Study of Alpelisib (BYL719) in Combination With Trastuzumab and Pertuzumab as Maintenance Therapy in Patients With HER2-positive Advanced Breast Cancer With a PIK3CA Mutation

Official Title

Study of Alpelisib (BYL719) in Combination With Trastuzumab and Pertuzumab as Maintenance Therapy in Patients With HER2-positive Advanced Breast Cancer With a PIK3CA Mutation

Summary:

The purpose of this two part multicenter, randomized, double-blind, placebo-controlled, Phase III study is to evaluate the efficacy and safety of alpelisib compared to alpelisib matching-placebo in combination with trastuzumab and pertuzumab as maintenance treatment of patients with HER2-positive advanced breast cancer whose tumour harbors a PIK3CA mutation following induction therapy with a taxane in combination with trastuzumab and pertuzumab. Part 1 is the open-label, safety run-in part of the study, designed to confirm the recommended phase 3 dose (RP3D) dose of alpelisib in combination with trastuzumab and pertuzumab. Following Part 1, Part 2 will be initiated, which is the randomized, Phase III part of the study.

Trial Description

Primary Outcome Measures :

  • Part 1: Incidence of dose limiting toxicities (DLTs) for each dose level
    • Incidence of DLTs during the first 6 weeks of treatment for each dose level associated with administration of alpelisib in combination with trastuzumab and pertuzumab
  • Part 2: Progression Free Survival (PFS)
    • PFS is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. PFS is based on local investigator assessment and using RECIST 1.1 criteria
Secondary Outcome Measures :
  • Part 1: Alpelisib concentrations by timepoint and dose level
    • Characterize exposure of alpelisib when administered in combination with trastuzumab and pertuzumab
  • Part 2: Overall survival (OS) (Key Secondary)
    • OS is defined as the time from date of randomization to date of death due to any cause
  • Part 2: Summary statistics of alpelisib concentrations by timepoint and dose level
    • Characterize exposure of alpelisib when administered in combination with trastuzumab and pertuzumab
  • Part 2: Overall response rate (ORR) with confirmed response
    • ORR is defined as the percentage 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.
  • Part 2: Clinical Benefit Rate (CBR) with confirmed response
    • Clinical benefit rate is defined as the percentage of patients with a best overall response of complete response (CR) or patial response (PR) or Stable disease (SD) or Non-CR/Non-rogressive disease (PD) lasting more than 24 weeks based on local investigator assessment.
  • Part 2: Time to response (TTR) based on local radiology assessments
    • Time to response (TTR) is defined as the time from the date of randomization to the first documented response of either complete response (CR) or partial response (PR), which must be subsequently confirmed (although date of initial response is used, not date of confirmation). TTR will be assessed using RESIST 1.1 criteria.
  • Part 2: Duration of response (DOR) with confirmed response
    • DOR is calculated as the time from the date of first documented response (complete response (CR) or partial response (PR)) to the first documented date of progression or death due to underlying cancer.
  • Part 2: Change in Functional Assessment of Cancer Therapy - Breast (FACT-B) treatment outcomes index (TOI) from baseline
    • The FACT-B is a 37-item instrument designed to measure five domains of Health-Relaed Quality of Life (HRQOL) in breast cancer patients: Physical Well-being (PWB), Social/family Well-being (SWB), Emotional Well-being (EWB), Functional Well-being (FWB) as well as a Breast Cancer Subscale (BCS).
    • The FACT-B TOI is a composite of PWB, FWB and BCS scores. Total score ranges from 0 to 96. Higher FACT-B TOI scores represent better QoL.
    • Change from baseline in FACT-B TOI scores will be calculated
  • Part 2: Time to deterioration in FACT-B TOI (defined as a ≥ 5 point decrease from baseline)
    • The FACT-B is a 37-item instrument designed to measure five domains of Health-Relaed Quality of Life (HRQOL) in breast cancer patients: Physical Well-being (PWB), Social/family Well-being (SWB), Emotional Well-being (EWB), Functional Well-being (FWB) as well as a Breast Cancer Subscale (BCS).
    • The FACT-B TOI is a composite of PWB, FWB and BCS scores. Total score ranges from 0 to 96. Higher FACT-B TOI scores represent better QoL. Definitive deterioration is defined as the time from the date of randomization to the date of event defined as at least 5-point worsening from baseline with no later improvement above this threshold observed during the course of the treatment or until death due to any cause in FACT-B TOI score
  • Part 2: PFS based on local radiology assessments by PIK3CA mutation status
    • Evaluate the association between PIK3CA mutation status as measured in ctDNA at baseline with PFS upon treatment with alpelisib. PFS will be assessed using RECIST 1.1 criteria for patients by PIK3CA mutation status assessed in ctDNA at baseline.
  • Part 2: Time to definitive deterioration of Eastern Cooperative Group of Oncology Group (ECOG) performance status
    • ECOG: participant's performance status was measured on a 6-point scale: 0= fully active/able to carry on all pre-disease activities without restriction; 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light and sedentary nature; 2= ambulatory and capable of all self-care, but unable to carry out any work activities, up and about more than 50 percent (%) of waking hours; 3= capable of only limited self-care, confined to bed/chair >50% of waking hours; 4= completely disabled, cannot carry on any self-care, totally confined to bed/chair: 5= dead. Time to definitive deterioration in ECOG PS is defined as the time from the date of randomization to the date when the ECOG PS has definitely deteriorated by at least one category compared with baseline. Deterioration is considered definitive if there is no subsequent improvement in ECOG PS back to baseline category or above.

View this trial on ClinicalTrials.gov

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