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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by Seoul National University Hospital
Sponsor:
Information provided by (Responsible Party):
Seoul National University Hospital
ClinicalTrials.gov Identifier:
NCT01589367
First received: April 17, 2012
Last updated: May 28, 2013
Last verified: May 2013

April 17, 2012
May 28, 2013
May 2012
April 2014   (final data collection date for primary outcome measure)
Clinical response rate [ Time Frame: 24week(after completing medication, preoperatively) ] [ Designated as safety issue: Yes ]
Comparing with RECIST 1.1 From baseline to 24week(after completing medication, preoperatively)
Same as current
Complete list of historical versions of study NCT01589367 on ClinicalTrials.gov Archive Site
  • Pathologic complete response rate [ Time Frame: Postoperation(within 26weeks after starting medication) ] [ Designated as safety issue: Yes ]
  • Changes of Ki67(%) [ Time Frame: Baseline-4week(second core needle biopsy) ] [ Designated as safety issue: Yes ]
  • Breast conservation rate [ Time Frame: Baseline-postoperation(within 26weeks after starting medication) ] [ Designated as safety issue: Yes ]
  • Breast density change [ Time Frame: Baseline-24week(after completing medication, preoperatively) ] [ Designated as safety issue: Yes ]
  • Toxicity profile of letrozole and metformin [ Time Frame: throughout the study ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Neoadjuvant Letrozole Plus Metformin vs Letrozole Plus Placebo for ER-positive Postmenopausal Breast Cancer
Phase II Randomized Study of Neoadjuvant Metformin Plus Letrozole vs Placebo Plus Letrozole 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

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

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Hormone Receptor Positive Malignant Neoplasm of Breast
  • 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
    Other Name: Arm1_Metformin_experimental
  • Drug: 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
    Other Name: Arm2_Letrozole alone_Placebo
  • Experimental: Arm1_ Metformin
    Letrozole with concurrent metformin
    Intervention: Drug: Metformin
  • Placebo Comparator: Arm 2_ Letrole alone
    Letrozole with placebo
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
208
April 2015
April 2014   (final data collection date for primary outcome measure)

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
Female
18 Years to 80 Years
No
Contact: Wonshik Han, MD PhD 82-2-2072-1958 hanw@snu.ac.kr
Contact: Jisun Kim, MD 82-2-2072-0612 leticeclear@naver.com
Korea, Republic of
 
NCT01589367
KBCSG 013
Yes
Seoul National University Hospital
Seoul National University Hospital
Not Provided
Principal Investigator: Wonshik Han, MD PhD Seoul National University Hospital
Seoul National University Hospital
May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP