Condition category
Cancer
Date applied
21/07/2011
Date assigned
05/08/2011
Last edited
10/02/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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 measures

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

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

http://www.ieo.it/Italiano/Pages/Default.aspx

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

Federal/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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

10/02/2016: Plain English summary added.