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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04251533




Registration number
NCT04251533
Ethics application status
Date submitted
30/01/2020
Date registered
5/02/2020
Date last updated
19/10/2020

Titles & IDs
Public 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
Scientific 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
Secondary ID [1] 0 0
2019-002637-11
Secondary ID [2] 0 0
CBYL719H12301
Universal Trial Number (UTN)
Trial acronym
EPIK-B3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Triple Negative Breast Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - alpelisib
Treatment: Drugs - placebo
Treatment: Drugs - nab-paclitaxel

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

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


Treatment: Drugs: alpelisib
300 mg orally once per day (QD)

Treatment: Drugs: placebo
300 mg orally once per day (QD)

Treatment: Drugs: nab-paclitaxel
100 mg/m² as IV infusion on Days 1, 8 and 15 of a 28-day cycle

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS) Per Investigator Assessment in Study part A - 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
Timepoint [1] 0 0
Once approximately 192 PFS events in Study Part A had been observed, up to 35 months
Primary outcome [2] 0 0
Progression-free Survival (PFS) Per Investigator Assessment in Study part B2 - 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
Timepoint [2] 0 0
Once approximately 192 PFS events in Study Part B2 had been observed, up to 22 months
Primary outcome [3] 0 0
Overall Response Rate (ORR) based on local radiology assessments in subjects with measurable disease at baseline in study Part B1 - 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
Timepoint [3] 0 0
Up to 6 months
Secondary outcome [1] 0 0
Overall Survival (OS) in Study Part A - OS is defined as the time from date of randomization to date of death due to any cause
Timepoint [1] 0 0
Up to 66 months
Secondary outcome [2] 0 0
Overall Survival (OS) in Study Part B2 - OS is defined as the time from date of randomization to date of death due to any cause
Timepoint [2] 0 0
Up to 41 months
Secondary outcome [3] 0 0
Overall response rate (ORR) with confirmed response in Study Part A - 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
Timepoint [3] 0 0
Up to 35 months
Secondary outcome [4] 0 0
Overall response rate (ORR) with confirmed response in Study Part B2 - 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
Timepoint [4] 0 0
Up to 22 months
Secondary outcome [5] 0 0
Clinical benefit rate (CBR) with confirmed response in Study Part A - 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
Timepoint [5] 0 0
Up to 35 months
Secondary outcome [6] 0 0
Clinical benefit rate (CBR) with confirmed response in Study Part B1 - 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
Timepoint [6] 0 0
Up to 6 months
Secondary outcome [7] 0 0
Clinical benefit rate (CBR) with confirmed response in Study Part B2 - 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
Timepoint [7] 0 0
Up to 22 months
Secondary outcome [8] 0 0
Time to response (TTR) in Study Part A - 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
Timepoint [8] 0 0
Up to 35 months
Secondary outcome [9] 0 0
Time to response (TTR) in Study Part B1 - 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
Timepoint [9] 0 0
Up to 6 months
Secondary outcome [10] 0 0
Time to response (TTR) in Study Part B2 - 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
Timepoint [10] 0 0
Up to 22 months
Secondary outcome [11] 0 0
Duration of Response (DOR) with confirmed response in Study Part A - 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
Timepoint [11] 0 0
Up to 35 months
Secondary outcome [12] 0 0
Duration of Response (DOR) with confirmed response in Study Part B1 - 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
Timepoint [12] 0 0
Up to 6 months
Secondary outcome [13] 0 0
Duration of Response (DOR) with confirmed response in Study Part B2 - 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
Timepoint [13] 0 0
Up to 22 months
Secondary outcome [14] 0 0
Overall Survival (OS) in Study Part B1 - OS is defined as the time from date of enrolment to date of death due to any cause
Timepoint [14] 0 0
Up to 6 months
Secondary outcome [15] 0 0
Progression-free Survival (PFS) Per Investigator Assessment in Study part B1 - 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
Timepoint [15] 0 0
Up to 6 months
Secondary outcome [16] 0 0
Plasma concentrations of alpelisib - Part A - Summary statistics of plasma alpelisib concentrations by time point in study Part A
Timepoint [16] 0 0
Up to 35 months
Secondary outcome [17] 0 0
Plasma concentrations of alpelisib - Part B1 - Summary statistics of plasma alpelisib concentrations by time point in study Part B1
Timepoint [17] 0 0
Up to 6 months
Secondary outcome [18] 0 0
Plasma concentrations of alpelisib -Part B2 - Summary statistics of plasma alpelisib concentrations by time point in study Part B2
Timepoint [18] 0 0
up to 22 months
Secondary outcome [19] 0 0
Plasma concentrations of paclitaxel - Part A - Summary statistics of plasma paclitaxel concentrations by time point in study Part A
Timepoint [19] 0 0
Up to 35 months
Secondary outcome [20] 0 0
Plasma concentrations of paclitaxel - Part B1 - Summary statistics of plasma paclitaxel concentrations by time point in study Part B1
Timepoint [20] 0 0
up to 6 months
Secondary outcome [21] 0 0
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 - 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
Timepoint [21] 0 0
Up to 35 months
Secondary outcome [22] 0 0
Change from baseline in the global health status/QoL scale score of the EORTC QLQ-C30 in study Part B2 - 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
Timepoint [22] 0 0
Up to 22 months
Secondary outcome [23] 0 0
Time to 10% definitive deterioration in the global health status/QOL scale score of the EORTC QLQ-C30 in study Part A - 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
Timepoint [23] 0 0
Up to 35 months
Secondary outcome [24] 0 0
Time to 10% definitive deterioration in the global health status/QOL scale score of the EORTC QLQ-C30 in study Part B2 - 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
Timepoint [24] 0 0
Up to 22 months
Secondary outcome [25] 0 0
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 - PFS in patients with PIK3CA mutation as measured in ctDNA
Timepoint [25] 0 0
Up to 35 months
Secondary outcome [26] 0 0
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 - PFS in patients with PIK3CA mutation as measured in ctDNA
Timepoint [26] 0 0
Up to 22 months
Secondary outcome [27] 0 0
Time to definitive deterioration of the Eastern Cooperative Oncology Group (ECOG) performance status (PS) from baseline in Study Part A - 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
Timepoint [27] 0 0
Up to 35 months
Secondary outcome [28] 0 0
Time to definitive deterioration of the ECOG performance status from baseline in Study Part B2 - 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
Timepoint [28] 0 0
Up to 22 months

