Clinical Trials /

Study Assessing the Efficacy and Safety of Alpelisib Plus Fulvestrant or Letrozole, Based on Prior Endocrine Therapy, in Patients With PIK3CA Mutation With Advanced Breast Cancer Who Have Progressed on or After Prior Treatments

NCT03056755

Description:

Study assessing the efficacy and safety of alpelisib plus fulvestrant or letrozole, based on prior endocrine therapy, in patients with PIK3CA mutation with advanced breast cancer who have progressed on or after prior treatments

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study Assessing the Efficacy and Safety of Alpelisib Plus Fulvestrant or Letrozole, Based on Prior Endocrine Therapy, in Patients With PIK3CA Mutation With Advanced Breast Cancer Who Have Progressed on or After Prior Treatments
  • Official Title: BYLieve: A Phase II, Multicenter, Open-label, Three-cohort, Non- Comparative Study to Assess the Efficacy and Safety of Alpelisib Plus Fulvestrant or Letrozole in Patients With PIK3CA Mutant, Hormone Receptor (HR) Positive, HER2-negative Advanced Breast Cancer (aBC), Who Have Progressed on or After Prior Treatments

Clinical Trial IDs

  • ORG STUDY ID: CBYL719X2402
  • NCT ID: NCT03056755

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
alpelisibBYL719Prior CDK 4/6 + aromatase
fulvestrantPrior CDK 4/6 + aromatase
letrozolePrior CDK 4/6 + fulvestrant
GoserelinPrior CDK 4/6 + fulvestrant
LeuprolidePrior CDK 4/6 + fulvestrant

Purpose

Study assessing the efficacy and safety of alpelisib plus fulvestrant or letrozole, based on prior endocrine therapy, in patients with PIK3CA mutation with advanced breast cancer who have progressed on or after prior treatments

Trial Arms

NameTypeDescriptionInterventions
Prior CDK 4/6 + aromataseExperimentalPatients who received any CDK 4/6 inhibitor plus aromatase inhibitor as treatment (immediately prior) will receive alpelisib 500 mg oral.+ fulvestrant 500 mg intramuscular (i.m)
  • alpelisib
  • fulvestrant
Prior CDK 4/6 + fulvestrantExperimentalPatients who received any CDK 4/6 inhibitor plus fulvestrant as treatment (immediately prior) will receive alpelisib 300 mg oral + letrozole 2.5 mg oral
  • alpelisib
  • letrozole
  • Goserelin
  • Leuprolide
Prior systemic chemo or ETExperimentalPatients who received systemic chemotherapy or endrocrine therapy (ET) as immediate prior treatment will receive alpelisib 300 mg oral + fulvestrant 500 mg i.m.
  • alpelisib
  • fulvestrant

Eligibility Criteria

        Inclusion Criteria:

          -  Patient is male or female 18 years or older

          -  Males or females with advanced (locoregionally recurrent or metatstatic) breast cancer
             not amenable to curative therapy

          -  In case of women, both premenopausal and postmenopausal patients are allowed to be
             included in study; menopausal status is relevant for the requirement of LHRH agonist
             (examples for use in this study include but not limited to goserelin, leuprolide or
             locally available treatment) to be used concomitantly with alpelisib and
             letrozole/fulvestrant

               1. Patient is postmenopausal woman defined as either:

                    -  Prior bilateral oophorectomy or

                    -  Age ≥60 or

                    -  Age <60 and amenorrhea for 12 or more months (in the absence of
                       chemotherapy, tamoxifen, toremifene, or ovarian suppression) and FSH and/or
                       estradiol in the postmenopausal range per local normal range.

                  If patient is taking tamoxifen or toremifene and age <60, then FSH and plasma
                  estradiol levels should be in post-menopausal range per local normal range.

                  Note: For women using therapy-induced amenorrhea other than ovarian radiation,
                  goserelin or leuprolide, etc., serial measurements of FSH and/or estradiol are
                  needed to ensure menopausal status

               2. Patient is premenopausal defined as either:

                    -  Patient had last menstrual period within the last 12 months or

                    -  If on tamoxifen or toremifene with in the past 14 days, plasma estradiol and
                       FSH must be in the premenopausal range per local normal range, or

                    -  In case of therapy induced amenorrhea, plasma estradiol and/or FSH must be
                       in the premenopausal range per local normal range

          -  Patient has histological and/or cytological confirmed ER+ and/or PgR+ aBC

          -  Patient has confirmed HER2-negative advanced breast cancer (aBC)

          -  Patient has a PIK3CA mutation confirmed by Novartis designated central lab or patient
             has a pathology report confirming PIK3CA mutant status by certified laboratory (using
             validated PI3KCA mutation assay) either from tissue or blood and must (mandatory) send
             tumor tissue to Novartis designated central lab for confirmation of mutational status

          -  Patient must have:

               -  Documented evidence of tumor progression on or after CDK 4/ 6 inhibitor
                  combination treatment; CDK 4/6 inhibitor must be the last treatment regimen prior
                  to study entry,

               -  AI treatment (either in adjuvant or metastatic setting) and received systemic
                  chemotherapy or ET as last treatment regimen in cohort C

               -  Maintenance therapies, where applicable, must be regarded as part of the main
                  treatment.

