A presurgical phase II study on activity of metformin on breast cancer cell proliferation
| ISRCTN | ISRCTN16493703 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN16493703 |
| EudraCT/CTIS number | 2008-004912-10 |
| Secondary identifying numbers | IEO S425/408 |
- Submission date
- 21/07/2011
- Registration date
- 05/08/2011
- Last edited
- 23/10/2020
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Plain English summary of protocol
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
Contact information
Scientific
Divisione di Prevenzione e Genetica Oncologica
Istituto Europeo di Oncologia
via Ripamonti, 435
Milan
20141
Italy
| bernardo.bonanni@ieo.it |
Study information
| Study design | Randomized double-blind placebo-controlled phase II presurgical study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | A presurgical phase II study on activity of metformin on breast cancer cell proliferation |
| Study objectives | 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(s) | European Institute of Oncology IRB, 16/10/2008 |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | 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 study start date | 01/12/2008 |
| Completion date | 30/09/2011 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Female |
| Target number of participants | 200 |
| Total final enrolment | 274 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 01/12/2008 |
| Date of final enrolment | 30/09/2011 |
Locations
Countries of recruitment
- Italy
Study participating centre
20141
Italy
Sponsor information
Research organisation
Via Ripamonti, 435
Milan
20141
Italy
| Phone | +39 02 574 891 |
|---|---|
| carlo.ciani@ieo.it | |
| Website | http://www.ieo.it/Italiano/Pages/Default.aspx |
"ROR" |
https://ror.org/02vr0ne26 |
Funders
Funder type
Charity
No information available
Government organisation / National government
- Alternative name(s)
- Italian Ministry of Health, Italy Ministry of Health, Ministry of Health of Italy, Ministry of Health - Italy, Ministry of Health, Italy
- Location
- Italy
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/03/2014 | 23/10/2020 | Yes | No |
Editorial Notes
23/10/2020: The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.
10/02/2016: Plain English summary added.
