Clinical Trials /

Study Assessing the Efficacy and Safety of Alpelisib Plus Fulvestrant in Men and Postmenopausal Women With Advanced Breast Cancer Which Progressed on or After Aromatase Inhibitor Treatment.

NCT02437318

Description:

To determine whether treatment with alpelisib plus fulvestrant prolongs progression-free survival compared to fulvestrant and placebo in men and postmenopausal women with hormone receptor positive (HR+), HER2-negative advanced breast cancer, who received prior treatment with an Aromatase Inhibitor either as (neo)adjuvant or for advanced disease.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study Assessing the Efficacy and Safety of Alpelisib Plus Fulvestrant in Men and Postmenopausal Women With Advanced Breast Cancer Which Progressed on or After Aromatase Inhibitor Treatment.
  • Official Title: A Phase III Randomized Double-blind, Placebo Controlled Study of Alpelisib in Combination With Fulvestrant for Men and Postmenopausal Women With Hormone Receptor Positive, HER2-negative Advanced Breast Cancer Which Progressed on or After Aromatase Inhibitor Treatment

Clinical Trial IDs

  • ORG STUDY ID: CBYL719C2301
  • SECONDARY ID: 2015-000340-42
  • NCT ID: NCT02437318

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
FulvestrantFaslodexfulvestrant + alpelisib
Alpelisibfulvestrant + alpelisib
Alpelisib placebofulvestrant + placebo

Purpose

To determine whether treatment with alpelisib plus fulvestrant prolongs progression-free survival compared to fulvestrant and placebo in men and postmenopausal women with hormone receptor positive (HR+), HER2-negative advanced breast cancer, who received prior treatment with an Aromatase Inhibitor either as (neo)adjuvant or for advanced disease.

Trial Arms

NameTypeDescriptionInterventions
fulvestrant + alpelisibExperimentalAlpelisib (300 mg; oral; once daily) in combination with fulvestrant (500 mg; intramuscular injection on Day 1 and Day 15 of Cycle 1, and then Day 1 of each subsequent 28-day cycle)
  • Fulvestrant
  • Alpelisib
fulvestrant + placeboPlacebo ComparatorPlacebo (300 mg; oral; once daily) in combination with fulvestrant (500 mg; intramuscular injection on Day 1 and Day 15 of Cycle 1, and then Day 1 of each subsequent 28-day cycle)
  • Fulvestrant
  • Alpelisib placebo

Eligibility Criteria

        Inclusion Criteria:

          -  If female, patient is postmenopausal

          -  Patient has identified PIK3CA status

          -  Patients may be:

               -  relapsed with documented evidence of progression while on (neo) adjuvant
                  endocrine therapy or within 12 months from completion of (neo)adjuvant endocrine
                  therapy with no treatment for metastatic disease;

               -  relapsed with documented evidence of progression more than 12 months from
                  completion of (neo)adjuvant endocrine therapy and then subsequently; progressed
                  with documented evidence of progression while on or after only one line of
                  endocrine therapy for metastatic disease;

               -  newly diagnosed advanced breast cancer, then relapsed with documented evidence of
                  progression while on or after only one line of endocrine therapy

          -  Patient has recurrence or progression of disease during or after AI therapy (i.e.

        letrozole, anastrozole, exemestane).

          -  Patient has a histologically and/or cytologically confirmed diagnosis of
             estrogen-receptor positive breast cancer by local laboratory and has HER2 negative
             breast cancer

          -  Patient has either measurable disease per RECIST 1.1 criteria OR at least one
             predominantly lytic bone lesion must be present

          -  Patient has adequate bone marrow function

        Exclusion Criteria:

          -  Patient with symptomatic visceral disease or any disease burden that makes the patient
             ineligible for endocrine therapy per the investigator's best judgment

          -  Patient has received prior treatment with chemotherapy (except for neoadjuvant/
             adjuvant chemotherapy), fulvestrant, any PI3K, mTOR or AKT inhibitor (pre-treatment
             with CDK4/6 inhibitors is allowed)

          -  Patient with inflammatory breast cancer at screening

          -  Patients with Child pugh score B or C

          -  Patients with an established diagnosis of diabetes mellitus type I or not controlled
             type II

          -  Patient has Eastern Cooperative Oncology Group (ECOG) performance status 2 or more

          -  Patient with CNS involvement unless he/she is at least 4 weeks from prior therapy
             completion to starting the study treatment and has stable CNS tumor at time of
             screening and not receiving steroids and/or enzyme inducing ant-epileptic medications
             for brain metastases

