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Completed

NCT Number: NCT01589367

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

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

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Key information

Conditions

Hormone Receptor Positive Malignant Neoplasm of Breast

Age range

18 year–80 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 2

Primary location

Seoul National University Hospital

Seoul, 110-744, South Korea

About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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

Other names: Arm1_Metformin_experimental

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

Other names: Arm2_Letrozole alone_Placebo

Primary outcomes

  1. Clinical response rate

    Time frame: 24week(after completing medication, preoperatively)

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

Secondary outcomes

  1. Pathologic complete response rate

    Time frame: Postoperation(within 26weeks after starting medication)

    In case that under postoperative biopsy, residual breast cancer cell is not present in primary lesion and lymph node.

  2. Changes of Ki67(%)

    Time frame: Baseline-4week(second core needle biopsy)

    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.

  3. Breast conservation rate

    Time frame: Baseline-postoperation(within 26weeks after starting medication)

    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)

  4. Breast density change

    Time frame: Baseline-24week(after completing medication, preoperatively)

    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).

  5. Toxicity profile of letrozole and metformin

    Time frame: throughout the study

    based on NCI-CTCAE version 4.0

Sponsors and collaborators

Lead sponsor

Seoul National University Hospital

Other

Registry information

Official study title

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

Important dates

Study start
2012
Primary completion
2018
Study completion
2018
First posted
May 1, 2012
Registry last updated
Sep 10, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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