A Phase II Randomized, Open Label Non-inferiority Study of NiraParib Maintenance After 3 vs. 6 Cycles of Platinum-based Chemotherapy in completeLy debUlked Advanced HRDpositive High-grade Ovarian Cancer patientS in First Line Therapy

NCT ID: NCT05460000

Last Updated: 2025-04-27

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

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

640 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-10-11

Study Completion Date

2032-10-01

Brief Summary

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Multicenter, randomized, open label study including patients with advanced HRDpositive high-grade ovarian cancer, fallopian tube cancer, primary peritoneal cancer and clear cell carcinoma of the ovary with no residual tumor mass following primary tumor debulking to determine recurrence free survival in patients treated with 3 cycles carboplatin + paclitaxel and maintenance therapy with niraparib vs. 6 cycles carboplatin + paclitaxel and maintenance therapy with niraparib.

Detailed Description

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This is a multicenter, randomized, open label study including patients with advanced (FIGO stage IIIA, IIIB, IIIC, or IV of the 2014 FIGO classification) HRDpositive high-grade ovarian cancer, fallopian tube cancer, primary peritoneal cancer and clear cell carcinoma of the ovary with no residual tumor mass following primary tumor debulking.

The main scope of the trial is to determine recurrence free survival in patients treated with 3 cycles carboplatin + paclitaxel and maintenance therapy with niraparib vs. 6 cycles carboplatin + paclitaxel and maintenance therapy with niraparib.

Patients will be randomized 1:1 to receive either 3 cycles carboplatin + paclitaxel maintenance therapy with niraparib (Arm A) or 6 cycles carboplatin + paclitaxel and maintenance therapy with niraparib (Arm B). Randomization will be performed according to the results of the NGS analysis and stratified either to BRCAm independent of LOH or LOHhigh/ BRCAwt, FIGO stage III vs. IV, and countries. In both of the arms, tumor assessments (CT or MRI) will be performed 9-12 weeks after the start of therapy (after 3rd cycle of chemotherapy), after another 9-12 weeks (during maintenance therapy in Arm A and after the 6th cycle of chemotherapy in Arm B) and every 6 months thereafter. The tumor marker CA-125 will be assessed every 12 weeks in both arms.

During chemotherapy treatment, clinical visits (blood cell counts, detection of toxicity) occur at least every 3 weeks (depending on the chemotherapy regimen). Serum pregnancy tests for WOCBP occur at least every 4 weeks. During maintenance therapy with niraparib, clinical visits (blood cell counts, detection of toxicity) occur every 4 weeks for the first 11 months and every 12 weeks thereafter. Serum pregnancy tests for WOCBP occur at least every 4 weeks. Complete physical examinations will take place every 12 weeks. Safety will be monitored continuously by careful monitoring of all adverse events (AEs) and serious adverse events (SAEs).

About 60 sites in 6 European countries will participate in this study to recruit 640 patients in 36 months.

Conditions

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Ovarian Cancer Fallopian Tube Cancer Primary Peritoneal Carcinoma Clear Cell Carcinoma

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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Arm A (3 cycles of chemotherapy + maintenance therapy with niraparib)

3 cycles carboplatin + paclitaxel maintenance therapy with niraparib (starting dose 200 mg QD or 300 mg QD); maintenance continues until disease progression and/or death, unacceptable adverse event/s, patient and/or investigator decision, other protocol stopping criteria.

Group Type EXPERIMENTAL

3 cycles chemotherapy instead of 6 cycles chemotherapy

Intervention Type DRUG

We hypothesise that recurrence free survival in patients receiving 3 cycles of chemotherapy followed by maintenance with niraparib is not inferior to 6 cycles of chemotherapy followed by niraparib in advanced HRDpositive high-grade ovarian cancer patients with no residual tumor mass following primary tumor debulking.

Arm B (6 cycles of chemotherapy + maintenance therapy with niraparib)

6 cycles carboplatin + paclitaxel and maintenance therapy with niraparib (starting dose 200 mg QD or 300 mg QD); maintenance continues until disease progression and/or death, unacceptable adverse event/s, patient and/or investigator decision, other protocol stopping criteria.

Group Type ACTIVE_COMPARATOR

6 cycles chemotherapy

Intervention Type DRUG

Standard chemotherapy as comparator

Interventions

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3 cycles chemotherapy instead of 6 cycles chemotherapy

We hypothesise that recurrence free survival in patients receiving 3 cycles of chemotherapy followed by maintenance with niraparib is not inferior to 6 cycles of chemotherapy followed by niraparib in advanced HRDpositive high-grade ovarian cancer patients with no residual tumor mass following primary tumor debulking.

