoul National University Hospital

Trial Keywords

neoadjuvant endocrine therapy
metformin
postmenopausal breast cancer

Last Updated

September 10, 2018

Clinical Trials /

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