          -  Patient has participated in a prior investigational study within 30 days prior to
             enrollment or within 5 half-lives of the investigational product, whichever is longer

          -  Patient has a history of acute pancreatitis within 1 year of screening or a past
             medical history of chronic pancreatitis

          -  Patient who relapsed with documented evidence of progression more than 12 months from
             completion of (neo)adjuvant endocrine therapy with no treatment for metastatic disease

        Other protocol-defined inclusion/esclusion criteria may apply.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free Survival (PFS) Per Investigator Assessment in the PIK3CA Mutant Cohort
Time Frame:Once approximately 243 PFS events in this cohort had been observed, up to 32 months
Safety Issue:
Description:PFS, defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. PFS will be assessed via a local radiology assessment according to RECIST 1.1

Secondary Outcome Measures

Measure:Overall Survival (OS) for Patients With PI3KCA Mutant Status
Time Frame:Up to approximatly 59 months
Safety Issue:
Description:OS is defined as the time from date of randomization to date of death due to any cause.
Measure:Overall Response Rate (ORR)
Time Frame:Up to approximatly 36 months
Safety Issue:
Description:ORR is defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST 1.1.
Measure:Time to Definitive Deterioration of Eastern Cooperative Oncology Group (ECOG) Performance Status
Time Frame:Baseline, Up to approximatly 36 months
Safety Issue:
Description:Deterioration of Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
Measure:Safety and Tolerability of Alpelisib in Combination With Fulvestrant
Time Frame:Up to approximatly 37 months
Safety Issue:
Description:Safety will be determined by type, frequency and severity of adverse events per CTCAEv4.03 and type, frequency and severity of laboratory toxicities per CTCAEv4.03. Patients will be followed up for the duration of the study.
Measure:Time to 10% Deterioration in the Global Health Status/Quality of Life (QOL) Scale Score of the EORTC QLQ-C30
Time Frame:Up to approximatly 36 months
Safety Issue:
Description:Composite measure of change from baseline in the domain scores, health states, overall health status, and index values at the time of each assessment will be summarized
Measure:Plasma Concentration-time Profile of Alpelisib Given in Combinatio With Fulvestrant and Appropriate Pharmacokinetics (PK) Parameters
Time Frame:Day 8 and Day 15 of Cycle 1, then Day 1 of Cycles 2,4, 6, 8
Safety Issue:
Description:Assessment of any potential impact of fulvestrant on the pharmacokinetics of alpelisib by collection of sparse and trough PK samples. PK parameters includes,but not limited to, Cmin, Cmax, t1/2, AUClast for alpelisib (and any relevant metabolites) and fulvestrant
Measure:PFS Based on Radiology Assessments and Using RECIST 1.1 Criteria
Time Frame:Baseline, Up to approximatly 36 months
Safety Issue:
Description:PFS in patients with PIK3CA mutant status and patients with PIK3CA non-mutant status as measured in ctDNA.
Measure:Clinical Benefit Rate (CBR)
Time Frame:Up to approximatly 36 months
Safety Issue:
Description:Clinical benefit rate is defined as the proportion of patients with a best overall response of CR or PR or SD or Non-CR/Non-PD lasting more than 24 weeks based on local investigator assessment.
Measure:Change in the Global Health Status/(QOL) Scale Score of the EORTC QLQ-C30
Time Frame:Baseline, Up to approximatly 36 months
Safety Issue:
Description:Composite measure of change from baseline in the domain scores, health states, overall health status, and index values at the time of each assessment will be summarized
Measure:Summary Statistics of Fulvestrant and Alpelisib Plasma Concentrations
Time Frame:Day 8 and Day 15 of Cycle 1, then Day 1 of Cycles 2,4, 6, 8
Safety Issue:
Description:Assessment of any potential impact of fulvestrant on the pharmacokinetics of alpelisib by collection of sparse and trough PK samples.
Measure:PFS for Patients With PIK3CA Non-mutant Status
Time Frame:Up to approximatly 36 months
Safety Issue:
Description:PFS based on local radiology assessments and using RECIST 1.1 criteria in the PIK3CA non-mutant cohort
Measure:OS for Patients With PIK3CA Non-mutant Status
Time Frame:Up to approximatly 59 months
Safety Issue:
Description:OS is defined as the time from date of randomization to date of death due to any cause.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • BYL719
  • HR+
  • HER2-negative
  • advanced breast cancer
  • alpelisib
  • fulvestrant
  • PI3K
  • Phase III
  • ER+
  • PgR+
  • men
  • postmenopausal
  • aromatase inhibitor
  • neoplasms

Last Updated

August 11, 2021