Intervention Type DRUG

6 cycles chemotherapy

Standard chemotherapy as comparator

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Written informed consent and obtained from the subject prior to performing any protocol-related procedures, including screening evaluations.
2. Female patient, age ≥ 18 years.
3. FIGO Stage III-IV high-grade ovarian cancer (all histological types, except mucinous histology)
4. Complete primary debulked patients (without any macroscopic residuals), confirmed by CT-Scan postoperatively.
5. Patients must have formalin-fixed, paraffin-embedded tumor samples available from the primary cancer for central NGS analysis and must be HRDpositive defined as BRCAmut independent of NOGGO GIS Score OR NOGGO GIS Score \>83 independent of BRCA status, based on these results.
6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
7. Patients must be able to take oral medications.
8. Synchronous and secondary malignancies are allowed if the prognosis of the ovarian cancer is not affected. The investigator must contact the medical monitoring team before enrolling the patient in the clinical trial.
9. Patients must have normal organ and bone marrow function:

1. Hemoglobin ≥ 10.0 g/dL independent of transfusion ≤ 14 days prior to screening hemoglobin assessment
2. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
3. Platelet count ≥ 100 x 109/L
4. Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN); \< 2 × ULN if hyperbilirubinemia is due to Gilbert's syndrome
5. Aspartate aminotransferase /Serum Glutamic Oxaloacetic Transaminase (ASAT/SGOT)) and Alanine aminotransferase /Serum Glutamic Pyruvate Transaminase (ALAT/SGPT)) ≤ 2,5 x ULN
6. Serum creatinine ≤ 1.5 x institutional ULN and creatinine clearance \> 30 mL/min.
10. Postmenopausal or evidence of non-childbearing status for women of childbearing potential prior to the first dose of study treatment. Female patients of childbearing potential must have a negative serum pregnancy test result ≤3 days prior to administration of the first dose of study treatment.

Patients are considered to be of childbearing potential unless 1 of the following applies:

1. Considered to be permanently sterile. Permanent sterilization includes hysterectomy, bilateral salpingectomy, and/or bilateral oophorectomy; or
2. Is postmenopausal, defined as no menses for at least 12 months without an alternative medical cause. A high follicle-stimulating hormone (FSH) level consistently in the postmenopausal range (30 mIU/mL or higher) may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy; however, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient to confirm a postmenopausal state.

Female patients of reproductive potential must practice highly effective methods (failure rate \< 1% per year) of contraception with their partners, if of reproductive potential, during treatment and for 6 months following the last dose of chemotherapy or the last dose of niraparib, whichever occurs later, or longer if requested by local authorities. Highly effective contraception includes: Ongoing use of progesterone only injectable or implantable contraceptives; Placement of an intrauterine device (IUD) or intrauterine system (IUS); Bilateral tubal occlusion; Sexual abstinence as defined as complete or true abstinence, acceptable only when it is the usual and preferred lifestyle of the patient; periodic abstinence (e.g., calendar, symptothermal, post-ovulation methods) is not acceptable; or Sterilization of the male partner, with appropriate post-vasectomy documentation of absence of sperm in ejaculate.

17. Participation in another clinical study with an investigational product immediately prior to randomization. Earliest time point for randomization is after the time required for the investigational product to undergo 5 half-lives has passed.
18. Has a known history of Human Immunodeficiency Virus (HIV) infection (known HIV1/HIV2 antibodies positive) or acquired immunodeficiency syndrome (AIDS) related illness.
19. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] has been detected) infection.
20. Has active infection with SARS-CoV-2 (antigen test).
21. Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of chemotherapy treatment and while and 28 days after the last dose of trial treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, BCG, and typhoid vaccine. Administration of inactivated vaccines is allowed.
22. Patient has contraindications listed in the most recent SmPC.
23. Patient who might be dependent on the sponsor, CRO, site or the investigator.

22\. In Germany: Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities § 40a S. 1 Nr. 2 AMG.

