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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04729387




Registration number
NCT04729387
Ethics application status
Date submitted
25/01/2021
Date registered
28/01/2021

Titles & IDs
Public title
Alpelisib Plus Olaparib in Platinum-resistant/Refractory, High-grade Serous Ovarian Cancer, With no Germline BRCA Mutation Detected
Scientific title
EPIK-O: A Phase III, Multi-center, Randomized (1:1), Open-label, Active-controlled, Study to Assess the Efficacy and Safety of Alpelisib (BYL719) in Combination With Olaparib as Compared to Single Agent Cytotoxic Chemotherapy, in Participants With no Germline BRCA Mutation Detected, Platinum-resistant or Refractory, High-grade Serous Ovarian Cancer
Secondary ID [1] 0 0
2019-004682-40
Secondary ID [2] 0 0
CBYL719K12301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ovarian Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Ovarian and primary peritoneal

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Alpelisib
Treatment: Drugs - Olaparib
Treatment: Drugs - Paclitaxel
Treatment: Drugs - Pegylated liposomal doxorubicin (PLD)

Experimental: Alpelisib+olaparib - Alpelisib 200 mg orally once daily and olaparib 200 mg orally twice daily on a continuous dosing schedule.

Active comparator: Paclitaxel or PLD - Investigator's choice of one of 2 single agent cytotoxic chemotherapies: Paclitaxel 80 mg/m2 intravenously weekly or Pegylated liposomal Doxorubicin (PLD) 40-50 mg/m2 (physician discretion) intravenously every 28 days.


Treatment: Drugs: Alpelisib
Alpelisib will be administered at 200 mg orally once daily following food on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28-day cycle

Treatment: Drugs: Olaparib
Olaparib will be administered at 200 mg orally twice daily irrespective of meals on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28-day cycle.

Treatment: Drugs: Paclitaxel
Paclitaxel will be administered at 80 mg/m2 as an intravenous infusion weekly during a 28-day treatment cycle, starting on Cycle 1 Day 1, and on Day 8, Day 15 and Day 22 of every cycle thereafter

Treatment: Drugs: Pegylated liposomal doxorubicin (PLD)
PLD will be administered at 40-50 mg/m2 (physician discretion) as an intravenous infusion once every 28-days in a 28 day treatment cycle, starting on Cycle 1 Day 1
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS) based on Blinded Independent Review Committee (BIRC) assessment using RECIST 1.1 criteria
Timepoint [1] 0 0
From randomization until the date of the first documented progression or death due to any cause, whichever comes first, assessed up to approximately 23 months
Secondary outcome [1] 0 0
Overall survival
Timepoint [1] 0 0
From randomization until death, assessed up to approximately 44 months
Secondary outcome [2] 0 0
Number of participants with dose interruptions and dose reductions
Timepoint [2] 0 0
From randomization until end of treatment, assessed up to approximately 18 months
Secondary outcome [3] 0 0
Dose intensity
Timepoint [3] 0 0
From randomization until end of treatment, assessed up to approximately 18 months
Secondary outcome [4] 0 0
Time to definitive deterioration of the Eastern Cooperative Oncology Group (ECOG) performance status (PS)
Timepoint [4] 0 0
Up to approximately 18 months
Secondary outcome [5] 0 0
Overall Response Rate (ORR) with confirmed response based on BIRC assessment according to RECIST 1.1 criteria
Timepoint [5] 0 0
Up to approximately 23 months
Secondary outcome [6] 0 0
Clinical benefit rate (CBR) with confirmed response based on BIRC assessment according to RECIST 1.1
Timepoint [6] 0 0
Up to approximately 23 months
Secondary outcome [7] 0 0
Time to response (TTR) based on BIRC assessment and according to RECIST 1.1
Timepoint [7] 0 0
From the date of randomization to the first documented response, assessed up to approximately 23 months
Secondary outcome [8] 0 0
Duration of response (DOR) with confirmed response based on BIRC assessment and according to RECIST 1.1
Timepoint [8] 0 0
From first documented response to first documented progression or death, assessed up to approximately 23 months
Secondary outcome [9] 0 0
Area under the curve calculated to the end of a dosing interval (tau) at steady-state (AUCtau) of alpelisib and olaparib
Timepoint [9] 0 0
Day 8 Cycle 1 (pre-dose, 1, 2, 3, 4, 6, 8 and 24 hours post dose), Day 1 on Cycle 2, 4 and 8 (pre-dose)
Secondary outcome [10] 0 0
Area under the curve from time zero to the last measurable concentration sampling time (AUClast)of alpelisib and olaparib
Timepoint [10] 0 0
Day 8 Cycle 1 (pre-dose, 1, 2, 3, 4, 6, 8 and 24 hours post dose), Day 1 on Cycle 2, 4 and 8 (pre-dose)
Secondary outcome [11] 0 0
Maximum Concentration (Cmax) of alpelisib and olaparib
Timepoint [11] 0 0
Day 8 Cycle 1 (pre-dose, 1, 2, 3, 4, 6, 8 and 24 hours post dose), Day 1 on Cycle 2, 4 and 8 (pre-dose)
Secondary outcome [12] 0 0
Time to reach maximum concentration (Tmax) of alpelisib and olaparib
Timepoint [12] 0 0
Day 8 Cycle 1 (pre-dose, 1, 2, 3, 4, 6, 8 and 24 hours post dose), Day 1 on Cycle 2, 4 and 8 (pre-dose)
Secondary outcome [13] 0 0
Change from baseline in Function Assessment of Cancer Therapy-Ovarian Trial Outcome Index (FACT-O TOI)
Timepoint [13] 0 0
From baseline up to approximately 44 months

