Alpelisib Plus Olaparib in Platinum-resistant/Refractory, High-grade Serous Ovarian Cancer, With no Germline BRCA Mutation Detected

NCT ID: NCT04729387

Last Updated: 2025-10-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

358 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-07-22

Study Completion Date

2025-12-05

Brief Summary

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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.

Detailed Description

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This study will include adult women with platinum resistant or refractory high-grade serous ovarian cancer, with no germline BRCA mutation detected. Participants will be randomized in a 1:1 ratio to either alpelisib plus olaparib or single agent cytotoxic chemotherapy (paclitaxel or PLD) in this open-label, active controlled study.

Participants will continue to receive study treatment until disease progression, unacceptable toxicity that precludes further treatment, or until discontinuation of study treatment due to any other reason. After treatment discontinuation, all participants will enter in the post-treatment follow-up period, which consists of a safety follow-up visit and a 9-week post-progression visit. Once they complete the post-treatment follow-up, participants will then enter the survival follow-up period.

Conditions

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Ovarian Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Alpelisib+olaparib

Alpelisib 200 mg orally once daily and olaparib 200 mg orally twice daily on a continuous dosing schedule.

Group Type EXPERIMENTAL

Alpelisib

Intervention Type DRUG

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

Olaparib

Intervention Type DRUG

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.

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.

Group Type ACTIVE_COMPARATOR

Paclitaxel

Intervention Type DRUG

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

Pegylated liposomal doxorubicin (PLD)

Intervention Type DRUG

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

Interventions

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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

Intervention Type DRUG

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.

Intervention Type DRUG

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

Intervention Type DRUG

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 Type DRUG

Other Intervention Names

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BYL719

Eligibility Criteria

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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

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Arizona Oncology Associates

Phoenix, Arizona, United States

Site Status

HonorHealth

Phoenix, Arizona, United States

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Florida Cancer Specialists

Fort Myers, Florida, United States

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Florida Cancer Specialists

West Palm Beach, Florida, United States

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Maryland Oncology Hematology P A

Silver Spring, Maryland, United States

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Massachusetts General Hospital

Boston, Massachusetts, United States

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Dana Farber Cancer Institute

Boston, Massachusetts, United States

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Memorial Sloan Kettering Cancer Ctr

New York, New York, United States

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Oncology Hematology Care Inc

Cincinnati, Ohio, United States

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University Of Cincinnati

Cincinnati, Ohio, United States

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Avera Cancer Institute

Sioux Falls, South Dakota, United States

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Sarah Cannon Research Institute

Nashville, Tennessee, United States

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Texas Oncology P A

Bedford, Texas, United States

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Texas Oncology

Dallas, Texas, United States

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Texas Oncology P A

San Antonio, Texas, United States

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Texas Oncology Northeast Texas

Tyler, Texas, United States

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Novartis Investigative Site

CABA, Buenos Aires, Argentina

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Ciudad Autonoma de Bs As, Buenos Aires, Argentina

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Buenos Aires, , Argentina

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Bedford Park, South Australia, Australia

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Shepparton, Victoria, Australia

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Sydney, , Australia

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Innsbruck, Tyrol, Austria

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Graz, , Austria

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Brussels, , Belgium

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Leuven, , Belgium

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Namur, , Belgium

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Belo Horizonte, Minas Gerais, Brazil

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São Paulo, São Paulo, Brazil

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Calgary, Alberta, Canada

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Vancouver, British Columbia, Canada

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London, Ontario, Canada

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Toronto, Ontario, Canada

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Chengdu, Sichuan, China

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Beijing, , China

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Jinan, , China

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Shanghai, , China

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Tianjin, , China

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Ostrava, Poruba, Czechia

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Nový Jičín, , Czechia

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Prague, , Czechia

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Herlev, , Denmark

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Odense C, , Denmark

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Kuopio, , Finland

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Tampere, , Finland

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Turku, , Finland

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Besançon, , France

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Lyon, , France

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Paris, , France

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Pierre-Bénite, , France

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Villejuif, , France

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Mannheim, Baden-Wurttemberg, Germany

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Dresden, Saxony, Germany

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Berlin, , Germany

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Essen, , Germany

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Bologna, BO, Italy

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Florence, FI, Italy

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Milan, MI, Italy

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Milan, MI, Italy

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Roma, RM, Italy

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Vicenza, VI, Italy

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Napoli, , Italy

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Kuala Lumpur, Kuala Lumpur, Malaysia

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Kota Kinabalu, Sabah, Malaysia

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Kuching, Sarawak, Malaysia

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Kuala Lumpur, , Malaysia

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Monterrey, Nuevo León, Mexico

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Mexico City, , Mexico

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Eindhoven, , Netherlands

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Loures, , Portugal

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Porto, , Portugal

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Arkhangelsk, , Russia

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Singapore, , Singapore

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Singapore, , Singapore

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Bratislava, , Slovakia

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Seoul, , South Korea

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Seoul, , South Korea

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Barcelona, Catalonia, Spain

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Pamplona, Navarre, Spain

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Barcelona, , Spain

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Córdoba, , Spain

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Madrid, , Spain

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Valencia, , Spain

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Taichung, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Izmir, Karsiyaka, Turkey (Türkiye)

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Ankara, Sihhiye-Altindag, Turkey (Türkiye)

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Adana, Yuregir, Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Glasgow, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

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Countries

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United States Argentina Australia Austria Belgium Brazil Canada China Czechia Denmark Finland France Germany Italy Malaysia Mexico Netherlands Portugal Russia Singapore Slovakia South Korea Spain Taiwan Turkey (Türkiye) United Kingdom

References

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Konstantinopoulos PA, Gonzalez-Martin A, Cruz FM, Friedlander M, Glasspool R, Lorusso D, Marth C, Monk BJ, Kim JW, Hinson P, Ajipa O, Pretre V, Han Y, Matulonis UA. EPIK-O/ENGOT-OV61: alpelisib plus olaparib vs cytotoxic chemotherapy in high-grade serous ovarian cancer (phase III study). Future Oncol. 2022 Oct;18(31):3481-3492. doi: 10.2217/fon-2022-0666. Epub 2022 Sep 6.

Reference Type DERIVED
PMID: 36066851 (View on PubMed)

Other Identifiers

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2019-004682-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CBYL719K12301

Identifier Type: -

Identifier Source: org_study_id

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