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

• Status: Recruiting
• Trial end date: 2022-12-31
• Target enrollment: 0
• Participant gender: All

Summary

Men and post- or induced menopausal women with ER[+] and/or PgR[+], HER2[- ] advanced BC, with centrally-confirmed PI3KCAMut who progressed to an aromatase inhibitor (AI) regimen.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: MedSIR
• Collaborator: Novartis
• Treatments: Fulvestrant; Metformin

Criteria

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[+] 8.

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.9.

8. Presence of PIK3CAMut

9. Progression on an AI regimen for advanced BC

10. (CNS) metastasis, controlled local disease without corticoids and/or anti-epileptic medication is required.

11. At least one prior line of endocrine therapy for advanced disease, or progression on, or within 12 months from completion of a (neo) adjuvant aromatase inhibitor.

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) and HbA1c < 5,7 to 6.4%

14. Adequate organ function

15. Patients willing and able to comply with scheduled visits

16. Resolution of all acute toxic effects of prior anti-cancer therapy

Exclusion Criteria:

1. Prior treatment with a PI3K, mTOR or AKT inhibitor

2. Prior therapy with fulvestrant for advanced BC

3. Patients with a known hypersensitivity to alpelisib or fulvestrant, or to any of the excipients

4. Patients with an established diagnosis of diabetes mellitus [DM] type I or II requiring anti-diabetic drugs

5. Prior treatment with metformin.

6. More than one prior line of chemotherapy for advanced disease.

7. Inflammatory BC at screening.

8. Patients receiving systemic corticosteroids within 1 week prior to start treatment with alpelisib (BYL719).

9. Patients with past medical history of acute or chronic pancreatitis within 1 year prior to screening.

10. Patient with impaired gastrointestinal (GI) function

11. Patient with documented pneumonitis/interstitial lung disease

12. Patients with clinically significant uncontrolled heart disease and/or recent cardiac events

13. Subject has any other concurrent severe and/or uncontrolled medical condition

14. 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

15. Patients with Child-Pugh score B or C liver disease.

16. Patients with renal failure.

17. Patients with unresolved osteonecrosis of the jaw

18. Subject has a history of Stevens-Johnson Syndrome (SJS), erythema multiforme (EM) or toxic epidermal necrolysis (TEN)

19. Subject has received radiotherapy ≤ 4 weeks or limited field radiation for palliation

• 2 weeks prior to randomization

20. 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

21. Participation in a prior investigational study within 30 days prior to the start of study treatment

22. Subject has not recovered from all toxicities related to prior anticancer therapies to NCI CTCAE version 4.03 Grade ≤1.

23. Subject has a concurrent malignancy or malignancy within 3 years of start of study treatment

24. Subject has a known history of (HIV) infection.

25. Subject has any other concurrent severe and/or uncontrolled medical condition

26. Subject is not able to understand and to comply with study instructions and requirements.

27. Subject is breastfeeding or pregnant woman

28. 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.