A Maintenance Study With Niraparib Versus Placebo in Patients With Platinum Sensitive Ovarian Cancer

NCT01847274 | Completed Phase 3 Results DMC

• 2 other identifiers: 213356PR-30-5011-C
• Study Type: interventional
• Target: 596
• Locations: 15 countries
• Sites: 112

Brief Summary

This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study of niraparib as maintenance in platinum sensitive ovarian cancer patients who have either gBRCAmut or a tumor with high-grade serous histology and who have responded to their most recent chemotherapy containing a platinum agent. Niraparib is an orally active PARP inhibitor. Niraparib or placebo (in a 2:1 ratio) will be administered once daily continuously during a 28-day cycle. Health-related quality of life will be measured by the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI), European Quality of Life scale, 5-Dimensions (EQ-5D), and a neuropathy questionnaire. Safety and tolerability will be assessed by clinical review of adverse events (AEs), physical examinations, electrocardiograms (ECGs), and safety laboratory values. The primary objective of this study is to evaluate efficacy of niraparib as maintenance therapy in patients who have platinum sensitive ovarian cancer as assessed by the prolongation of progression free survival (PFS).

Conditions

Ovarian Neoplasms; Platinum Sensitive Ovarian Cancer

Keywords

ovarian cancer; platinum sensitive; gBRCAmut; BRCA; high-grade serous histology; PARP inhibitor

Outcome Measures

Primary Outcomes (3)

• Progression-Free Survival (PFS) in Cohort With Germline BReast CAncer Gene (BRCA) Mutation (gBRCA)

  PFS was defined as the time between randomization and disease progression or death from any cause. Computed tomography or magnetic resonance imaging to assess disease progression was performed at baseline, every 8 weeks through cycle 14, and then every 12 weeks until treatment discontinuation. The objective assessment of disease progression was determined by means of central radiologic and clinical review, according to Response Evaluation Criteria in Solid Tumors (RECIST),version 1.1, which was performed in a blinded fashion. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.

  From date of randomization to the earliest date of disease progression or death from any cause, up to 7 years 7 months and 4 days

• Progression-Free Survival (PFS) in Cohort With No Germline BCRA With Homologous Recombination Deficiency-positive (HRD+) Tumors (Non-gBRCAmut HRD+)

  PFS was defined as the time between randomization and disease progression or death from any cause. Computed tomography or magnetic resonance imaging to assess disease progression was performed at baseline, every 8 weeks through cycle 14, and then every 12 weeks until treatment discontinuation. The objective assessment of disease progression was determined by means of central radiologic and clinical review, according to Response Evaluation Criteria in Solid Tumors (RECIST),version 1.1, which was performed in a blinded fashion. PD was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.

  From date of randomization to the earliest date of disease progression or death from any cause, up to 7 years, 7 months and 4 days

• Progression-Free Survival (PFS) in Cohort With No Germline BRCA Mutation

  PFS was defined as the time between randomization and disease progression or death from any cause. Computed tomography or magnetic resonance imaging to assess disease progression was performed at baseline, every 8 weeks through cycle 14, and then every 12 weeks until treatment discontinuation. The objective assessment of disease progression was determined by means of central radiologic and clinical review, according to Response Evaluation Criteria in Solid Tumors (RECIST),version 1.1, which was performed in a blinded fashion.PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.

  From date of randomization to the earliest date of disease progression or death from any cause, up to 7 years, 7 months and 4 days

Secondary Outcomes (48)

• Time to First Subsequent Therapy in Cohort With Germline BRCA Mutation (gBRCA)

  From date of randomization to the earliest date of first subsequent therapy or death, up to 7 years, 7 months and 4 days

• Time to First Subsequent Therapy in Cohort With No Germline BRCA Mutation

  From date of randomization to the earliest date of first subsequent therapy or death, up to 7 years, 7 months and 4 days

• Chemotherapy-Free Interval in Cohort With Germline BRCA Mutation (gBRCA)

  From date of last platinum therapy prior to randomization to the initiation of the next anti-cancer therapy after maintenance treatment, up to 7 years, 7 months and 4 days

• Chemotherapy-Free Interval in Cohort With No Germline BRCA Mutation

  From date of last platinum therapy prior to randomization to the initiation of the next anti-cancer therapy after maintenance treatment, up to 7 years, 7 months and 4 days

• Progression-Free Survival 2 in Cohort With Germline BRCA Mutation (gBRCA)

  From treatment randomization to the earlier of the date of disease progression on the next anti-cancer therapy following study treatment or death due to any cause, up to 7 years, 7 months and 4 days

Study Arms (2)

Niraparib

ACTIVE COMPARATOR

2:1 Ratio administered once daily continuously during a 28 day cycle.

