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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 (EPIK-B3)

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ClinicalTrials.gov Identifier: NCT04251533
Recruitment Status : Recruiting
First Posted : February 5, 2020
Last Update Posted : October 19, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
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)

Condition or disease Intervention/treatment Phase
Triple Negative Breast Neoplasms Drug: alpelisib Drug: placebo Drug: nab-paclitaxel Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 566 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : June 8, 2020
Estimated Primary Completion Date : June 19, 2023
Estimated Study Completion Date : November 24, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Paclitaxel

Arm Intervention/treatment
Experimental: alpelisib + nab-paclitaxel
Double-blinded, Randomized in a 1:1 ratio in Study Parts A and B2 Single arm Open label in Study Part B1
Drug: alpelisib
300 mg orally once per day (QD)
Other Name: BYL719

Drug: nab-paclitaxel
100 mg/m² as IV infusion on Days 1, 8 and 15 of a 28-day cycle
Other Name: abraxane

Placebo Comparator: placebo + nab-paclitaxel
Double-blinded, Randomized in a 1:1 ratio in Study Parts A and B2 Not applicable in Study Part B1
Drug: placebo
300 mg orally once per day (QD)
Other Name: alpelisib matching placebo

Drug: nab-paclitaxel
100 mg/m² as IV infusion on Days 1, 8 and 15 of a 28-day cycle
Other Name: abraxane




Primary Outcome Measures :
  1. 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 ]
    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

  2. Progression-free Survival (PFS) Per Investigator Assessment in Study part B2 [ Time Frame: Once approximately 192 PFS events in Study Part B2 had been observed, up to 22 months ]
    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

  3. Overall Response Rate (ORR) based on local radiology assessments in subjects with measurable disease at baseline in study Part B1 [ Time Frame: Up to 6 months ]
    ORR is defined as the proportion of subjects with best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1


Secondary Outcome Measures :
  1. Overall Survival (OS) in Study Part A [ Time Frame: Up to 66 months ]
    OS is defined as the time from date of randomization to date of death due to any cause

  2. Overall Survival (OS) in Study Part B2 [ Time Frame: Up to 41 months ]
    OS is defined as the time from date of randomization to date of death due to any cause

  3. Overall response rate (ORR) with confirmed response in Study Part A [ Time Frame: Up to 35 months ]
    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

  4. Overall response rate (ORR) with confirmed response in Study Part B2 [ Time Frame: Up to 22 months ]
    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

  5. Clinical benefit rate (CBR) with confirmed response in Study Part A [ Time Frame: Up to 35 months ]
    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

  6. Clinical benefit rate (CBR) with confirmed response in Study Part B1 [ Time Frame: Up to 6 months ]
    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

  7. Clinical benefit rate (CBR) with confirmed response in Study Part B2 [ Time Frame: Up to 22 months ]
    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

  8. Time to response (TTR) in Study Part A [ Time Frame: Up to 35 months ]
    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

  9. Time to response (TTR) in Study Part B1 [ Time Frame: Up to 6 months ]
    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

  10. Time to response (TTR) in Study Part B2 [ Time Frame: Up to 22 months ]
    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

  11. Duration of Response (DOR) with confirmed response in Study Part A [ Time Frame: Up to 35 months ]
    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

  12. Duration of Response (DOR) with confirmed response in Study Part B1 [ Time Frame: Up to 6 months ]
    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

  13. Duration of Response (DOR) with confirmed response in Study Part B2 [ Time Frame: Up to 22 months ]
    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

  14. Overall Survival (OS) in Study Part B1 [ Time Frame: Up to 6 months ]
    OS is defined as the time from date of enrolment to date of death due to any cause

  15. Progression-free Survival (PFS) Per Investigator Assessment in Study part B1 [ Time Frame: Up to 6 months ]
    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

  16. Plasma concentrations of alpelisib - Part A [ Time Frame: Up to 35 months ]
    Summary statistics of plasma alpelisib concentrations by time point in study Part A

  17. Plasma concentrations of alpelisib - Part B1 [ Time Frame: Up to 6 months ]
    Summary statistics of plasma alpelisib concentrations by time point in study Part B1

  18. Plasma concentrations of alpelisib -Part B2 [ Time Frame: up to 22 months ]
    Summary statistics of plasma alpelisib concentrations by time point in study Part B2

  19. Plasma concentrations of paclitaxel - Part A [ Time Frame: Up to 35 months ]
    Summary statistics of plasma paclitaxel concentrations by time point in study Part A

  20. Plasma concentrations of paclitaxel - Part B1 [ Time Frame: up to 6 months ]
    Summary statistics of plasma paclitaxel concentrations by time point in study Part B1

  21. 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 ]
    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

  22. 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 ]
    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

  23. 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 ]
    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

  24. 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 ]
    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

  25. 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 ]
    PFS in patients with PIK3CA mutation as measured in ctDNA

  26. 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 ]
    PFS in patients with PIK3CA mutation as measured in ctDNA

  27. 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 ]
    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

  28. Time to definitive deterioration of the ECOG performance status from baseline in Study Part B2 [ Time Frame: Up to 22 months ]
    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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04251533


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04251533    
Other Study ID Numbers: CBYL719H12301
2019-002637-11 ( EudraCT Number )
First Posted: February 5, 2020    Key Record Dates
Last Update Posted: October 19, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

URL: https://www.clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Triple Negative Breast Cancer
alpelisib
BYL719
nab-paclitaxel
PIK3CA mutation
PTEN loss
Additional relevant MeSH terms:
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Triple Negative Breast Neoplasms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action