Study to Evaluate the Effect of Metformin in the Prevention of HG in HR[+]/HER2[-] PIK3CA-mut Advanced BC Patients (METALLICA)

This is an interventional treatment trial for Breast Cancer focused on measuring ER, PI3KMut, HER2, Metastatic, unresectable, breast, hyperglycemia, men Read More

Inclusion Criteria:

1. Signed Informed Consent Form (ICF)Exclusion Criteria:
2. Male or female patients ≥ 18 years of age at the time of signing ICF.
3. Men and pre-menopausal women should have been treated with (LHRH) analogue
4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
5. Histologically proven diagnosed of advanced BC not amenable to curative treatment.
6. Documented recurrent ER[+] and/or PgR[+]
7. Measurable or evaluable disease as per RECIST v.1.1 criteria.Patients with no measurable or evaluable disease will be considered by the study medical monitor.
8. Presence of PIK3CAMut
9. No more than 2 prior lines of endocrine therapy for ABC. Regimen with documented evidence of progression while on (neo)adjuvant endocrine therapy or within the first 12 months from completion of (neo)adjuvant endocrine therapy will be considered as a prior line.
10. Progression on an AI regimen for advanced BC
11. Patients are permitted to have received previous fulvestrant either as (neo)adjuvant regimen or as first-line regimen for metastatic disease.
12. No more than one prior chemotherapy-containing regimen for the treatment of metastatic disease is permitted.

13. Fasting plasma glucose (FPG) and Glycosylated Hemoglobin (HbA1c):

    Cohort A: FPG ≤100 mg/dL (5.6 mmol/L) and HbA1c < 5,7

    Cohort B: FPG 100 mg/dL (5.6 mmol/L) to 140 mg/dL (7.8 mmol/L) (IFG) or HbA1c < 5,7 to 6.4%

14. (CNS) metastasis, controlled local disease without corticoids and/or anti-epileptic medication is required.
15. Adequate organ function
16. Patients willing and able to comply with scheduled visits
17. Resolution of all acute toxic effects of prior anti-cancer therapy

Exclusion Criteria:

1. Prior treatment with a PI3K, mTOR or AKT inhibitor
2. Patients with a known hypersensitivity to alpelisib or fulvestrant, or to any of the excipients
3. Patients with an established diagnosis of diabetes mellitus [DM] type I or II requiring anti-diabetic drugs. Patients with a high-risk FPG or HbA1c as per inclusion criterion #14 are eligible to enter the cohort B if no anti-diabetic drug were received in the last 14 days prior to the start of study treatment.
4. Inflammatory BC at screening.
5. Subject has a concurrent malignancy or malignancy within 3 years of start of study treatment.
6. Patients with past medical history of acute or chronic pancreatitis within 1 year prior to screening.
7. Patient with impaired gastrointestinal (GI) function
8. Patient with documented pneumonitis/interstitial lung disease
9. Patients with Child-Pugh score B or C liver disease.
10. Patients with renal failure.
11. Patients with unresolved osteonecrosis of the jaw.
12. Subject has a history of Stevens-Johnson Syndrome (SJS), erythema multiforme (EM) or toxic epidermal necrolysis (TEN) or or Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).
13. Uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) ≥ 160 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 100 mm Hg, with or without antihypertensive medication.
14. Patients with clinically significant uncontrolled heart disease and/or recent cardiac events
15. Subject has any other concurrent severe and/or uncontrolled medical condition

16. Subject is currently receiving any of the following medications and cannot be discontinued 7 days prior to the start of the treatment:

    • Strong inhibitors or inducers of the isoenzyme CYP3A within the last 5 days prior to study entry.
    • Inhibitors of BCRP
17. Subject has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to randomization
18. Subject is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to starting study drug, or who have not fully recovered from side effects of such treatment
19. Participation in a prior investigational study within 30 days prior to the start of study treatment
20. Subject has not recovered from all toxicities related to prior anticancer therapies to NCI CTCAE version 4.03 Grade ≤1.
21. Subject has a known history of (HIV) infection.
22. Subject has any other concurrent severe and/or uncontrolled medical condition
23. Patient is a breastfeeding or pregnant woman
24. Women of child-bearing potential, unless they are using highly effective methods of contraception during study treatment and for one month after the last dose of any study treatment.
25. Subject is a sexually active male unwilling to use a condom during intercourse while taking study treatment, and up to 6 months after stopping study treatment.