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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04251533
Ethics application status
Date submitted
30/01/2020
Date registered
5/02/2020

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
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: Part A: alpelisib + nab-paclitaxel - Participants received alpelisib 300 mg orally + nab-paclitaxel 100 mg/m\^2 intravenously (IV) on Days 1, 8, and 15 of each 28-day cycle

Placebo comparator: Part A: placebo + nab-paclitaxel - Participants received placebo + nab-paclitaxel 100 mg/m\^2 IV on Days 1, 8, and 15 of each 28-day cycle.

Experimental: Part B1: alpelisib + nab-paclitaxel - Participants received alpelisib 300 mg orally + nab-paclitaxel 100 mg/m\^2 IV on Days 1, 8, and 15 of each 28-day cycle.


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

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

Treatment: Drugs: nab-paclitaxel
100 mg/m\^2 IV infusion, once per day (QD)

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
Timepoint [1] 0 0
Once all participants have completed at least 6 months of study treatment or have discontinued from study treatment, up to 35 months
Primary outcome [2] 0 0
Progression-free Survival (PFS) Per Investigator Assessment in Study Part B2
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 Participants With Measurable Disease at Baseline in Study Part B1
Timepoint [3] 0 0
Up to 6 months
Secondary outcome [1] 0 0
Overall Survival in Study Part A
Timepoint [1] 0 0
Up to 66 months
Secondary outcome [2] 0 0
Overall Survival in Study Part B2
Timepoint [2] 0 0
Up to 41 months
Secondary outcome [3] 0 0
Overall Response Rate (ORR) With Confirmed Response in Study Part A
Timepoint [3] 0 0
Once all participants have completed at least 6 months of study treatment or have discontinued from study treatment, up to 35 months
Secondary outcome [4] 0 0
Overall Response Rate (ORR) With Confirmed Response in Study Part B2
Timepoint [4] 0 0
Up to 22 months
Secondary outcome [5] 0 0
Clinical Benefit Rate (CBR) With Confirmed Response in Study Part A
Timepoint [5] 0 0
Once all participants have completed at least 6 months of study treatment or have discontinued from study treatment, up to 35 months
Secondary outcome [6] 0 0
Clinical Benefit Rate (CBR) With Confirmed Response in Study Part B1
Timepoint [6] 0 0
Up to 6 months
Secondary outcome [7] 0 0
Clinical Benefit Rate (CBR) With Confirmed Response in Study Part B2
Timepoint [7] 0 0
Up to 22 months
Secondary outcome [8] 0 0
Time to Response (TTR) in Study Part A
Timepoint [8] 0 0
Once all participants have completed at least 6 months of study treatment or have discontinued from study treatment, up to 35 months
Secondary outcome [9] 0 0
Time to Response (TTR) in Study Part B1
Timepoint [9] 0 0
Up to 6 months
Secondary outcome [10] 0 0
Time to Response (TTR) in Study Part B2
Timepoint [10] 0 0
Up to 22 months
Secondary outcome [11] 0 0
Duration of Response (DOR) With Confirmed Response in Study Part A
Timepoint [11] 0 0
Once all participants have completed at least 6 months of study treatment or have discontinued from study treatment, up to 35 months
Secondary outcome [12] 0 0
Duration of Response (DOR) With Confirmed Response in Study Part B1
Timepoint [12] 0 0
Up to approximately 20 months
Secondary outcome [13] 0 0
Duration of Response (DOR) With Confirmed Response in Study Part B2
Timepoint [13] 0 0
Up to 22 months
Secondary outcome [14] 0 0
Overall Survival in Study Part B1
Timepoint [14] 0 0
Up to approximately 26 months.
Secondary outcome [15] 0 0
Progression-free Survival (PFS) Per Investigator Assessment in Study Part B1
Timepoint [15] 0 0
Up to 6 months
Secondary outcome [16] 0 0
Plasma Concentrations of Alpelisib in Study Part B2
Timepoint [16] 0 0
Up to 22 months
Secondary outcome [17] 0 0
Change From Baseline in the Global Health Status/QoL Scale Score of the EORTC QLQ-C30 in Study Part B2
Timepoint [17] 0 0
Up to 22 months
Secondary outcome [18] 0 0
Time to 10% Definitive Deterioration in the Global Health Status/QOL Scale Score of the EORTC QLQ-C30 in Study Part B2
Timepoint [18] 0 0
Up to 22 months
Secondary outcome [19] 0 0
PFS Based on Local Radiology Assessments Using RECIST 1.1 Criteria for Participants by PIK3CA Mutation Status Measured in Baseline Circulating Tumor Deoxyribonucleic Acid (ctDNA) in Study Part A
Timepoint [19] 0 0
Once all participants have completed at least 6 months of study treatment or have discontinued from study treatment, up to 35 months
Secondary outcome [20] 0 0
PFS Based on Local Radiology Assessments Using RECIST 1.1 Criteria for Participants by PIK3CA Mutation Status Measured in Baseline ctDNA in Study Part B2
Timepoint [20] 0 0
Up to 22 months
Secondary outcome [21] 0 0
Time to Definitive Deterioration of the ECOG Performance Status From Baseline in Study Part B2
Timepoint [21] 0 0
Up to 22 months
Secondary outcome [22] 0 0
Post-Hoc: All Collected Deaths
Timepoint [22] 0 0
On-treatment deaths: Up to approximately 28 months (Part A) or approximately 17 months (Part B1). Post-treatment survival follow-up deaths: Up to approximately 7 additional months (Part A) or approximately 9 additional months (Part B1).

