Clinical trial NCT02655016: A Study of Niraparib (GSK3985771) Maintenance Treatment in Participants With Advanced Ovarian Cancer Following Response on Front-Line Platinum-Based Chemotherapy
Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Niraparib Maintenance Treatment in Patients With Advanced Ovarian Cancer Following Response on Front-Line Platinum-Based Chemotherapy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Ovarian Neoplasms
Keywords: Ovarian Cancer
Niraparib
GSK3985771
Poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP)Inhibitor
Homologous recombination deficiency (HRD)
HRD positive
PRIMA
PRIMA Clinical Trial
PRIMA Study
Lead sponsor: Tesaro, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Gynecologic Oncology Group
name: European Network of Gynaecological Oncological Trial Groups (ENGOT)
name: Myriad Genetics, Inc.
First posted: 2016-01-13
Enrollment: 733
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study aims to assess efficacy of Niraparib (GSK3985771) as maintenance treatment in participants with Stage III or IV ovarian cancer. Participants must have completed front-line platinum based regimen with complete response (CR) or partial response (PR). Data collection for Secondary Outcome measures is ongoing and the approximate duration of the study will be 7 years.


Eligibility criteria: Inclusion criteria:

* Participants must have histologically diagnosed high-grade serous or endometrioid, or high-grade predominantly serous or endometrioid ovarian cancer, fallopian tube cancer, or primary peritoneal cancer that is Stage III or IV according to Federation Internationale de Gynécologie et d'Obstétrique (FIGO) criteria.
* Participants with inoperable Stage III and IV disease; All Stage IV participants with operable disease; Participants with stage III or IV disease treated with neoadjuvant chemotherapy and interval debulking surgery; and Participants with stage III disease who have visible residual disease after primary debulking surgery.
* Participants who have received intraperitoneal chemotherapy; All participants must have had more than or equal to (\>=)6 and less than or equal to (\<=)9 cycles of platinum-based therapy; Participants must have had \>=2 post-operative cycles of platinum-based therapy following interval debulking surgery; Participants must have physician assessed Complete response (CR) or Partial response (PR) after \>=3 cycles of therapy; and Participants must have either Cancer antigen 125 (CA-125) in the normal range or CA-125 decrease by more than 90 percent(%) during their front-line therapy that is stable for at least 7 days (no increase more than (\>)15% from nadir).
* Participants must be randomized within 12 weeks of the first day of the last cycle of chemotherapy.
* All participants must agree to undergo central tumor HRD testing.
* Participants of childbearing potential must have a negative serum or urine pregnancy test (beta human chorionic gonadotropin \[hCG\]) within 7 days prior to receiving the first dose of study treatment.

Exclusion criteria:

* Participant has mucinous or clear cell subtypes of epithelial ovarian cancer, carcinosarcoma or undifferentiated ovarian cancer.
* Participants with Stage III disease who have had complete cytoreduction (no visible residual disease) after primary debulking surgery.
* Participant has undergone more than two debulking surgeries for the study disease.
* Participant is pregnant, breastfeeding, or expecting to conceive children while receiving study treatment and for up to 180 days after the last dose of study treatment.
* Participant has a known hypersensitivity to the components of niraparib or its excipients.
* Participant has received prior treatment with a known PARP inhibitor or has participated in a study where any treatment arm included administration of a known PARP inhibitor.
* Participant is to receive bevacizumab as maintenance treatment.
* Participant has had investigational therapy administered within 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is longer, prior to the first scheduled day of dosing in this study.
* Participant has had any known \>=Grade 3 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted \>4 weeks.
* Participant has a condition (such as transfusion dependent anemia or thrombocytopenia), therapy, or laboratory abnormality that might confound the study results or interfere with the participation for the full duration of the study treatment, including:

  1. Participant received a transfusion (platelets or red blood cells) within 2 weeks of the first dose of study treatment.
  2. Participant received colony-stimulating factors (e.g., granulocyte colony stimulating factor \[G-CSF\], granulocyte macrophage colony-stimulating factor \[GM-CSF\] or recombinant erythropoietin) within 2 weeks prior to the first dose of study treatment.
