Clinical Trials /

Study Assessing the Efficacy and Safety of Alpelisib + Nab-paclitaxel in Subjects With Advanced TNBC Who Carry Either a PIK3CA Mutation or Have PTEN Loss Without PIK3CA Mutation

NCT04251533

Description:

The purpose of this study is to determine whether treatment with alpelisib in combination with nab-paclitaxel is safe and effective in subjects with advanced triple negative breast cancer (aTNBC) who carry either a PIK3CA mutation (Study Part A) or have PTEN loss without PIK3CA mutation (Study Parts B1 and B2)

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study Assessing the Efficacy and Safety of Alpelisib + Nab-paclitaxel in Subjects With Advanced TNBC Who Carry Either a PIK3CA Mutation or Have PTEN Loss Without PIK3CA Mutation
  • Official Title: A Phase III, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Alpelisib (BYL719) in Combination With Nab-paclitaxel in Patients With Advanced Triple Negative Breast Cancer With Either Phosphoinositide-3-kinase Catalytic Subunit Alpha (PIK3CA) Mutation or Phosphatase and Tensin Homolog Protein (PTEN) Loss Without PIK3CA Mutation

Clinical Trial IDs

  • ORG STUDY ID: CBYL719H12301
  • SECONDARY ID: 2019-002637-11
  • NCT ID: NCT04251533

Conditions

  • Triple Negative Breast Neoplasms

Interventions

DrugSynonymsArms
alpelisibBYL719alpelisib + nab-paclitaxel
placeboalpelisib matching placeboplacebo + nab-paclitaxel
nab-paclitaxelabraxanealpelisib + nab-paclitaxel

Purpose

The purpose of this study is to determine whether treatment with alpelisib in combination with nab-paclitaxel is safe and effective in subjects with advanced triple negative breast cancer (aTNBC) who carry either a PIK3CA mutation (Study Part A) or have PTEN loss without PIK3CA mutation (Study Parts B1 and B2)

Trial Arms

NameTypeDescriptionInterventions
alpelisib + nab-paclitaxelExperimentalDouble-blinded, Randomized in a 1:1 ratio in Study Parts A and B2 Single arm Open label in Study Part B1
  • alpelisib
  • nab-paclitaxel
placebo + nab-paclitaxelPlacebo ComparatorDouble-blinded, Randomized in a 1:1 ratio in Study Parts A and B2 Not applicable in Study Part B1
  • placebo
  • nab-paclitaxel

Eligibility Criteria

        Inclusion Criteria:

          -  Subject has histologically confirmed diagnosis of advanced (loco-regionally recurrent
             and not amenable to curative therapy, or metastatic (stage IV)) TNBC

          -  Subject has either a measurable disease per RECIST 1.1 criteria or, if no measurable
             disease is present, then at least one predominantly lytic bone lesion or mixed
             lytic-blastic bone lesion with identifiable soft tissue component (that can be
             evaluated by CT/MRI) must be present Part B1: patients must have measurable disease

          -  Subject has adequate tumor tissue to identify the PIK3CA mutation status (either
             carrying a mutation or without a mutation) and the PTEN loss status; both of which
             will determine whether the subject can be allocated to Part A - PIK3CA mutation
             regardless of PTEN status; or to Part B - PTEN loss without a PIK3CA mutation

          -  Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Subject has received no more than one line of therapy for metastatic disease.

          -  Subject has adequate bone marrow and organ function

        Exclusion Criteria:

          -  Subject has received prior treatment with any PI3K, mTOR or AKT inhibitor

          -  Subject has a known hypersensitivity to alpelisib, nab-paclitaxel or to any of their
             excipients

          -  Subject has not recovered from all toxicities related to prior anticancer therapies to
             NCI CTCAE version 4.03 Grade ≤1; with the exception of alopecia

          -  Subject has central nervous system (CNS) involvement

          -  Subject with an established diagnosis of diabetes mellitus type I or uncontrolled type
             II based on Fasting Plasma Glucose and HbA1c

          -  Subject has impairment of gastrointestinal (GI) function or GI disease that may
             significantly alter the absorption of the study drugs (e.g., ulcerative diseases,
             uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel
             resection) based on investigator discretion

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

          -  Subject has currently documented pneumonitis/interstitial lung disease

          -  Subject has a history of severe cutaneous reactions, such as Steven-Johnson Syndrome
             (SJS), erythema multiforme (EM),Toxic Epidermal Necrolysis (TEN) or Drug Reaction with
             Eosinophilia and Systemic Syndrome (DRESS)