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Factorial
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Murdoch
Recruitment hospital [2] 0 0
Novartis Investigative Site - Nedlands
Recruitment postcode(s) [1] 0 0
6150 - Murdoch
Recruitment postcode(s) [2] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Nevada
Country [2] 0 0
United States of America
State/province [2] 0 0
Ohio
Country [3] 0 0
United States of America
State/province [3] 0 0
Texas
Country [4] 0 0
Brazil
State/province [4] 0 0
SP
Country [5] 0 0
France
State/province [5] 0 0
Angers Cedex 02
Country [6] 0 0
France
State/province [6] 0 0
Besancon Cedex
Country [7] 0 0
France
State/province [7] 0 0
Clermont-Ferrand
Country [8] 0 0
France
State/province [8] 0 0
Creteil
Country [9] 0 0
France
State/province [9] 0 0
Metz
Country [10] 0 0
France
State/province [10] 0 0
Paris Cedex 10
Country [11] 0 0
France
State/province [11] 0 0
Poitiers
Country [12] 0 0
France
State/province [12] 0 0
Reims
Country [13] 0 0
France
State/province [13] 0 0
Saint-Herblain Cédex
Country [14] 0 0
Germany
State/province [14] 0 0
Baden-Wuerttemberg
Country [15] 0 0
Germany
State/province [15] 0 0
Bavaria
Country [16] 0 0
Germany
State/province [16] 0 0
North Rhine-westphalia
Country [17] 0 0
Germany
State/province [17] 0 0
Erlangen
Country [18] 0 0
Germany
State/province [18] 0 0
Leipzig
Country [19] 0 0
Germany
State/province [19] 0 0
Tübingen
Country [20] 0 0
Hungary
State/province [20] 0 0
Debrecen
Country [21] 0 0
Hungary
State/province [21] 0 0
Kecskemet
Country [22] 0 0
Hungary
State/province [22] 0 0
Tatabanya
Country [23] 0 0
Israel
State/province [23] 0 0
Be'er Sheva
Country [24] 0 0
Israel
State/province [24] 0 0
Tel Aviv
Country [25] 0 0
Italy
State/province [25] 0 0
ME
Country [26] 0 0
Italy
State/province [26] 0 0
RM
Country [27] 0 0
Malaysia
State/province [27] 0 0
Selangor
Country [28] 0 0
Malaysia
State/province [28] 0 0
Kuala Lumpur
Country [29] 0 0
Norway
State/province [29] 0 0
Oslo
Country [30] 0 0
Norway
State/province [30] 0 0
Stavanger
Country [31] 0 0
Russian Federation
State/province [31] 0 0
Arkhangelsk
Country [32] 0 0
Russian Federation
State/province [32] 0 0
Chelyabinsk
Country [33] 0 0
Russian Federation
State/province [33] 0 0
Moscow
Country [34] 0 0
Russian Federation
State/province [34] 0 0
Pushkin Saint Petersburg
Country [35] 0 0
Slovakia
State/province [35] 0 0
Bratislava
Country [36] 0 0
Slovakia
State/province [36] 0 0
Kosice
Country [37] 0 0
Spain
State/province [37] 0 0
Madrid
Country [38] 0 0
Switzerland
State/province [38] 0 0
Aarau
Country [39] 0 0
Switzerland
State/province [39] 0 0
Zurich
Country [40] 0 0
Taiwan
State/province [40] 0 0
Taichung
Country [41] 0 0
Taiwan
State/province [41] 0 0
Taipei
Country [42] 0 0
United Kingdom
State/province [42] 0 0
Nottingham

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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)
Trial website
https://clinicaltrials.gov/show/NCT04251533
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
1-888-669-6682
Fax 0 0
Email 0 0
novartis.email@novartis.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04251533