               -  No more than two (2) prior anti-cancer therapies for aBC

               -  Received no more than one prior regimen of chemotherapy in the metastatic setting

          -  Patient has either measurable disease per RECIST v1.1 or at least one predominantly
             lytic bone lesion must be present

          -  ECOG performance status ≤ 2

          -  Patient has fasting plasma glucose (FPG) ≤140 mg/dL (7.7 mmol/L) and glycosylated
             hemoglobin (HbA1c) ≤ 6.4% (both criteria have to be met)

          -  Patient has adequate bone marrow, coagulation, liver and renal function

        Exclusion Criteria:

          -  patient has known hypersensitivity to alpelisib, fulvestrant or letrozole

          -  Patient has received prior treatment with any PI3K inhibitors

          -  Patient with an established diagnosis of diabetes mellitus type I or uncontrolled type
             II

          -  Patient has a concurrent malignancy or malignancy within 3 years of study screening
             period, with the exception of adequately treated, basal or squamous cell carcinoma,
             non-melanoma skin cancer or curatively resected cervical cancer

          -  Patient has received radiotherapy ≤ 4 weeks or limited field radiation for palliation
             ≤ 2 weeks prior to enrollment, and who has not recovered to grade 1 or better from
             related side effects of such therapy

          -  History of acute pancreatitis within 1 year of screening or past medical history of
             pancreatitis

          -  Patients with central nervous system (CNS) involvement unless they meet ALL of the
             following criteria:

               -  At least 4 weeks from prior therapy completion (including radiation and/or
                  surgery) to starting the study treatment

               -  Clinically stable CNS tumor at the time of screening untreated or without
                  evidence of progressions for at least 4 weeks after treatment as determined by
                  clinical examination and brain imaging (MRI or CT) during screening period and
                  stable low dose of steroids for 2 weeks prior to initiating study treatment

          -  Patient with severe liver impairment (Child Pugh score B/C)

          -  Patient has impairment of gastrointestinal (GI) function or GI disease that may
             significantly alter the absorption of the study drugs

          -  Patient has documented pneumonitis which is active and requiring treatment

          -  Patient has a history of Stevens-Johnson-Syndrome (SJS) or Toxic Epidermal Necroloysis
             (TEN)

          -  Patient is concurrently using other anti-cancer therapy. All anti-cancer therapy must
             be discontinued prior to day one of study treatment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The percentage of patients who are alive without disease progression
Time Frame:Date of first dose to approximately 6 months
Safety Issue:
Description:Assess the percentage of patients without disease progression based on local investigator assessment per RECIST in cohort A, cohort B and cohort C

Secondary Outcome Measures

Measure:Progression free survival (PFS) for each cohort
Time Frame:date of first dose to up to approximately 25 months
Safety Issue:
Description:PFS is defined as the time from the date of first dose of study medication to the date of the first documented progression or death due to any cause occurring in the study. PFS will be assessed based on local investigator's assessment according to RECIST v1.1
Measure:Progression free survival (PFS) on next line treatment PFS2) for each cohort
Time Frame:Date of first dose to date of first documented progression up to approximately 25 months
Safety Issue:
Description:Progression free survival (PFS) on next line treatment (PFS2) is defined as time from the date of first dose of study medication to the date of first documented progression on next-line therapy or death from any cause
Measure:Percentage of participants Overall response rate (ORR) for each cohort
Time Frame:Date of first dose and up to approximately 25 months
Safety Issue:
Description:ORR based on local investigator's assessment according to RECIST v1.1 in each cohort
Measure:Percentage of participants with clinical benefit rate (CBR) for each cohort
Time Frame:Date of first dose and up to approximately 25 months
Safety Issue:
Description:Clinical Benefit Rate (CBR) based on local investigator's assessment according to RECIST v1.1 in each cohort
Measure:Duration of response (DOR)
Time Frame:Date of first documented response to first documented progression or death up to approximately 25 months
Safety Issue:
Description:Duration of Response is the time from the date of first documented response (confirmed CR or PR) to the date of first documented progression or death due to underlying cancer
Measure:Percentable of overall suvivial (OS) for each cohort
Time Frame:Date of first dose and up to approximately 25 months
Safety Issue:
Description:Overall Survival is defined as the time of start of treatment to date of death or lost to follow-up.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • advanced breast cancer
  • PIK3CA
  • CDK 4/6 inhibitor
  • fulvestrant
  • letrozole
  • HR+
  • HER-negative
  • post menopausal
  • pre-menopausal
  • aromatase inhibitor
  • endocrine treatment
  • AI
  • ET

Last Updated

December 30, 2019