Eligibility
Key inclusion criteria
* Participant has histologically confirmed diagnosis of high-grade serous or high-grade endometrioid ovarian cancer, fallopian tube cancer, or primary peritoneal cancer
* Measurable disease, i.e., at least one measurable lesion per RECIST 1.1 criteria (a lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation)
* If no measurable disease is present, the disease should be assessable by Gynecologic Cancer Intergroup criteria (GCIC) for CA-125
* Participant has no germline BRCA1/2 mutation as determined by an FDA approved assay.
* Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Participant has platinum-resistant (progression within one to six months after completing platinum-based therapy) or platinum refractory disease (progression during treatment or within 4 weeks after the last dose), where platinum-based therapy is not an option, according to the GCIG 5th Ovarian Cancer Consensus Conference definitions. The platinum-based chemotherapy regimen does not necessarily need to be the last regimen the participant received prior to study entry.
* Participant must have received at least one but no more than three prior systemic treatment regimens and for whom single-agent chemotherapy is appropriate as the next line of treatment.
* 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 is concurrently using other anti-cancer therapy
* Participant is in a state of small or large bowel obstruction or has other impairment of gastrointestinal (GI) function or GI disease
* Participant has had surgery within 14 days prior to starting study drug or has not recovered from major side effects
* Participant has not recovered from all toxicities 5 related to prior anticancer therapies to baseline or NCI CTCAE Version 4.03 Grade =1. Exception to this criterion: participants with any grade of alopecia are allowed to enter the study.
* Participants with liver impairment and Child Pugh score B or C
* Participant has received radiotherapy = 4 weeks or limited field radiation for palliation =2 weeks prior to randomization, and who has not recovered to baseline, grade 1 or better from related side effects of such therapy (with the exception of alopecia).
* Participant has a known hypersensitivity to any of the study drugs or excipients

Other inclusion/exclusion criteria may 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
Open (masking not used)
Who is / are masked / blinded?



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
2/07/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/01/2026
Actual
Sample size
Target
Accrual to date
Final
358
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Randwick
Recruitment hospital [2] 0 0
Novartis Investigative Site - Bedford Park
Recruitment hospital [3] 0 0
Novartis Investigative Site - Shepparton
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
5041 - Bedford Park
Recruitment postcode(s) [3] 0 0
3630 - Shepparton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
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United States of America
State/province [3] 0 0
Maryland
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
South Dakota
Country [8] 0 0
United States of America
State/province [8] 0 0
Tennessee
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
Argentina
State/province [10] 0 0
Buenos Aires
Country [11] 0 0
Austria
State/province [11] 0 0
Tyrol
Country [12] 0 0
Austria
State/province [12] 0 0
Graz
Country [13] 0 0
Belgium
State/province [13] 0 0
Bruxelles
Country [14] 0 0
Belgium
State/province [14] 0 0
Leuven
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Belgium
State/province [15] 0 0
Namur
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Brazil
State/province [16] 0 0
Minas Gerais
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Brazil
State/province [17] 0 0
SP
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Canada
State/province [18] 0 0
Alberta
Country [19] 0 0
Canada
State/province [19] 0 0
British Columbia
Country [20] 0 0
Canada
State/province [20] 0 0
Ontario
Country [21] 0 0
China
State/province [21] 0 0
Sichuan
Country [22] 0 0
China
State/province [22] 0 0
Beijing
Country [23] 0 0
China
State/province [23] 0 0
Jinan
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China
State/province [24] 0 0
Shanghai
Country [25] 0 0
China
State/province [25] 0 0
Tianjin
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Czechia
State/province [26] 0 0
Czech Republic
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Czechia
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Ostrava Poruba
Country [28] 0 0
Czechia
State/province [28] 0 0
Praha 2
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Denmark
State/province [29] 0 0
Herlev
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Denmark
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Odense C
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Finland
State/province [31] 0 0
Kuopio
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Finland
State/province [32] 0 0
Tampere
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Finland
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Turku
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France
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Besancon
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France
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Lyon
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France
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Paris
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France
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Pierre Benite
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France
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Villejuif
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Germany
State/province [39] 0 0
Baden Wuerttemberg
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Germany
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Berlin
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Germany
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Dresden
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Germany
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Essen
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Italy
State/province [43] 0 0
BO
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Italy
State/province [44] 0 0
FI
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Italy
State/province [45] 0 0
MI
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Italy
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RM
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Italy
State/province [47] 0 0
VI
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Italy
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Napoli
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Korea, Republic of
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Seoul
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Malaysia
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Sabah
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Malaysia
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Sarawak
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Malaysia
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Wilayah Persekutuan
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Malaysia
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Kuala Lumpur
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Mexico
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Nuevo Leon
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Mexico
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Ciudad de Mexico
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Netherlands
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Eindhoven
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Portugal
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Loures
Country [58] 0 0
Portugal
State/province [58] 0 0
Porto
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Russian Federation
State/province [59] 0 0
Arkhangelsk
Country [60] 0 0
Singapore
State/province [60] 0 0
Singapore
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Slovakia
State/province [61] 0 0
Bratislava
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Spain
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Andalucia
Country [63] 0 0
Spain
State/province [63] 0 0
Catalunya
Country [64] 0 0
Spain
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Comunidad Valenciana
Country [65] 0 0
Spain
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Navarra
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Spain
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Madrid
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Taiwan
State/province [67] 0 0
Taichung
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Taiwan
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Taipei
Country [69] 0 0
Turkey
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Adana
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Turkey
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Ankara
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Turkey
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Izmir
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United Kingdom
State/province [72] 0 0
Glasgow
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United Kingdom
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London
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United Kingdom
State/province [74] 0 0
Manchester

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
Address 0 0
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?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04729387