Drug: Active comparator: Niraparib

Placebo

PLACEBO COMPARATOR

Administered once daily continuously over a 28 day cycle.

Drug: placebo

Interventions

Active comparator: Niraparib DRUG

Niraparib vs placebo 2:1 ratio

Also known as: Niraparib

Niraparib

placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age or older, female, any race
• Histologically diagnosed ovarian cancer, fallopian tube cancer or primary peritoneal cancer
• High grade (or grade 3) serous histology or known to have gBRCAmut
• Has received at least 2 previous courses of platinum-containing therapy, and has disease that was considered platinum sensitive following the penultimate (next to last) platinum course (more than 6 month period between penultimate platinum regimen and progression of disease)
• Has responded to last the platinum regimen, remains in response and is enrolled on study within 8 weeks of completion of the last platinum regimen
• ECOG 0-1
• Adequate bone marrow, kidney and liver function

You may not qualify if:

• Known hypersensitivity to the components of niraparib
• Invasive cancer other than ovarian cancer within 2 years (except basal or squamous cell carcinoma of the skin that has been definitely treated)
• Symptomatic uncontrolled brain metastasis
• Is pregnant or breast feeding
• Immunocompromised patients
• Known active hepatic disease
• Prior treatment with a known PARP inhibitor

Sponsors & Collaborators

• Tesaro, Inc.: lead
• European Network of Gynaecological Oncological Trial Groups (ENGOT): collaborator
• Myriad Genetics, Inc.: collaborator
• US Oncology Research: collaborator
• Sarah Cannon: collaborator
• Cooperative Ovarian Cancer Group (COGI): collaborator
• Facing Our Risk of Cancer Empowered: collaborator

Study Sites (112)

GSK Investigational Site

Phoenix, Arizona, 85013, United States

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GSK Investigational Site

Tucson, Arizona, 85704, United States

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GSK Investigational Site

Los Angeles, California, 90027, United States

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GSK Investigational Site

Los Angeles, California, 90048, United States

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GSK Investigational Site

Palo Alto, California, 94304, United States

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GSK Investigational Site

San Francisco, California, 94109, United States

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GSK Investigational Site

New Haven, Connecticut, 06510, United States

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Sarasota, Florida, 34232, United States

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Tampa, Florida, 33612, United States

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Atlanta, Georgia, 30342, United States

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Chicago, Illinois, 60611, United States

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GSK Investigational Site

Indianapolis, Indiana, 46202, United States

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GSK Investigational Site

Indianapolis, Indiana, 46260, United States

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GSK Investigational Site

Boston, Massachusetts, 02115, United States

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GSK Investigational Site

Boston, Massachusetts, 02215, United States

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GSK Investigational Site

Burlington, Massachusetts, 01805, United States

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Minneapolis, Minnesota, 55404, United States

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Minneapolis, Minnesota, 55455, United States

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Rochester, Minnesota, 55905, United States

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Morristown, New Jersey, 07962-1956, United States

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Farmington, New Mexico, 87401, United States

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GSK Investigational Site

Lake Success, New York, 11042, United States

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GSK Investigational Site

New York, New York, 10016, United States

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GSK Investigational Site

New York, New York, 10065, United States

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Durham, North Carolina, 27710, United States

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Oklahoma City, Oklahoma, 73104, United States

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GSK Investigational Site

Vancouver, Oregon, 98684, United States

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Abington, Pennsylvania, 19001-3788, United States

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Philadelphia, Pennsylvania, 19111, United States

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Providence, Rhode Island, 02905, United States

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Nashville, Tennessee, 37203, United States

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Austin, Texas, 78731, United States

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Dallas, Texas, 75390, United States

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Fort Worth, Texas, 76104, United States

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The Woodlands, Texas, 77380, United States

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Graz, A-8036, Austria

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Innsbruck, A-6020, Austria

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Vienna, 1090, Austria

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Edegem, 2650, Belgium

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Kortrijk, 8500, Belgium

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Leuven, 3000, Belgium

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Liège, 4000, Belgium

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Calgary, Alberta, T2N 4N2, Canada

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Kelowna, British Columbia, V1Y 5L3, Canada

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Vancouver, British Columbia, V5Z 4E6, Canada

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Toronto, Ontario, M5G 2M9, Canada

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Montreal, Quebec, H2L 4M1, Canada

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Montreal, Quebec, H3T 1E2, Canada

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Montreal, Quebec, H4A 3J1, Canada

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Sherbrooke, Quebec, J1H 5N4, Canada

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Aalborg, 9100, Denmark

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Copenhagen, DK-2100, Denmark

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Herlev, DK-2730, Denmark

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Odense, 5000, Denmark

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Besançon, 25030, France

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Lille, 59000, France

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Montpellier, 34298, France

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Nice, 06189, France

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Saint-Brieuc, 22015 cedex, France