Eligibility
Key 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: Participants 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

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
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not 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)
VIC,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Melbourne
Recruitment hospital [2] 0 0
Novartis Investigative Site - Nedlands
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment postcode(s) [2] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Louisiana
Country [3] 0 0
United States of America
State/province [3] 0 0
Minnesota
Country [4] 0 0
United States of America
State/province [4] 0 0
Tennessee
Country [5] 0 0
Argentina
State/province [5] 0 0
Buenos Aires
Country [6] 0 0
Argentina
State/province [6] 0 0
Santa Fe
Country [7] 0 0
Austria
State/province [7] 0 0
Tyrol
Country [8] 0 0
Austria
State/province [8] 0 0
Leoben
Country [9] 0 0
Brazil
State/province [9] 0 0
SP
Country [10] 0 0
Bulgaria
State/province [10] 0 0
Plovdiv
Country [11] 0 0
China
State/province [11] 0 0
Anhui
Country [12] 0 0
China
State/province [12] 0 0
Hebei
Country [13] 0 0
China
State/province [13] 0 0
Hunan
Country [14] 0 0
China
State/province [14] 0 0
Jiangsu
Country [15] 0 0
China
State/province [15] 0 0
Jilin
Country [16] 0 0
China
State/province [16] 0 0
Liaoning
Country [17] 0 0
China
State/province [17] 0 0
Sichuan
Country [18] 0 0
China
State/province [18] 0 0
Zhejiang
Country [19] 0 0
China
State/province [19] 0 0
Dalian
Country [20] 0 0
China
State/province [20] 0 0
Shanghai
Country [21] 0 0
China
State/province [21] 0 0
Shenyang
Country [22] 0 0
China
State/province [22] 0 0
Tianjin
Country [23] 0 0
Colombia
State/province [23] 0 0
Bogota
Country [24] 0 0
Croatia
State/province [24] 0 0
Zagreb
Country [25] 0 0
France
State/province [25] 0 0
Hauts De Seine
Country [26] 0 0
France
State/province [26] 0 0
Angers Cedex 02
Country [27] 0 0
France
State/province [27] 0 0
Saint-Herblain
Country [28] 0 0
France
State/province [28] 0 0
Villejuif
Country [29] 0 0
Germany
State/province [29] 0 0
Dresden
Country [30] 0 0
Germany
State/province [30] 0 0
Essen
Country [31] 0 0
Germany
State/province [31] 0 0
Leipzig
Country [32] 0 0
Hungary
State/province [32] 0 0
Budapest
Country [33] 0 0
India
State/province [33] 0 0
Haryana
Country [34] 0 0
India
State/province [34] 0 0
Maharashtra
Country [35] 0 0
India
State/province [35] 0 0
Tamil Nadu
Country [36] 0 0
India
State/province [36] 0 0
Telangana
Country [37] 0 0
Israel
State/province [37] 0 0
Tel Aviv
Country [38] 0 0
Italy
State/province [38] 0 0
FC
Country [39] 0 0
Italy
State/province [39] 0 0
RM
Country [40] 0 0
Italy
State/province [40] 0 0
Napoli
Country [41] 0 0
Korea, Republic of
State/province [41] 0 0
Seoul
Country [42] 0 0
Malaysia
State/province [42] 0 0
Selangor
Country [43] 0 0
Malaysia
State/province [43] 0 0
Kuala Lumpur
Country [44] 0 0
Mexico
State/province [44] 0 0
Nuevo Leon
Country [45] 0 0
Norway
State/province [45] 0 0
Oslo
Country [46] 0 0
Peru
State/province [46] 0 0
La Libertad
Country [47] 0 0
Poland
State/province [47] 0 0
Gdynia
Country [48] 0 0
Poland
State/province [48] 0 0
Opole
Country [49] 0 0
Poland
State/province [49] 0 0
Poznan
Country [50] 0 0
Russian Federation
State/province [50] 0 0
Arkhangelsk
Country [51] 0 0
Russian Federation
State/province [51] 0 0
Chelyabinsk
Country [52] 0 0
Russian Federation
State/province [52] 0 0
Moscow
Country [53] 0 0
Russian Federation
State/province [53] 0 0
Pushkin Saint Petersburg
Country [54] 0 0
Slovakia
State/province [54] 0 0
Slovak Republic
Country [55] 0 0
Slovakia
State/province [55] 0 0
Bratislava
Country [56] 0 0
Slovakia
State/province [56] 0 0
Kosice
Country [57] 0 0
Slovenia
State/province [57] 0 0
Ljubljana
Country [58] 0 0
South Africa
State/province [58] 0 0
Western Cape
Country [59] 0 0
South Africa
State/province [59] 0 0
Johannesburg
Country [60] 0 0
Spain
State/province [60] 0 0
Comunidad Valenciana
Country [61] 0 0
Spain
State/province [61] 0 0
Extremadura
Country [62] 0 0
Spain
State/province [62] 0 0
Islas Baleares
Country [63] 0 0
Switzerland
State/province [63] 0 0
Lausanne
Country [64] 0 0
Taiwan
State/province [64] 0 0
Taipei
Country [65] 0 0
Turkey
State/province [65] 0 0
Istanbul
Country [66] 0 0
United Kingdom
State/province [66] 0 0
Nottingham
Country [67] 0 0
United Kingdom
State/province [67] 0 0
Oxford

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.clinicalstudydatarequest.com


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.