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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04729387




Registration number
NCT04729387
Ethics application status
Date submitted
25/01/2021
Date registered
28/01/2021
Date last updated
30/05/2024

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
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Arizona
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United States of America
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Florida
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United States of America
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Maryland
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United States of America
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Massachusetts
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United States of America
State/province [5] 0 0
New York
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United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
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South Dakota
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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
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Buenos Aires
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Austria
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Tyrol
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Austria
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Graz
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Belgium
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Bruxelles
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Belgium
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Leuven
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Belgium
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Namur
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Brazil
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Minas Gerais
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Brazil
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SP
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Canada
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Alberta
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Canada
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British Columbia
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Canada
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Ontario
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China
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Sichuan
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China
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Beijing
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China
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Jinan
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China
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Shanghai
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China
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Tianjin
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Czechia
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Czech Republic
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Czechia
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Ostrava Poruba
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Czechia
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Praha 2
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Herlev
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Denmark
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Odense C
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Finland
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Kuopio
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Finland
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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
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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
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BO
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Italy
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FI
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Italy
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MI
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Italy
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RM
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Italy
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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
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Portugal
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Porto
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Russian Federation
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Arkhangelsk
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Singapore
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Singapore
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Slovakia
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Bratislava
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Spain
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Andalucia
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Spain
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Catalunya
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Spain
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Comunidad Valenciana
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Spain
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Navarra
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Spain
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Madrid
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Taiwan
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Taichung
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Taiwan
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Taipei
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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
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Glasgow
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United Kingdom
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London
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United Kingdom
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Manchester

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

Ethics approval
Ethics application status

Summary
Brief summary
The objective of this study is to assess the efficacy and safety of the combination of
alpelisib and olaparib compared with single agent cytotoxic chemotherapy in patients with
platinum resistant or refractory high-grade serous ovarian cancer, with no germline BRCA
mutation detected.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04729387
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04729387