* Participant has been diagnosed and/or treated for invasive cancer less than 5 years prior to study enrollment.

Primary outcomes:
measure: Progression Free Survival
timeFrame: Up to 34 months
Secondary outcomes:
measure: Overall Survival
timeFrame: Up to 34 months
measure: Time to First Subsequent Therapy (TFST)
timeFrame: Up to 34 months
measure: Progression-Free Survival-2 (PFS2)
timeFrame: Up to 34 months
measure: Change From Baseline in Participant Reported Outcome (PRO): Functional Assessment of Cancer Therapy-Ovarian Symptom Index (FOSI)
timeFrame: Baseline (Day 1, Pre-dose) and Up to Week 24
measure: Change From Baseline in PRO: European Quality of Life Scale, 5-dimensions, 5-levels of Severity (EQ-5D-5L) Utility Score
timeFrame: Baseline (Day 1, Pre-dose) and Up to Week 24
measure: Change From Baseline in Functional Scales of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC-QLQ-C30)
timeFrame: Baseline (Day 1, Pre-dose) and Up to Week 24
measure: Change From Baseline in Global Health Status/QoL of EORTC-QLQ-C30
timeFrame: Baseline (Day 1, Pre-dose) and Up to Week 24
measure: Change From Baseline in Symptoms Scales and Symptoms Items (Dyspnea, Appetite Loss, Insomnia, Constipation, Diarrhea and Financial Difficulty) of EORTC-QLQ-C30
timeFrame: Baseline (Day 1, Pre-dose) and Up to Week 24
measure: Change From Baseline in Functional Scales of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Ovarian Cancer Module (EORTC-QLQ-OV28)
timeFrame: Baseline (Day 1, Pre-dose) and Up to 34 months
measure: Change From Baseline in Symptoms Scale of EORTC-QLQ-OV28
timeFrame: Baseline (Day 1, Pre-dose) and Up to 34 months
Other outcomes:
measure: Number of Participants With Any Non-serious Adverse Event (Non-SAE) or Any SAE
timeFrame: Up to 34 months
measure: Area Under the Curve (AUC) From 0 to the Last Quantifiable Concentration (AUC[0-last])
timeFrame: Up to 34 months
measure: Peak Plasma Concentration (Cmax)
timeFrame: Up to 34 months
measure: Number of Participants With Positive HRD Test
timeFrame: Up to 34 months
Locations:
city: Tempe
country: United States
facility: GSK Investigational Site
state: Arizona
city: Tucson
country: United States
facility: GSK Investigational Site
state: Arizona
city: Tucson
country: United States
facility: GSK Investigational Site
state: Arizona
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: San Francisco
country: United States
facility: GSK Investigational Site
state: California
city: San Francisco
country: United States
facility: GSK Investigational Site
state: California
city: Santa Rosa
country: United States
facility: GSK Investigational Site
state: California
city: Hartford
country: United States
facility: GSK Investigational Site
state: Connecticut
city: New Haven
country: United States
facility: GSK Investigational Site
state: Connecticut
city: Hollywood
country: United States
facility: GSK Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Augusta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Savannah
country: United States
facility: GSK Investigational Site
state: Georgia
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Geneva
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facility: GSK Investigational Site
state: Illinois
city: Hinsdale
country: United States
facility: GSK Investigational Site
state: Illinois
city: Warrenville
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facility: GSK Investigational Site
state: Illinois
city: Indianapolis
country: United States
facility: GSK Investigational Site
state: Indiana
city: Indianapolis
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facility: GSK Investigational Site
state: Indiana
city: Iowa City
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facility: GSK Investigational Site
state: Iowa
city: Baton Rouge
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Covington
country: United States
facility: GSK Investigational Site
state: Louisiana
city: New Orleans
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facility: GSK Investigational Site
state: Louisiana
city: Baltimore
country: United States
facility: GSK Investigational Site
state: Maryland
city: Rockville
country: United States
facility: GSK Investigational Site
state: Maryland
city: Burlington
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Springfield
