Luminal (ER+ve and/or PgR+ve >=1%) invasive breast cancer not candidate to neo - adjuvant chemotherapy MedDRA version: 20.0 Level: SOC Classification code 10038604 Term: Reproductive system and breast disorders System Organ Class: 10038604 - Reproductive system and breast disorders
Conditions
Interventions
Product Name: Metformina a lento rilascio
Product Code: [nd]
Pharmaceutical Form: Tablet
INN or Proposed INN: METFORMINA CLORIDRATO
CAS Number: 1115-70-4
Current Sponsor code: 1115-70-4
Other descript
Sponsors
ENTE OSPEDALIERO OSPEDALI GALLIERA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Women with histologically confirmed luminal (ER+ve and/or PgR+ve =1%) operable IBC (cT1-2, cN0-1, Mx) candidate to elective surgery and not to neo-adjuvant treatment. Women with larger tumors who refuse neo-adjuvant chemotherapy before surgery can also be eligible. Luminal HER2+ve IBC and DCIS are also eligible. - Age >= 18 years - ECOG performance status =70%) - Participants must have normal organ and marrow function as defined below: o Leukocytes >=3,000/microliter o Absolute neutrophil count >=1,500/microliter o Platelets >=100,000/microliter o AST (SGOT)/ALT (SGPT) 45 mL/min - Female participants of child-bearing potential must agree to use contraception such as barrier method of birth control or abstinence, prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she has to inform her study physician immediately. The effects of Metformin on the developing human fetus at the recommended therapeutic dose are unknown. - Ability to understand and the willingness to sign a written informed consent document. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 84 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 36
Exclusion criteria
Exclusion criteria: - BMI 80 mg furosemide) - Current use of hormonal contraceptives or female hormones - Concomitant use of Topiramate or other carbonic anhydrase inhibitors (e.g., Zonisamide, Acetazolamide or Dichlorphenamide) - Pregnant or lactating women. - Pregnant women are excluded from this study because even though published data from post-marketing studies have not reported a clear association between Metformin and major birth defects, miscarriage, or adverse maternal or fetal outcomes when Metformin was used during pregnancy, these studies cannot definitely establish the absence of any Metformin associated risk because of methodological limitations, including small sample size and inconsistent comparator groups. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with Metformin, breastfeeding should be discontinued if the mother is treated with Metformin. Moreover, prolonged fasting is not recommended in pregnant woman. -Women who practice any type of intermittent fasting. -Women who will not have anyone available to assist them in case of need.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary interim objective: assess the safety of the experimental intervention based on the frequency of occurrence of a Dose Limiting Toxicity (DLT) in the first 14 participants assigned to the experimental treatment arm. A DLT is defined as a hypoglycemic event requiring permanent discontinuation of study treatment or any grade 3 or greater adverse event possibly, probably, or definitely related to the study drug. Primary objective: assess the effect of the combination of prolonged nightly fasting (=16 hours) and Metformin on the change of Ki67 labeling index (LI) in cancer tissue (IBC or DCIS, if IBC is absent) between pre-treatment biopsy and post treatment surgical specimen. Co-primary objective: evaluate the difference in post-treatment Ki67 LI in cancer adjacent DCIS (in the presence of IBC), if present, or IEN, defined as atypical ductal hyperplasia or atypical lobular hyperplasia (ALH) or lobular carcinoma in situ (LCIS), between the active treatment and the control group.;Secondary Objective: -to explore the effect of intervention on PP2A-GSK3ß-MCL-1 axis in pre-post treatment tissue levels -to measure the change on: HOMA index, highly sensitive CRP, C-peptide, IGF-I, IGFBP-1, IGFBP-3, free IGF-I, Hb1Ac, lipid profile, adipokines; -to correlate a NGS mutational profile panel focused on ER+ve with the response of Ki67 -to measure the difference of cell death by IHC for M30 in post- treatment samples between arms; -to measure the difference of pS6 by IHC in post- treatment samples between arms; -to assess safety and toxicities -to measure the change in psychological variables and quality of life between pre and post treatment and the effect modification by distress, anxiety or depression on the intervention effect on Ki67; -to correlate eating habits, tobacco/alcohol consumption with the response of Ki67 between arms; - to compare the area under the curve of glucose levels between arms and within the experimental arm according to different do | — |
Countries
Italy, United States
Contacts
Public ContactS.C. Oncologia Medica
E.O. Ospedali Galliera
Outcome results
None listed