          -  Subject with unresolved osteonecrosis of the jaw

        Other protocol-defined inclusion/exclusion criteria 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 Study part A
Time Frame:Once approximately 192 PFS events in Study Part A had been observed, up to 35 months
Safety Issue:
Description:PFS, defined as 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) in Study Part A
Time Frame:Up to 66 months
Safety Issue:
Description:OS is defined as the time from date of randomization to date of death due to any cause
Measure:Overall Survival (OS) in Study Part B2
Time Frame:Up to 41 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) with confirmed response in Study Part A
Time Frame:Up to 35 months
Safety Issue:
Description:ORR with confirmed response is the proportion of subjects with BOR of confirmed complete response (CR) or confirmed partial response (PR), as per local review and according to RECIST 1.1
Measure:Overall response rate (ORR) with confirmed response in Study Part B2
Time Frame:Up to 22 months
Safety Issue:
Description:ORR with confirmed response is the proportion of subjects with BOR of confirmed complete response (CR) or confirmed partial response (PR), as per local review and according to RECIST 1.1
Measure:Clinical benefit rate (CBR) with confirmed response in Study Part A
Time Frame:Up to 35 months
Safety Issue:
Description:Clinical benefit rate (CBR) with confirmed response is defined as the proportion of subjects with a best overall response of confirmed complete response (CR), or confirmed partial response (PR), or an overall response of stable disease (SD) lasting for a duration of at least 24 weeks. CR, PR, and SD are defined as per local review according to RECIST 1.1
Measure:Clinical benefit rate (CBR) with confirmed response in Study Part B1
Time Frame:Up to 6 months
Safety Issue:
Description:Clinical benefit rate (CBR) with confirmed response is defined as the proportion of subjects with a best overall response of confirmed complete response (CR), or confirmed partial response (PR), or an overall response of stable disease (SD) lasting for a duration of at least 24 weeks. CR, PR, and SD are defined as per local review according to RECIST 1.1
Measure:Clinical benefit rate (CBR) with confirmed response in Study Part B2
Time Frame:Up to 22 months
Safety Issue:
Description:Clinical benefit rate (CBR) with confirmed response is defined as the proportion of subjects with a best overall response of confirmed complete response (CR), or confirmed partial response (PR), or an overall response of stable disease (SD) lasting for a duration of at least 24 weeks. CR, PR, and SD are defined as per local review according to RECIST 1.1
Measure:Time to response (TTR) in Study Part A
Time Frame:Up to 35 months
Safety Issue:
Description:Time to response (TTR) is defined as the time from the date of randomization/enrolment 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). CR and PR are based on tumor response data as per local review and according to RECIST 1.1
Measure:Time to response (TTR) in Study Part B1
Time Frame:Up to 6 months
Safety Issue:
Description:Time to response (TTR) is defined as the time from the date of randomization/enrolment 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). CR and PR are based on tumor response data as per local review and according to RECIST 1.1
Measure:Time to response (TTR) in Study Part B2
Time Frame:Up to 22 months
Safety Issue:
Description:Time to response (TTR) is defined as the time from the date of randomization/enrolment 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). CR and PR are based on tumor response data as per local review and according to RECIST 1.1
Measure:Duration of Response (DOR) with confirmed response in Study Part A
Time Frame:Up to 35 months
Safety Issue:
Description:Duration of response (DOR) with confirmed response only applies to subjects whose best overall response is confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1 based on tumor response data per local review. The start date is the date of first documented response of CR or PR (i.e. the start date of response, not the date when response was confirmed), and the end date is defined as the date of the first documented progression or death due to underlying cancer
Measure:Duration of Response (DOR) with confirmed response in Study Part B1
Time Frame:Up to 6 months
Safety Issue:
Description:Duration of response (DOR) with confirmed response only applies to subjects whose best overall response is confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1 based on tumor response data per local review. The start date is the date of first documented response of CR or PR (i.e. the start date of response, not the date when response was confirmed), and the end date is defined as the date of the first documented progression or death due to underlying cancer
Measure:Duration of Response (DOR) with confirmed response in Study Part B2
Time Frame:Up to 22 months
Safety Issue:
Description:Duration of response (DOR) with confirmed response only applies to subjects whose best overall response is confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1 based on tumor response data per local review. The start date is the date of first documented response of CR or PR (i.e. the start date of response, not the date when response was confirmed), and the end date is defined as the date of the first documented progression or death due to underlying cancer
Measure:Overall Survival (OS) in Study Part B1
Time Frame:Up to 6 months
Safety Issue:
Description:OS is defined as the time from date of enrolment to date of death due to any cause