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Grand Rapids
country: United States
facility: GSK Investigational Site
state: Michigan
city: Minneapolis
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Springfield
country: United States
facility: GSK Investigational Site
state: Missouri
city: Springfield
country: United States
facility: GSK Investigational Site
state: Missouri
city: Middletown
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Neptune
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Teaneck
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Buffalo
country: United States
facility: GSK Investigational Site
state: New York
city: Harrison
country: United States
facility: GSK Investigational Site
state: New York
city: Mineola
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Rochester
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facility: GSK Investigational Site
state: New York
city: Chapel Hill
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Wilmington
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Cleveland
country: United States
facility: GSK Investigational Site
state: Ohio
city: Cleveland
country: United States
facility: GSK Investigational Site
state: Ohio
city: Columbus
country: United States
facility: GSK Investigational Site
state: Ohio
city: Mayfield Hts
country: United States
facility: GSK Investigational Site
state: Ohio
city: Oklahoma City
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facility: GSK Investigational Site
state: Oklahoma
city: Tulsa
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Portland
country: United States
facility: GSK Investigational Site
state: Oregon
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Willow Grove
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Providence
country: United States
facility: GSK Investigational Site
state: Rhode Island
city: Charleston
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Sioux Falls
country: United States
facility: GSK Investigational Site
state: South Dakota
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: The Woodlands
country: United States
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state: Texas
city: Tyler
country: United States
facility: GSK Investigational Site
state: Texas
city: Salt Lake City
country: United States
facility: GSK Investigational Site
state: Utah
city: Kennewick
country: United States
facility: GSK Investigational Site
state: Washington
city: Seattle
country: United States
facility: GSK Investigational Site
state: Washington
city: Spokane
country: United States
facility: GSK Investigational Site
state: Washington
city: Morgantown
country: United States
facility: GSK Investigational Site
state: West Virginia
city: Milwaukee
country: United States
facility: GSK Investigational Site
state: Wisconsin
city: Bonheiden
country: Belgium
facility: GSK Investigational Site
city: Bruxelles
country: Belgium
facility: GSK Investigational Site
city: Bruxelles
country: Belgium
facility: GSK Investigational Site
city: Charleroi
country: Belgium
facility: GSK Investigational Site
city: Gent
country: Belgium
facility: GSK Investigational Site
city: Hasselt
country: Belgium
facility: GSK Investigational Site
city: Leuven
country: Belgium
facility: GSK Investigational Site
city: Libramont
country: Belgium
facility: GSK Investigational Site
city: Namur
country: Belgium
facility: GSK Investigational Site
city: Sint-Niklaas
country: Belgium
facility: GSK Investigational Site
city: Calgary
country: Canada
facility: GSK Investigational Site
state: Alberta
city: Kelowna
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Surrey
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Vancouver
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Barrie
country: Canada
facility: GSK Investigational Site
state: Ontario
city: London
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Ottawa
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
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state: Ontario
city: Toronto
country: Canada
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state: Ontario
city: Montreal
country: Canada
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state: Quebec
city: Montreal
country: Canada
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state: Quebec
