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 (EPIK-B3)
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| ClinicalTrials.gov Identifier: NCT04251533 |
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Recruitment Status :
Active, not recruiting
First Posted : February 5, 2020
Last Update Posted : January 13, 2023
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Sponsor:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
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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 (Study Part B1) or PTEN loss without PIK3CA mutation (Study Part B2)
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Triple Negative Breast Neoplasms | Drug: alpelisib Drug: placebo Drug: nab-paclitaxel | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 137 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel 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 16, 2023 |
| Estimated Study Completion Date : | June 19, 2024 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Breast cancer
MedlinePlus related topics:
Breast Cancer
Drug Information available for:
Paclitaxel
| Arm | Intervention/treatment |
|---|---|
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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
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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 |
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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
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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 :
- 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
- 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
- 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 :
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
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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:
- Participant has histologically confirmed diagnosis of advanced (loco-regionally recurrent and not amenable to curative therapy, or metastatic (stage IV)) TNBC
- Participant 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
- Participant 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 B1 - PTEN loss or to Part B2 - PTEN loss without a PIK3CA mutation
- Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Participant has received no more than one line of therapy for metastatic disease.
- Participant has adequate bone marrow and organ function
Exclusion Criteria:
- Participant has received prior treatment with any PI3K, mTOR or AKT inhibitor
- Participant has a known hypersensitivity to alpelisib, nab-paclitaxel or to any of their excipients
- Participant has not recovered from all toxicities related to prior anticancer therapies to NCI CTCAE version 4.03 Grade ≤1; with the exception of alopecia
- Participant has central nervous system (CNS) involvement which was not previously treated and/or was newly detected at screening
- Participant with an established diagnosis of diabetes mellitus type I or uncontrolled type II based on Fasting Plasma Glucose and HbA1c
- Participant 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
- Participant has a history of acute pancreatitis within 1 year prior to screening or past medical history of chronic pancreatitis
- Participant has currently documented pneumonitis/interstitial lung disease
- Participant 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)
- Participant 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
Locations
Show 155 study locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
| Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
| 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: | January 13, 2023 |
| Last Verified: | January 2023 |
| 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 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
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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 |
Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action |