Measure:Progression-free Survival (PFS) Per Investigator Assessment in Study part B1
Time Frame:Up to 6 months
Safety Issue:
Description:PFS, defined as time from the date of enrolment 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
Measure:Plasma concentrations of alpelisib - Part A
Time Frame:Up to 35 months
Safety Issue:
Description:Summary statistics of plasma alpelisib concentrations by time point in study Part A
Measure:Plasma concentrations of alpelisib - Part B1
Time Frame:Up to 6 months
Safety Issue:
Description:Summary statistics of plasma alpelisib concentrations by time point in study Part B1
Measure:Plasma concentrations of alpelisib -Part B2
Time Frame:up to 22 months
Safety Issue:
Description:Summary statistics of plasma alpelisib concentrations by time point in study Part B2
Measure:Plasma concentrations of paclitaxel - Part A
Time Frame:Up to 35 months
Safety Issue:
Description:Summary statistics of plasma paclitaxel concentrations by time point in study Part A
Measure:Plasma concentrations of paclitaxel - Part B1
Time Frame:up to 6 months
Safety Issue:
Description:Summary statistics of plasma paclitaxel concentrations by time point in study Part B1
Measure:Change from baseline in the global health status/Quality of life (QoL) scale score of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-item Core Module (EORTC QLQ-C30) in study Part A
Time Frame:Up to 35 months
Safety Issue:
Description:Summary of composite measure of change from baseline in the domain scores, health states, overall health status, and index values at the time of each assessment
Measure:Change from baseline in the global health status/QoL scale score of the EORTC QLQ-C30 in study Part B2
Time Frame:Up to 22 months
Safety Issue:
Description:Summary of composite measure of change from baseline in the domain scores, health states, overall health status, and index values at the time of each assessment
Measure:Time to 10% definitive deterioration in the global health status/QOL scale score of the EORTC QLQ-C30 in study Part A
Time Frame:Up to 35 months
Safety Issue:
Description:Definitive deterioration: time from date of randomization to date of event, defined as at least a 10% 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 the global health status/QOL scale score of EORTC QLQ-C30, a questionnaire to assess the quality of life of cancer patients. The questionnaire contains 30 items & is composed of both multi-item scales & single-item measures based on the patient's experience over the past week. This includes 5 functional scales, 3 symptom scales, 6 single items & a global health status/QoL scale. The scales & single-item measures range in score from 0 - 100. A high scale score represents a higher response level. A high score for a functional scale represents a high/healthy level of functioning; a high score for the global health status/QoL represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problems
Measure:Time to 10% definitive deterioration in the global health status/QOL scale score of the EORTC QLQ-C30 in study Part B2
Time Frame:Up to 22 months
Safety Issue:
Description:Definitive deterioration: time from date of randomization to date of event, defined as at least a 10% 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 the global health status/QOL scale score of EORTC QLQ-C30, a questionnaire to assess the quality of life of cancer patients. The questionnaire contains 30 items & is composed of both multi-item scales & single-item measures based on the patient's experience over the past week. This includes 5 functional scales, 3 symptom scales, 6 single items & a global health status/QoL scale. The scales & single-item measures range in score from 0 - 100. A high scale score represents a higher response level. A high score for a functional scale represents a high/healthy level of functioning; a high score for the global health status/QoL represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problems
Measure:PFS based on local radiology assessments using RECIST 1.1 criteria for subjects by PIK3CA mutation status measured in baseline ctDNA in study Part A
Time Frame:Up to 35 months
Safety Issue:
Description:PFS in patients with PIK3CA mutation as measured in ctDNA
Measure:PFS based on local radiology assessments using RECIST 1.1 criteria for subjects by PIK3CA mutation status measured in baseline ctDNA in study Part B2
Time Frame:Up to 22 months
Safety Issue:
Description:PFS in patients with PIK3CA mutation as measured in ctDNA
Measure:Time to definitive deterioration of the Eastern Cooperative Oncology Group (ECOG) performance status (PS) from baseline in Study Part A
Time Frame:Up to 35 months
Safety Issue:
Description:Definitive deterioration of ECOG PS is defined as the time from the date of randomization to the date of event defined as a worsening of at least once category from baseline in ECOG PS with no later improvement above this threshold observed during the course of the treatment or until death due to any cause
Measure:Time to definitive deterioration of the ECOG performance status from baseline in Study Part B2
Time Frame:Up to 22 months
Safety Issue:
Description:Definitive deterioration of ECOG PS is defined as the time from the date of randomization to the date of event defined as a worsening of at least once category from baseline in ECOG PS with no later improvement above this threshold observed during the course of the treatment or until death due to any cause

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • Triple Negative Breast Cancer
  • alpelisib
  • BYL719
  • nab-paclitaxel
  • PIK3CA mutation
  • PTEN loss

Last Updated

September 21, 2020