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Ostrava
country: Czechia
facility: GSK Investigational Site
city: Plzen
country: Czechia
facility: GSK Investigational Site
city: Prague
country: Czechia
facility: GSK Investigational Site
city: Prague
country: Czechia
facility: GSK Investigational Site
city: Aalborg
country: Denmark
facility: GSK Investigational Site
city: Herlev
country: Denmark
facility: GSK Investigational Site
city: Koebenhavn
country: Denmark
facility: GSK Investigational Site
city: Odense C
country: Denmark
facility: GSK Investigational Site
city: Kuopio
country: Finland
facility: GSK Investigational Site
city: Oulu
country: Finland
facility: GSK Investigational Site
city: Tampere
country: Finland
facility: GSK Investigational Site
city: Turku
country: Finland
facility: GSK Investigational Site
city: Angers cedex 9
country: France
facility: GSK Investigational Site
city: Caen Cedex 5
country: France
facility: GSK Investigational Site
city: Montpellier Cedex 5
country: France
facility: GSK Investigational Site
city: Nice
country: France
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city: Paris
country: France
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city: Paris
country: France
facility: GSK Investigational Site
city: Pierre Benite Cedex
country: France
facility: GSK Investigational Site
city: Rennes Cedex
country: France
facility: GSK Investigational Site
city: Saint-Herblain cedex
country: France
facility: GSK Investigational Site
city: Aachen
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Dresden
country: Germany
facility: GSK Investigational Site
city: Essen
country: Germany
facility: GSK Investigational Site
city: Fuerth
country: Germany
facility: GSK Investigational Site
city: Goettingen
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Heidelberg
country: Germany
facility: GSK Investigational Site
city: Hildesheim
country: Germany
facility: GSK Investigational Site
city: Mannheim
country: Germany
facility: GSK Investigational Site
city: Muenchen
country: Germany
facility: GSK Investigational Site
city: Munchen
country: Germany
facility: GSK Investigational Site
city: Debrecen
country: Hungary
facility: GSK Investigational Site
city: Gyor
country: Hungary
facility: GSK Investigational Site
city: Dublin 8
country: Ireland
facility: GSK Investigational Site
city: Dunmore RoadWaterford
country: Ireland
facility: GSK Investigational Site
city: Galway
country: Ireland
facility: GSK Investigational Site
city: Beer Sheva
country: Israel
facility: GSK Investigational Site
city: Haifa
country: Israel
facility: GSK Investigational Site
city: Haifa
country: Israel
facility: GSK Investigational Site
city: Holon
country: Israel
facility: GSK Investigational Site
city: Petach Tikva
country: Israel
facility: GSK Investigational Site
city: Ramat Gan
country: Israel
facility: GSK Investigational Site
city: Tel Aviv
country: Israel
facility: GSK Investigational Site
city: Candiolo
country: Italy
facility: GSK Investigational Site
city: Lecce
country: Italy
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Mirano VE
country: Italy
facility: GSK Investigational Site
city: Modena
country: Italy
facility: GSK Investigational Site
city: Napoli
country: Italy
facility: GSK Investigational Site
city: Oslo
country: Norway
facility: GSK Investigational Site
city: Lublin
country: Poland
facility: GSK Investigational Site
city: Olsztyn
country: Poland
facility: GSK Investigational Site
city: Poznan
country: Poland
facility: GSK Investigational Site
city: Arkhangelsk
country: Russian Federation
facility: GSK Investigational Site
city: Chelyabinsk
country: Russian Federation
facility: GSK Investigational Site
city: Irkutsk
country: Russian Federation
facility: GSK Investigational Site
city: Ivanovo
country: Russian Federation
facility: GSK Investigational Site
city: Kazan
country: Russian Federation
facility: GSK Investigational Site
city: Krasnoyarsk
country: Russian Federation
facility: GSK Investigational Site
city: Orenburg
country: Russian Federation
facility: GSK Investigational Site
city: Pyatigorsk
country: Russian Federation
facility: GSK Investigational Site
city: Samara
country: Russian Federation
facility: GSK Investigational Site