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Saint-Herblain, 44805, France

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Heidelberg, Baden-Wurttemberg, 69120, Germany

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Munich, Bavaria, 81377, Germany

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Göttingen, Lower Saxony, 37075, Germany

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Hanover, Lower Saxony, 30177, Germany

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Düsseldorf, North Rhine-Westphalia, 40217, Germany

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Essen, North Rhine-Westphalia, 45122, Germany

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Essen, North Rhine-Westphalia, 45136, Germany

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Dresden, Saxony, 01307, Germany

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Kiel, Schleswig-Holstein, 24105, Germany

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Berlin, 13353, Germany

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Hamburg, 20246, Germany

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Szolnok, 5004, Hungary

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Haifa, 3109601, Israel

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Holon, 58100, Israel

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Jerusalem, 91031, Israel

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Jerusalem, 91120, Israel

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Kfar Saba, 44281, Israel

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Rehovot, 76100, Israel

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Tel Aviv, 64239, Israel

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Tel Litwinsky, 52621, Israel

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Rome, Lazio, 00168, Italy

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Brescia, Lombardy, 25123, Italy

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Milan, Lombardy, 20141, Italy

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Catania, Sicily, 95126, Italy

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Milan, 20133, Italy

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Bergen, 5021, Norway

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Oslo, 0379, Norway

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Bialystok, 15-207, Poland

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Gdansk, 80-219, Poland

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Lodz, 94-029, Poland

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Poznan, 60-569, Poland

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GSK Investigational Site

Oviedo, Principality of Asturias, 33011, Spain

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Barcelona, 08907, Spain

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GSK Investigational Site

Barcelona, 8035, Spain

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GSK Investigational Site

Madrid, 28033, Spain

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GSK Investigational Site

Madrid, 28040, Spain

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GSK Investigational Site

Madrid, 28046, Spain

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GSK Investigational Site

Palma de Mallorca, 07198, Spain

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GSK Investigational Site

Linköping, SE-581 85, Sweden

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GSK Investigational Site

Lund, SE-221 85, Sweden

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Stockholm, SE-171 76, Sweden

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Nottingham, Nottinghamshire, NG5 1PB, United Kingdom

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Yeovil, Somerset, BA21 4AT, United Kingdom

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Birmingham, West Midlands, B18 7QH, United Kingdom

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Bebington, Wirral, CH63 4JY, United Kingdom

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London, NW1 2PG, United Kingdom

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GSK Investigational Site

London, SE1 9RT, United Kingdom

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GSK Investigational Site

London, SW3 6JJ, United Kingdom

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London, SW36JJ, United Kingdom

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GSK Investigational Site

Maidstone, ME16 9QQ, United Kingdom

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GSK Investigational Site

Rhyl, LL18 5UJ, United Kingdom

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GSK Investigational Site

Taunton, TA1 5DA, United Kingdom

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Related Publications (9)

• Mirza MR, Monk BJ, Herrstedt J, Oza AM, Mahner S, Redondo A, Fabbro M, Ledermann JA, Lorusso D, Vergote I, Ben-Baruch NE, Marth C, Madry R, Christensen RD, Berek JS, Dorum A, Tinker AV, du Bois A, Gonzalez-Martin A, Follana P, Benigno B, Rosenberg P, Gilbert L, Rimel BJ, Buscema J, Balser JP, Agarwal S, Matulonis UA; ENGOT-OV16/NOVA Investigators. Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer. N Engl J Med. 2016 Dec 1;375(22):2154-2164. doi: 10.1056/NEJMoa1611310. Epub 2016 Oct 7.

  PMID: 27717299 BACKGROUND

• Mirza MR, Lindahl G, Mahner S, Redondo A, Fabbro M, Rimel BJ, Herrstedt J, Oza AM, Canzler U, Berek JS, Gonzalez-Martin A, Follana P, Lord R, Azodi M, Estenson K, Wang Z, Li Y, Gupta D, Matulonis U, Feng B. Ad hoc Analysis of the Phase III ENGOT-OV16/NOVA Study: Niraparib Efficacy in Germline BRCA Wild-type Recurrent Ovarian Cancer with Homologous Recombination Repair Defects. Cancer Res Commun. 2022 Nov 15;2(11):1436-1444. doi: 10.1158/2767-9764.CRC-22-0240. eCollection 2022 Nov.

  PMID: 36970052 BACKGROUND

• Monk BJ, Romero I, Graybill W, Churruca C, O'Malley DM, Knudsen AO, Yap OWS, Baurain JF, Rose PG, Denys H, Ghamande S, Pisano C, Fabbro M, Braicu EI, Calvert PM, Amit A, Prendergast E, Taylor A, Kheibarshekan L, Zhang ZY, Zajic S, Jewell RC, Gupta D, Gonzalez-Martin A. Niraparib Population Pharmacokinetics and Exposure-Response Relationships in Patients With Newly Diagnosed Advanced Ovarian Cancer. Clin Ther. 2024 Aug;46(8):612-621. doi: 10.1016/j.clinthera.2024.06.001. Epub 2024 Jul 16.

