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
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

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

Dr Bernardo Bonanni
Scientific

Divisione di Prevenzione e Genetica Oncologica
Istituto Europeo di Oncologia
via Ripamonti, 435
Milan
20141
Italy

Email bernardo.bonanni@ieo.it

Study information

Study designRandomized double-blind placebo-controlled phase II presurgical study
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific titleA presurgical phase II study on activity of metformin on breast cancer cell proliferation
Study objectivesWe 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) studiedBreast cancer
Intervention1. 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 typeDrug
Pharmaceutical study type(s)
PhasePhase II
Drug / device / biological / vaccine name(s)Metformin
Primary outcome measure1. 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 measures1. 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 date01/12/2008
Completion date30/09/2011

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexFemale
Target number of participants200
Total final enrolment274
Key inclusion criteria1. 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 criteria1. 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 enrolment01/12/2008
Date of final enrolment30/09/2011

Locations

Countries of recruitment

  • Italy

Study participating centre

Istituto Europeo di Oncologia
Milan
20141
Italy

Sponsor information

European Institute of Oncology (Istituto Europeo di Oncologia) (Italy)
Research organisation

Via Ripamonti, 435
Milan
20141
Italy

Phone +39 02 574 891
Email carlo.ciani@ieo.it
Website http://www.ieo.it/Italiano/Pages/Default.aspx
ROR logo "ROR" https://ror.org/02vr0ne26

Funders

Funder type

Charity

Italian League Against Cancer (ref: 14/08)

No information available

Ministero della Salute
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 shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot 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.