Exclusion Criteria

1. Non-epithelial origin of the ovary, the fallopian tube or the peritoneum (i.e., germ cell tumors) and Ovarian tumors of low malignant potential (e.g., borderline tumors), or mucinous carcinoma of the ovary.
2. Low-grade ovarian, fallopian tube or peritoneal cancer.
3. Has known hypersensitivity to any of the study drugs or any of the excipients of any of the study drugs.
4. Has known hypersensitivity to platin-containing compounds other than carboplatin.
5. Patients posttransplant, including previous allogeneic bone marrow transplant.
6. Has undergone interval debulking of the tumor.
7. Has received any anti-cancer therapy for ovarian cancer other than primary surgery.
8. Administration of other simultaneous chemotherapy drugs, any other anti-cancer therapy or anti-neoplastic hormonal therapy, or simultaneous radiotherapy during the trial treatment period (hormonal replacement therapy is permitted as are steroidal antiemetics).
9. Has received prior treatment with a PARP inhibitor or has participated in a trial where any treatment arm included the administration of a PARP inhibitor.
10. Bevacizumab is planned to be given together with first line chemotherapy or as maintenance.
11. Clinically significant cardiovascular disease:

1. Cerebrovascular accident or myocardial infarction or unstable angina ≤6 months before start of study treatment
2. Severe cardiac arrhythmia (recent event or active or uncontrolled)
3. New York Heart Association grade ≥2 congestive heart failure
4. Uncontrolled hypertension (defined as systolic blood pressure \>140 mmHg and/or diastolic blood pressure \>90 mmHg), or history of hypertensive crisis, or hypertensive encephalopathy or posterior reversible encephalopathy syndrome
5. History of stroke or transient ischemic attack ≤6 months before start of study treatment
6. Coronary/peripheral artery bypass graft ≤6 months before start of study treatment
7. Deep vein thrombosis or thromboembolic events ≤1 month before start of study treatment
12. History or evidence of brain metastases or spinal cord compression.
13. Known history of MDS or a pre-treatment cytogenetic testing result at risk for a diagnosis of MDS/AML.
14. Current, clinically relevant bowel obstruction at the time of randomization.
15. Patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

OTHER

Sponsor Role collaborator

North Eastern German Society of Gynaecological Oncology

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jalid Sehouli, Prof. Dr. med.

Role: PRINCIPAL_INVESTIGATOR

Lead coordinating investigator (LKP) according to AMG and representative of the sponsor

Locations

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Universitätsklinik Innsbruck

Innsbruck, , Austria

Site Status RECRUITING

Cliniques Universitaires St. Luc

Brussels, , Belgium

Site Status NOT_YET_RECRUITING

Jessa ziekenhuis

Hasselt, , Belgium

Site Status NOT_YET_RECRUITING

UZ Leuven

Leuven, , Belgium

Site Status NOT_YET_RECRUITING

University Hospital Ostrava

Ostrava, , Czechia

Site Status NOT_YET_RECRUITING

General University Hospital in Prague

Prague, , Czechia

Site Status NOT_YET_RECRUITING

University Hospital Bulovka

Prague, , Czechia

Site Status NOT_YET_RECRUITING

Universitätsklinikum Aachen

Aachen, , Germany

Site Status RECRUITING

Klinikum Mittelbaden Baden-Baden Bühl

Baden-Baden, , Germany

Site Status NOT_YET_RECRUITING

DRK-Kliniken Berlin-Köpenick

Berlin, , Germany

Site Status RECRUITING

Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum

Berlin, , Germany

Site Status RECRUITING

ZAHO Bonn Onkologische Praxis

Bonn, , Germany

Site Status RECRUITING

Uniklinikum Bonn

Bonn, , Germany

Site Status NOT_YET_RECRUITING

Klinikum Lippe

Detmold, , Germany

Site Status NOT_YET_RECRUITING

Universitätsklinikum Carl Gustav Carus

Dresden, , Germany

Site Status RECRUITING

Florence-Nightingale-Krankenhaus Düsseldorf-Kaiserswerth

Düsseldorf, , Germany

Site Status NOT_YET_RECRUITING

Universitätsklinikum Freiburg

Freiburg im Breisgau, , Germany

Site Status NOT_YET_RECRUITING

Universitätsklinik Göttingen

Göttingen, , Germany

Site Status NOT_YET_RECRUITING

Universitätsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Site Status NOT_YET_RECRUITING