  PMID: 39019698 DERIVED

• Tattersall A, Ryan N, Wiggans AJ, Rogozinska E, Morrison J. Poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of ovarian cancer. Cochrane Database Syst Rev. 2022 Feb 16;2(2):CD007929. doi: 10.1002/14651858.CD007929.pub4.

  PMID: 35170751 DERIVED

• Mirza MR, Benigno B, Dorum A, Mahner S, Bessette P, Barcelo IB, Berton-Rigaud D, Ledermann JA, Rimel BJ, Herrstedt J, Lau S, du Bois A, Herraez AC, Kalbacher E, Buscema J, Lorusso D, Vergote I, Levy T, Wang P, de Jong FA, Gupta D, Matulonis UA. Long-term safety in patients with recurrent ovarian cancer treated with niraparib versus placebo: Results from the phase III ENGOT-OV16/NOVA trial. Gynecol Oncol. 2020 Nov;159(2):442-448. doi: 10.1016/j.ygyno.2020.09.006. Epub 2020 Sep 25.

  PMID: 32981695 DERIVED

• Matulonis UA, Walder L, Nottrup TJ, Bessette P, Mahner S, Gil-Martin M, Kalbacher E, Ledermann JA, Wenham RM, Woie K, Lau S, Marme F, Casado Herraez A, Hardy-Bessard AC, Banerjee S, Lindahl G, Benigno B, Buscema J, Travers K, Guy H, Mirza MR. Niraparib Maintenance Treatment Improves Time Without Symptoms or Toxicity (TWiST) Versus Routine Surveillance in Recurrent Ovarian Cancer: A TWiST Analysis of the ENGOT-OV16/NOVA Trial. J Clin Oncol. 2019 Dec 1;37(34):3183-3191. doi: 10.1200/JCO.19.00917. Epub 2019 Sep 16.

  PMID: 31518175 DERIVED

• Del Campo JM, Matulonis UA, Malander S, Provencher D, Mahner S, Follana P, Waters J, Berek JS, Woie K, Oza AM, Canzler U, Gil-Martin M, Lesoin A, Monk BJ, Lund B, Gilbert L, Wenham RM, Benigno B, Arora S, Hazard SJ, Mirza MR. Niraparib Maintenance Therapy in Patients With Recurrent Ovarian Cancer After a Partial Response to the Last Platinum-Based Chemotherapy in the ENGOT-OV16/NOVA Trial. J Clin Oncol. 2019 Nov 10;37(32):2968-2973. doi: 10.1200/JCO.18.02238. Epub 2019 Jun 7.

  PMID: 31173551 DERIVED

• Oza AM, Matulonis UA, Malander S, Hudgens S, Sehouli J, Del Campo JM, Berton-Rigaud D, Banerjee S, Scambia G, Berek JS, Lund B, Tinker AV, Hilpert F, Vazquez IP, D'Hondt V, Benigno B, Provencher D, Buscema J, Agarwal S, Mirza MR. Quality of life in patients with recurrent ovarian cancer treated with niraparib versus placebo (ENGOT-OV16/NOVA): results from a double-blind, phase 3, randomised controlled trial. Lancet Oncol. 2018 Aug;19(8):1117-1125. doi: 10.1016/S1470-2045(18)30333-4. Epub 2018 Jul 17.

  PMID: 30026000 DERIVED

• Berek JS, Matulonis UA, Peen U, Ghatage P, Mahner S, Redondo A, Lesoin A, Colombo N, Vergote I, Rosengarten O, Ledermann J, Pineda M, Ellard S, Sehouli J, Gonzalez-Martin A, Berton-Rigaud D, Madry R, Reinthaller A, Hazard S, Guo W, Mirza MR. Safety and dose modification for patients receiving niraparib. Ann Oncol. 2018 Aug 1;29(8):1784-1792. doi: 10.1093/annonc/mdy181.

  PMID: 29767688 DERIVED

Related Links

• Facing our risk of cancer empowered website

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

niraparib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Results Point of Contact

• Title: GSK Response Center
• Organization: GSK

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Studies

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2013
• First Posted: May 6, 2013
• Study Start: June 21, 2013
• Primary Completion: April 22, 2016
• Study Completion: December 26, 2021
• Last Updated: June 2, 2023
• Results First Posted: May 1, 2019

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

SE (3); GB (11); PL (4); BE (4); AU (3); DE (11); FR (6); NO (2); US (35); HU (1); DK (4); IL (8); CA (8); IT (5); ES (7)