| CTRI Number |
CTRI/2020/09/027887 [Registered on: 18/09/2020] Trial Registered Prospectively |
| Last Modified On: |
26/07/2022 |
| 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
|
|
|
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 = 10 |
| 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 Sandeep Goyle |
Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute |
2nd floor,
Raosaheb Achutrao Patwardhan Marg, four Bunglows, Andheri (W), Mumbai-400053, Maharashtra, India
Mumbai
|
9322527910
sandeep.goyle@kokilabenhospitals.com |
| Dr Rakesh Reddy Boya |
Mahatma Gandhi Cancer Hospital & Research Institute |
Plot No:1, Sector:7, MVP Colony, Visakhapatnam, Andhra Pradesh 530017
Visakhapatnam
|
9013355935
drrakeshreddyboya@yahoo.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= 8 |
| 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-Dr Mohan |
Approved |
| Institutional Review Board (Ethics Committee)-Dr Ashish Singh |
Approved |
| Institutional Review Board- Mahatma Gandhi Cancer Hospital-Dr Rakesh Reddy |
Approved |
| Institutional Review Board-Dr Ganguly |
Approved |
| Mumbai Oncocare Centre Institutional Ethics Committee-Dr Joshi |
Approved |
| nstitutional Ethis Committee-Dr.Goyle |
Approved |
|
Regulatory Clearance Status from DCGI
Modification(s)
|
|
|
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)
|
