Plain English Summary
Background and study aims
Metformin is a commonly used, cheap and safe drug for treating diabetes. Research has shown that metformin use seems to be associated to a reduction in breast cancer risk. We are interested in investigating the effect of metformin given for 4 weeks in non-diabetic patients with breast cancer.
Who can participate?
Breast cancer patients aged over 18
What does the study involve?
Participants are randomly allocated to be treated with either metformin or a placebo (dummy) drug until they undergo surgery. The effect of the drug on the cancer cells and on various blood parameters is measured.
What are the possible benefits and risks of participating?
The expected risks are mainly gastrointestinal symptoms (diarrhea and nausea), so patients are asked to take a half dose during the first 3 days of treatment and then to continue to full dose if no symptoms occur. There is a very rare risk of lactic acidosis, an acute metabolic dysfunction which may happen especially in subjects with kidney disease.
Where is the study run from?
European Institute of Oncology, Milan (Italy)
When is the study starting and how long is it expected to run for?
December 2008 to September 2011
Who is funding the study?
The Italian League against Cancer and the Ministry of Health. Drug and placebo are provided at no cost by Laboratori Guidotti SpA, Pisa (Italy).
Who is the main contact?
Dr Bernardo Bonanni
bernardo.bonanni@ieo.it
Trial website
Contact information
Type
Scientific
Primary contact
Dr Bernardo Bonanni
ORCID ID
Contact details
Divisione di Prevenzione e Genetica Oncologica
Istituto Europeo di Oncologia
via Ripamonti
435
Milan
20141
Italy
-
bernardo.bonanni@ieo.it
Additional identifiers
EudraCT number
2008-004912-10
ClinicalTrials.gov number
Protocol/serial number
IEO S425/408
Study information
Scientific title
A presurgical phase II study on activity of metformin on breast cancer cell proliferation
Acronym
Study hypothesis
We assess the antiproliferative activity of metformin in a window-of-opportunity trial in non-diabetic women with breast cancer candidates to surgery.
Ethics approval
European Institute of Oncology IRB, 16/10/2008
Study design
Randomized double-blind placebo-controlled phase II presurgical study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Breast cancer
Intervention
1. Patients are randomized in a double blind fashion to metformin (850 mg bid) or placebo and treated for 4 weeks
2. During the first three days of treatment patients are asked to take half dose (850 mg/die) in order to adapt to gastrointestinal symptoms
Intervention type
Drug
Phase
Phase II
Drug names
Metformin
Primary outcome measure
1. The short-term response in the proliferative antigen Ki-67 LI, which is increasingly being used to screen active drugs in breast cancer because of its prognostic value and its postulated role in predicting the efficacy of anti cancer drugs
2. Percent change in Ki-67 LI between pretreatment biopsy and post-treatment surgical specimen
Secondary outcome measures
1. Effect of metformin on Ki-67 based on change in Homa index
2. Effect of metformin on circulating biomarkers (lipid profile, CRP, testosterone, adypokines, C-peptide, insulin, glycemia)
3. Evaluation of the antiproliferative activity of metformin on hyperplastic, dysplastic and malignant breast tissue
Overall trial start date
01/12/2008
Overall trial end date
30/09/2011
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Age >18 years
2. Performance status=0 (Southwest Oncology Group [SWOG])
3. Histologically-confirmed breast cancer not candidate to neoadjuvant therapy,
no prior treatment for breast cancer
4. Signed informed consent
Participant type
Patient
Age group
Adult
Gender
Female
Target number of participants
200
Participant exclusion criteria
1. Previous treatment for breast cancer, including chemotherapy and endocrine therapy
2. Known severe hypersensitivity to metformin or any of the excipients of this product
3. Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or in situ cervical cancer
4. As judged by the investigator, any evidence of severe or uncontrolled systemic disease (e.g. unstable or uncompensated respiratory, cardiac, hepatic, or renal disease) that would prevent subjects from undergoing any of the treatment options or would prevent prolonged follow-up
5. Diabetes mellitus and diabetesÂ’ treatments
6. Creatinine >1.2 mg/dl and/or Glomerular filtration > 60 ml/min/1.73m2
7. Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the subject to participate in the study
8. Pregnancy or breast feeding (women of child-bearing potential must have a negative pregnancy test within 7 days before the start of study treatment and should practice acceptable methods of birth control to prevent pregnancy during and after study treatment)
9. Treatment with a non-approved or investigational drug within 30 days before day 1 of study treatment
Recruitment start date
01/12/2008
Recruitment end date
30/09/2011
Locations
Countries of recruitment
Italy
Trial participating centre
Istituto Europeo di Oncologia
Milan
20141
Italy
Sponsor information
Organisation
European Institute of Oncology (Istituto Europeo di Oncologia) (Italy)
Sponsor details
Via Ripamonti
435
Milan
20141
Italy
+39 02 574 891
carlo.ciani@ieo.it
Sponsor type
Research organisation
Website
Funders
Funder type
Charity
Funder name
Italian League Against Cancer (ref: 14/08)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Ministero della Salute
Alternative name(s)
Ministry of Health, Italy
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
Italy
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list