SLK-Kliniken Heilbronn

Heilbronn, , Germany

Site Status NOT_YET_RECRUITING

Universitätsklinikum Schleswig-Holstein Campus Kiel

Kiel, , Germany

Site Status NOT_YET_RECRUITING

Universitätsklinikum Leipzig

Leipzig, , Germany

Site Status NOT_YET_RECRUITING

Universitätsklinik der Johannes-Gutenberg Universität Mainz

Mainz, , Germany

Site Status RECRUITING

Diakonie Klinikum Schwäbisch Hall

Schwäbisch Hall, , Germany

Site Status NOT_YET_RECRUITING

Christliches Klinikum Unna Mitte

Unna, , Germany

Site Status RECRUITING

Helios Dr. Horst Schmidt Kliniken Wiesbaden

Wiesbaden, , Germany

Site Status RECRUITING

Policlinico St. Orsola Malpighi

Bologna, , Italy

Site Status NOT_YET_RECRUITING

ASST Spedali Civili di Brescia

Brescia, , Italy

Site Status NOT_YET_RECRUITING

ASST Lecco - Ospedale A. Manzoni

Lecco, , Italy

Site Status NOT_YET_RECRUITING

IRCCS Istituto nazionale dei Tumori

Milan, , Italy

Site Status NOT_YET_RECRUITING

AOU Cagliari

Monserrato, , Italy

Site Status NOT_YET_RECRUITING

Istituto Oncologico Veneto (IOV)

Padua, , Italy

Site Status NOT_YET_RECRUITING

Azienda Ospedaliera Universitaria Pisana

Pisa, , Italy

Site Status NOT_YET_RECRUITING

Azienda USL IRCCS Di Reggio Emilia

Reggio Emilia, , Italy

Site Status NOT_YET_RECRUITING

AO Ordine Mauriziano

Torino, , Italy

Site Status NOT_YET_RECRUITING

AOU Città della Salute e della Scienza di Torino - Ospedale Sant'Anna

Torino, , Italy

Site Status NOT_YET_RECRUITING

Hospital General Universitario Dr. Balmis

Alicante, , Spain

Site Status NOT_YET_RECRUITING

Hospital Virgen de las Nieves

Granada, , Spain

Site Status NOT_YET_RECRUITING

Hospital Universitario Lucus Augusti

Lugo, , Spain

Site Status NOT_YET_RECRUITING

CIOCC Clara Campal

Madrid, , Spain

Site Status NOT_YET_RECRUITING

H. Althaia Manresa

Manresa, , Spain

Site Status NOT_YET_RECRUITING

H.U. Virgen de la Macarena

Seville, , Spain

Site Status NOT_YET_RECRUITING

Hospital Universitario Virgen del Rocío

Seville, , Spain

Site Status NOT_YET_RECRUITING

Hospital Universitario Sant Joan de Reus

Tarragona, , Spain

Site Status NOT_YET_RECRUITING

Hospital General Universitario de Valencia

Valencia, , Spain

Site Status NOT_YET_RECRUITING

Hospital La Fe

Valencia, , Spain

Site Status NOT_YET_RECRUITING

Countries

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Austria Belgium Czechia Germany Italy Spain

Central Contacts

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Jessica Nguyen

Role: CONTACT

4930403686539

Jasmin Yamamoto

Role: CONTACT

4930403686532

Facility Contacts

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Annamaria Ferrero, MD

Role: primary

Dionyssios Katsaros

Role: primary

Inmaculada Lozano

Role: primary

Lucía Castillo Portellano

Role: primary

Silvia Varela

Role: primary

Arantzazu Barquin

Role: primary

Silvia Catot

Role: primary

Maria del Mar Gordón

Role: primary

Purificación Estevez

Role: primary

Maria Masvidal Hernánez

Role: primary

Cristina Caballero Díaz

Role: primary

Helena de la Cueva

Role: primary

Christian Marth, Prof. Dr.

Role: primary

Jean-François Baurain, MD

Role: primary

Eric Joosens, MD

Role: primary

Toon Van Gorp, Prof. Dr.

Role: primary

Jan Kümmel, MD

Role: primary

Filip Frühauf, MD

Role: primary

Michal Zikán, Prof. MD

Role: primary

Philipp Meyer-Wilmes, Dr.

Role: primary

Antje Hahn, Dr.

Role: primary

Jessika Goldmann, Dr.

Role: primary

Jalid Sehouli, Prof. Dr.

Role: primary

Martin Esser, Dr.

Role: primary

Alexander Mustea, Prof. Dr.

Role: primary

Beyhan Ataseven, Prof. Dr.

Role: primary

Pauline Wimberger, Prof. Dr.

Role: primary

Saher Baransi, Dr.

Role: primary

Ingolf Juhasz-Böss, Prof. Dr.

Role: primary

Julia K.S. Gallwas, Prof. Dr.

Role: primary

Barbara Schmalfeldt, Prof. Dr.

Role: primary

Amelie de Gregorio, Prof. Dr.

Role: primary

Sandra Brügge, Dr.

Role: primary

Bahriye Aktas, Prof. Dr.

Role: primary

Roxana Schwab, Dr.

Role: primary

Suzana Mittelstadt

Role: primary

Cosmin-Paul Sarac, