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CTRI Number  CTRI/2020/09/027887 [Registered on: 18/09/2020] Trial Registered Prospectively
Last Modified On: 06/04/2021
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study
Modification(s)  
Drug 
Study Design  Randomized, Parallel Group, Placebo Controlled Trial 
Public Title of Study
Modification(s)  
Study Assessing the Efficacy and Safety of Alpelisib in combination with Nab-paclitaxel in Subjects With Advanced TNBC Who Carry Either a PIK3CA Mutation or Have PTEN Loss Without PIK3CA Mutation  
Scientific Title of Study   EPIK-B3: 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 IDs if Any
Modification(s)  
Secondary ID  Registry 
NCT04251533  ClinicalTrials.gov 
2019-002637-11  EudraCT 
CBYL719H12301 ,V 00,dated 26-Nov-2019  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Modification(s)  
Name  Murugananthan K 
Address  Novartis Healthcare Pvt Ltd GDO Trial Monitoring, India 6 & 7 floor , Inspire BKC G Block, BKC Main Road Bandra Kurla Complex Bandra (East

Mumbai
MAHARASHTRA
400051
India 
Phone    
Fax    
Email  murugananthan.k@novartis.com  
 
Details Contact Person
Scientific Query

Modification(s)  
Name  Murugananthan K 
Address  Novartis Healthcare Pvt Ltd GDO Trial Monitoring, India 6 & 7 floor , Inspire BKC G Block, BKC Main Road Bandra Kurla Complex Bandra (East

Mumbai
MAHARASHTRA
400051
India 
Phone    
Fax    
Email  murugananthan.k@novartis.com  
 
Details Contact Person
Public Query

Modification(s)  
Name  Murugananthan K 
Address  Novartis Healthcare Pvt Ltd GDO Trial Monitoring, India 6 & 7 floor , Inspire BKC G Block, BKC Main Road Bandra Kurla Complex Bandra (East

Mumbai
MAHARASHTRA
400051
India 
Phone    
Fax    
Email  murugananthan.k@novartis.com  
 
Source of Monetary or Material Support  
Novartis Pharma AG, Novartis Campus 4056 – Basel, Switzerland 
 
Primary Sponsor  
Name  Novartis Healthcare Pvt Ltd 
Address  Novartis Healthcare Pvt Ltd GDO Trial Monitoring, India 6 & 7 floor , Inspire BKC G Block, BKC Main Road Bandra Kurla Complex Bandra (East), Mumbai – 400051 India 
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NA 
 
Countries of Recruitment     Argentina
Australia
Austria
Brazil
Bulgaria
Canada
China
Colombia
Croatia
Democratic People's Republic of Korea
France
Germany
Hungary
India
Israel
Italy
Kenya
Malaysia
Mexico
Norway
Poland
Romania
Russian Federation
Saudi Arabia
Serbia
Slovakia
Slovenia
South Africa
Spain
Switzerland
Taiwan
United Kingdom
United States of America  
Sites of Study
Modification(s)  
No of Sites = 9  
Contact Person  Name of Site  Site Address  Phone/Fax/Email 
Dr T Raja  Apollo Speciality Hospital  Department of Medical Oncology, No 320, Padma Complex, Anna Salai, chennai-600035
Chennai
 
9841070195

rajatraj@yahoo.com 
Dr Prashant Mehta  Asian Institute of Medical Sciences,  room no 149, Badkal Flyover, Road, Sector 21A, Faridabad, Haryana 121001, India
Faridabad
 
9599460474

prashantcipher7@gmail.com 
Dr M V T Krishna Mohan  Basavatarakam Indo American Cancer Hospital & Research Institute,  Rd Number 10, Banjara Hills, Hyderabad-500034, Telangana, india
Hyderabad
 
9866154503

krishna.mvt@gmail.com 
Dr Ashish Singh  Christian Medical College  Department of Medical Oncology, Ida Scudder Road, Vellore - 632004, Tamil Nadu, India
Vellore
 
9445659460

todrashish@gmail.com 
Dr Sewanti Atul Limaye  Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute  2nd floor, Raosaheb Achutrao Patwardhan Marg, four Bunglows, Andheri (W), Mumbai-400053, Maharashtra, India
Mumbai
 
9619607339

sewanti.limaye@relianceada.com 
Dr Vaibhav Choudhary  Meditrina Institute of Medical Sciences  Room no 09, 1st floor, 278, Central Bazar Road, Ramdaspeth, Nagpur-440010
Nagpur
 
9833621049

dr.vaibhav155@gmail.com 
Dr Ashish Joshi  Mumbai Oncocare Centre (Unit of Cellcure Cancer Centre Pvt Ltd)  2nd Floor, Majithia Apartments, God’s Gift Premises co-op Soc Ltd, S V Road, Vile Parle  ( W), Mumbai- 400 056
Mumbai
 
9920767626

ashjoshi44@mocindia.co.in 
Dr Sandip Ganguly  Tata Medical Centre  14 major Arterial Road (EW), New Town, Rajarhat, Kolkata-700160
Kolkata
 
9663667459

sandip.ganguly@tmckolkata.com 
Dr Nikhil S Ghadyalpatil  Yashoda Hospital  Department of Medical Oncology, Raj Bhavan Roa, Somajiguda, Hyderabad-500 082,Telanagana,India
Hyderabad
 
8008307474

nikhilghadyalpatil@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 9  
Name of Committee  Approval Status 
Ethics Commttee, Asian Institute of Medical Sciences--Dr, Prashant Mehta  Approved 
Institutional Ethics Committee, Yashoda Academy of Medical Education and Research-Dr -Nikhil S Ghadyalpatil  Approved 
Institutional Ethics Committee-clinical Studies-Dr. Raja Thirumalairaj  Submittted/Under Review 
Institutional Ethics Committee-Dr Mohan  Approved 
Institutional Review Board (Ethics Committee)-Dr Ashish Singh  Approved 
Institutional Review Board-Dr Ganguly  Approved 
Meditrina institute of Ethics Committee-Dr. Vaibhav Choudhary  Submittted/Under Review 
Mumbai Oncocare Centre Institutional Ethics Committee-Dr Joshi  Approved 
nstitutional Ethis Committee-Dr.Limaye  Approved 
 
Regulatory Clearance Status from DCGI
Modification(s)  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  Malignant neoplasm of breast of unspecified site 
Patients  Malignant neoplasm of connective and soft tissue, unspecified 
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Drug: alpelisib  300 mg orally once per day (QD) 
Intervention  nab-paclitaxel   100 mg/m² as IV infusion on Days 1, 8 and 15 of a 28-day cycle 
Comparator Agent  nab-paclitaxel  100 mg/m² as IV infusion on Days 1, 8 and 15 of a 28-day cycle 
Comparator Agent  placebo   300 mg orally once per day (QD) 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  99.00 Year(s)
Gender  Both 
Details  1.Subject is ≥ 18 years old at the time of informed consent
2.Subject has histologically confirmed diagnosis of advanced (loco-regionally recurrent and not amenable to curative therapy, or metastatic (stage IV)) TNBC
3.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
4.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 5.subject can be allocated to Part A - PIK3CA mutation regardless of PTEN status; or to Part B - PTEN loss without a PIK3CA mutation
6.Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
7.Subject has received no more than one line of therapy for metastatic disease.
8.Subject has adequate bone marrow and organ function
 
 
ExclusionCriteria 
Details  1.Subject has received prior treatment with any PI3K, mTOR or AKT inhibitor
2.Subject has a known hypersensitivity to alpelisib, nab-paclitaxel or to any of their excipients
3.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
4.Subject has central nervous system involvement
5.Subject with an established diagnosis of diabetes mellitus type I or uncontrolled type II based on Fasting Plasma Glucose and HbA1c
6.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
7.Subject has a history of acute pancreatitis within 1 year of screening or past medical history of chronic pancreatitis
8.Subject has currently documented pneumonitis/interstitial lung disease
9.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)
10.Subject with unresolved osteonecrosis of the jaw

 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Participant and Investigator Blinded 
Primary Outcome
Modification(s)  
Outcome  TimePoints 
1-Progression-free Survival (PFS) Per Investigator Assessment in Study part A
2-Progression-free Survival (PFS) Per Investigator Assessment in Study part B2
3-Overall Response Rate (ORR) based on local radiology assessments in subjects with measurable disease at baseline in study Part B1  
1-Once approximately 192 PFS events in Study Part A had been observed, up to 35 months
2-Time Frame: Once approximately 192 PFS events in Study Part B2 had been observed, up to 22 months
3-Time Frame: Up to 6 months  
 
Secondary Outcome  
Outcome  TimePoints 
Change from baseline in the global health status/QoL scale score of the EORTC QLQ-C30 in study Part A  35 months  
Change from baseline in the global health status/QoL scale score of the EORTC QLQ-C30 in study Part B2   Up to 22 months 
Clinical benefit rate (CBR) with confirmed response in Study Part A  Up to 35 months 
Clinical benefit rate (CBR) with confirmed response in Study Part B1   Up to 6 months 
Clinical benefit rate (CBR) with confirmed response in Study Part B2   Up to 22 months  
Duration of Response (DOR) with confirmed response in Study Part A  Up to 35 months 
Duration of Response (DOR) with confirmed response in Study Part B1   Up to 6 months  
Duration of Response (DOR) with confirmed response in Study Part B2   Up to 22 months 
Overall response rate (ORR) with confirmed response in Study Part A  Up to 35 months  
Overall response rate (ORR) with confirmed response in Study Part B2   Up to 22 months  
Overall Survival (OS) in Study Part A  Up to 66 months  
Overall Survival (OS) in Study Part B1   Up to 6 months  
Overall Survival (OS) in Study Part B2   Up to 41 months  
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  Up to 35 months 
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   Up to 22 months 
Plasma concentrations of alpelisib - Part A  Up to 35 months  
Plasma concentrations of alpelisib - Part B1   Time Frame: Up to 6 months  
Plasma concentrations of alpelisib -Part B2   up to 22 months  
Plasma concentrations of paclitaxel - Part A  Up to 35 months  
Plasma concentrations of paclitaxel - Part B  up to 6 months  
Progression-free Survival (PFS) Per Investigator Assessment in Study part B1   Up to 6 months  
Time to 10% definitive deterioration in the global health status/QOL scale score of the EORTC QLQ-C30 in study Part A  Up to 35 months  
Time to 10% definitive deterioration in the global health status/QOL scale score of the EORTC QLQ-C30 in study Part B2  Up to 22 months  
Time to definitive deterioration of the ECOG performance status from baseline in Study Part A  Up to 35 months  
Time to definitive deterioration of the ECOG performance status from baseline in Study Part B2   Up to 22 months 
Time to response (TTR) in Study Part A  Up to 35 months  
Time to response (TTR) in Study Part B1   Up to 6 months  
Time to response (TTR) in Study Part B2   Up to 22 months  
 
Target Sample Size   Total Sample Size="540"
Sample Size from India="20" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)
Modification(s)  
25/09/2020 
Date of First Enrollment (Global)  08/06/2020 
Estimated Duration of Trial   Years="6"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Open to Recruitment 
Recruitment Status of Trial (India)  Open to Recruitment 
Publication Details
Modification(s)  
NIL 
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)
 

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