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
  Purpose

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


Condition Intervention Phase
Hormone Receptor Positive Malignant Neoplasm of Breast
Drug: Metformin
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase II Randomized Study of Neoadjuvant Metformin Plus Letrozole vs Placebo Plus Letrozole for ER-positive Postmenopausal Breast Cancer

Resource links provided by NLM:


Further study details as provided by Seoul National University Hospital:

Primary Outcome Measures:
  • 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)


Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 208
Study Start Date: May 2012
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm1_ Metformin
Letrozole with concurrent metformin
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
Placebo Comparator: Arm 2_ Letrole alone
Letrozole with placebo
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

Detailed Description:

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

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01589367

Contacts
Contact: Wonshik Han, MD PhD 82-2-2072-1958 hanw@snu.ac.kr
Contact: Jisun Kim, MD 82-2-2072-0612 leticeclear@naver.com

Locations
Korea, Republic of
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of, 110-744
Contact: Wonshik Han, MD PhD    82-2-2072-1958    hanw@snu.ac.kr   
Contact: Jisun Kim, MD    82-2-2072-0612    leticeclear@naver.com   
Sub-Investigator: Jisun Kim, MD         
Sponsors and Collaborators
Seoul National University Hospital
Investigators
Principal Investigator: Wonshik Han, MD PhD Seoul National University Hospital
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Seoul National University Hospital
ClinicalTrials.gov Identifier: NCT01589367     History of Changes
Other Study ID Numbers: KBCSG 013
Study First Received: April 17, 2012
Last Updated: May 28, 2013
Health Authority: South Korea: Institutional Review Board

Keywords provided by Seoul National University Hospital:
neoadjuvant endocrine therapy
metformin
postmenopausal breast cancer

Additional relevant MeSH terms:
Neoplasms
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Metformin
Letrozole
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 16, 2014