PIK3CA mutated, HR+/Her2- metastatic breast cancer who do not present progressive disease after 6-8 cycles of 1st or second line chemotherapy.
Conditions
Interventions
Product Name: Alpelisib
Product Code: BYL719
Pharmaceutical Form: Tablet
Trade Name: FASLODEX
Pharmaceutical Form: Solution for injection
INN or Proposed INN: FULVESTRANT
Other descriptive name: FULV
Sponsors
UNICANCER
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Women (or men) with histologically confirmed metastatic breast cancer. 2. Hormone receptor positive (HR+) and no Her2 over-expression, according to local assessment. 3. Presence of PIK3CA mutation on exon 9 or 20, determined on metastatic tissue specimen (frozen or FFPE) or plasma (ctDNA). Eligible plasma should have been collected at time of metastatic disease progression and before to initiating chemotherapy. 4. Patient’s disease is resistant to endocrine therapy (defined either as a relapse or progression occurred during endocrine therapy, whatever the line, or less than 12 months after the end of endocrine therapy in adjuvant context). 5. Patients who received 6 to 8 cycles of a first line chemotherapy, or patients who received 6 to 8 cycles of a first line stopped for progression followed by 6 to 8 cycles of a 2nd line chemotherapy, and who are presenting a stable or a responding disease at the time of randomization (4 full cycles of chemotherapy are accepted if stopped for toxicity reasons). 6. Age = 18 years 7. WHO Performance Status 0/1 8. Presence of measurable or evaluable disease according to RECIST criteria v1.1 9. Patients will have had a wash-out period of at least 14 days for weekly (except monoclonal antibodies) or daily chemotherapies or 28 days for other chemotherapies from last chemotherapy administration prior to randomization and should have recovered from all residual toxicities (grade =1), excluding alopecia. 10. Patient has adequate bone marrow and organ function as defined by the following laboratory values: a. Absolute Neutrophil Count (ANC) = 1.5 x 109/L b. Platelets = 100 x 109/L c. Hemoglobin = 9.0 g/dL d. INR = 1.5 e. Potassium, magnesium and calcium (corrected for albumin), within normal limits for the institution, or = Grade 1 severity according to NCI-CTCAE version 4.03 if judged clinically not significant by the investigator f. Serum creatinine = 1.5 x ULN and/or creatinine clearance = 50mL/min (Measured or calculated by Cockroft and Gault formula) g. Total serum bilirubin = ULN (or = 1.5 x ULN if liver metastases are present; or total bilirubin = 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert’s Syndrome) h. Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) = 2.5 ULN (or =65 years) yes F.1.3.1 Number of subjects for this age range 45
Exclusion criteria
Exclusion criteria: 1. Spinal cord compression and/or symptomatic or progressive brain metastases (unless asymptomatic or treated and stable without steroids during the last 30 days). 2. Patient has received more than 2 previous lines of chemotherapy for metastatic disease before randomization. 3. In the Investigator’s judgment, patient has a life expectancy < 3 months . 4. Disease progression occuring before randomization. 5. Patient has received prior treatment with any PI3K or AKT inhibitor (mTOR inhibitors are allowed) 6. Patient has history of hypersensitivity to any drugs or metabolites of similar chemical classes as alpelisib, or history of hypersensitivity to active or inactive excipients of any other study treatment 7. Patient has not recovered to grade 1 or better (except alopecia) from related side effects of any prior antineoplastic therapy 8. Patient has received radiotherapy = 4 weeks or limited field radiation for palliation = 2 weeks prior to randomization, and who has not recovered to grade 1 or better from related side effects of such therapy (with the exception of alopecia) and/or from whom = 25% of the bone marrow was irradiated 9. Patient has participated to another clinical study with an investigational product during the last 30 days. 10. Patient has had major surgery within 14 days prior to starting study treatment or has not recovered from major side effects 11. Patient is currently receiving or has received systemic corticosteroids = 2 weeks prior to starting study treatment, or has not fully recovered from side effects of such treatment (grade =1). 12. Patients with an established diagnosis of diabetes mellitus type I or not controlled type II, or documented steroid induced diabetes mellitus 13. Patient who necessitates to maintain the following drugs during study treatment: • Drugs known to be strong inhibitors or inducers of isoenzyme CYP3A4 including herbal medications (list of prohibited CYP3A4 inhibitors and inducers provided in Table 12) • Drugs with a known risk to induce Torsades de Pointes (list of prohibited QT prolonging drugs provided in Table 12) Note: The patient must have discontinued strong inducers for at least one week and must have discontinued strong inhibitors before the study treatment is initiated. Switching to a different medication prior to starting study treatment is allowed. 14. Patient is currently receiving warfarin or other coumarin derived anti-coagulant for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed. 15. Patients who have other concurrent severe and/or uncontrolled medical conditions that would, in the Investigator’s judgment, contraindicate patient participation in the individual patient program (eg. active or uncontrolled severe infection, chronic active hepatitis, immuno-compromised, acute or chronic pancreatitis, uncontrolled high blood pressure, interstitial lung disease, etc.)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To determine whether treatment with alpelisib plus fulvestrant prolongs progression-free survival (PFS) compared to maintenance chemotherapy in patients PIK3CA mutated with hormone receptor positive (HR+), HER2-negative advanced breast cancer, who do not present a progressive disease after 6-8 cycles of chemotherapy. ;Secondary Objective: - To pool data from a sample of patients from the SAFIR-PI3K trial with the SAFIR02 Breast trial data in order to address the primary objective of the SAFIR02 Breast trial. - To compare overall survival - To evaluate overall response rates and change in tumor size in each arm - To evaluate the safety of each arm - To compare overall survival in the pooled data from the SAFIR02 Breast trial and the sample of patients of the SAFIR-PI3K trial - To evaluate overall response rates and change in tumor size in each arm in the pooled data from the SAFIR02 Breast trial and the sample of patients of the SAFIR-PI3K trial - To evaluate the safety of each arm in the pooled data from the SAFIR02 Breast trial and a sample of patients from the SAFIR-PI3K trial - To merge part of the SAFIR-PI3K study data to the SAFIR02 Breast trial in order to perform a prospective pooled analysis of SAFIR02 Lung and SAFIR02 Breast studies ;Primary end point(s): Progression free survival.;Timepoint(s) of evaluation of this end point: When the required number of events has been reached. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): _;Timepoint(s) of evaluation of this end point: _ | — |
Countries
France
Contacts
Public ContactMarta JIMENEZ
UNICANCER
Outcome results
None listed