city: St Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: St Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: St-Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Badalona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Cordoba
country: Spain
facility: GSK Investigational Site
city: Elche Alicante
country: Spain
facility: GSK Investigational Site
city: Gerona
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: San SebastiAn
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Zaragoza
country: Spain
facility: GSK Investigational Site
city: Stockholm
country: Sweden
facility: GSK Investigational Site
city: Uppsala
country: Sweden
facility: GSK Investigational Site
city: Basel
country: Switzerland
facility: GSK Investigational Site
city: Bern
country: Switzerland
facility: GSK Investigational Site
city: Frauenfeld
country: Switzerland
facility: GSK Investigational Site
city: Zuerich
country: Switzerland
facility: GSK Investigational Site
city: Dnipropetrovsk
country: Ukraine
facility: GSK Investigational Site
city: Dnipropetrovsk
country: Ukraine
facility: GSK Investigational Site
city: Ivano-Frankivsk
country: Ukraine
facility: GSK Investigational Site
city: Kharkiv
country: Ukraine
facility: GSK Investigational Site
city: Kherson
country: Ukraine
facility: GSK Investigational Site
city: Krivoy Rog
country: Ukraine
facility: GSK Investigational Site
city: Kyiv
country: Ukraine
facility: GSK Investigational Site
city: Vinnytsia
country: Ukraine
facility: GSK Investigational Site
city: Zaporizhzhia
country: Ukraine
facility: GSK Investigational Site
city: Bath
country: United Kingdom
facility: GSK Investigational Site
city: Blackburn
country: United Kingdom
facility: GSK Investigational Site
city: Edinburgh
country: United Kingdom
facility: GSK Investigational Site
city: Exeter
country: United Kingdom
facility: GSK Investigational Site
city: Glasgow
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: Portsmouth
country: United Kingdom
facility: GSK Investigational Site
city: Sheffield
country: United Kingdom
facility: GSK Investigational Site
city: Staffordshire
country: United Kingdom
facility: GSK Investigational Site
city: Truro
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Monk BJ, Barretina-Ginesta MP, Pothuri B, Vergote I, Graybill W, Mirza MR, McCormick CC, Lorusso D, Moore RG, Freyer G, O'Cearbhaill RE, Heitz F, O'Malley DM, Redondo A, Shahin MS, Vulsteke C, Bradley WH, Haslund CA, Chase DM, Pisano C, Holman LL, Perez MJR, DiSilvestro P, Gaba L, Herzog TJ, Bruchim I, Compton N, Shtessel L, Malinowska IA, Gonzalez-Martin A. Niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer: final overall survival results from the PRIMA/ENGOT-OV26/GOG-3012 trial. Ann Oncol. 2024 Nov;35(11):981-992. doi: 10.1016/j.annonc.2024.08.2241. Epub 2024 Sep 14.
citation: Barretina-Ginesta MP, Monk BJ, Han S, Pothuri B, Auranen A, Chase DM, Lorusso D, Anderson C, Abadie-Lacourtoisie S, Cloven N, Braicu EI, Amit A, Redondo A, Shah R, Kebede N, Hawkes C, Gupta D, Woodward T, O'Malley DM, Gonzalez-Martin A. Quality-adjusted time without symptoms of disease or toxicity and quality-adjusted progression-free survival with niraparib maintenance in first-line ovarian cancer in the PRIMA trial. Ther Adv Med Oncol. 2022 Sep 22;14:17588359221126149. doi: 10.1177/17588359221126149. eCollection 2022.
citation: O'Cearbhaill RE, Perez-Fidalgo JA, Monk BJ, Tusquets I, McCormick C, Fuentes J, Moore RG, Vulsteke C, Shahin MS, Forget F, Bradley WH, Hietanen S, O'Malley DM, Dorum A, Slomovitz BM, Baumann K, Selle F, Calvert PM, Artioli G, Levy T, Kumar A, Malinowska IA, Li Y, Gupta D, Gonzalez-Martin A. Efficacy of niraparib by time of surgery and postoperative residual disease status: A post hoc analysis of patients in the PRIMA/ENGOT-OV26/GOG-3012 study. Gynecol Oncol. 2022 Jul;166(1):36-43. doi: 10.1016/j.ygyno.2022.04.012. Epub 2022 May 9.
citation: Gonzalez-Martin A, Pothuri B, Vergote I, DePont Christensen R, Graybill W, Mirza MR, McCormick C, Lorusso D, Hoskins P, Freyer G, Baumann K, Jardon K, Redondo A, Moore RG, Vulsteke C, O'Cearbhaill RE, Lund B, Backes F, Barretina-Ginesta P, Haggerty AF, Rubio-Perez MJ, Shahin MS, Mangili G, Bradley WH, Bruchim I, Sun K, Malinowska IA, Li Y, Gupta D, Monk BJ; PRIMA/ENGOT-OV26/GOG-3012 Investigators. Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med. 2019 Dec 19;381(25):2391-2402. doi: 10.1056/NEJMoa1910962. Epub 2019 Sep 28.