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: Efficacy and Safety of Treatment With Alpelisib Plus Endocrine Therapy in Patients With HR+, HER2-negative aBC, With PIK3CA Mutations, Whose Disease Has Progressed on or After CDK 4/6 Treatment With an Aromatase Inhibitor (AI) or Fulvestrant
  • Official Title: A Phase II, Multicenter, Open-label, Two-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 CDK 4/6 Inhibitor Treatment

Clinical Trial IDs

  • ORG STUDY ID: CBYL719X2402
  • NCT ID: NCT03056755

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
alpelisibBYL719alpelisib + fulvestrant
fulvestrantalpelisib + fulvestrant
letrozolealpelisib + letrozole

Purpose

Efficacy and safety of treatment with alpelisib plus endocrine therapy in patients with HR+, HER2-negative aBC, with PIK3CA mutations, whose disease has progressed on or after CDK 4/6 treatment with an aromatase inhibitor (AI) or fulvestrant

Trial Arms

NameTypeDescriptionInterventions
alpelisib + fulvestrantExperimentalPatients who received any CDK 4/6 inhibitor plus aromatase inhibitor as treatment (immediately prior) will receive alpelisib + fulvestrant
  • alpelisib
  • fulvestrant
alpelisib + letrozoleExperimentalPatients who received any CDK 4/6 inhibitor plus fulvestrant as treatment (immediately prior) will receive alpelisib + letrozole
  • alpelisib
  • letrozole

Eligibility Criteria

        Inclusion Criteria:

          -  patient is male or female 18 years or older

          -  Patient is identified PIK3CA mutant status

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

          -  Patient must be diagnosed with aBC with documented progression on or after CDK 4/6
             treatment (adjuvant or metastatic setting)

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

          -  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 adequate bone marrow function

          -  Patient has adequate liver and renal function

        Exclusion Criteria:

          -  patient has received prior treatment with any PI3K inhibitors

          -  patient with clinically manifest diabetes mellitus, or documented steroid induced
             diabetes mellitus

          -  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

          -  Bilateral diffuse lymphangitis carcinomatosis

          -  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
      
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 and cohort B

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 is defined as the percentage of participants with best overall response (BOR) of CR or partial response (PR), as per local investigator's assessment and according to RECIST v1.1.
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:CBR is defined as the percentage of participants with a best ORR of complete response (CR) or partial response (PR) or an overall lesion response of stable disease (SD) or Non-CR/ Non-PD lasting ≥ 24 weeks based on local investigator's assessment according to RECIST v1.1
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

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

Last Updated

June 16, 2017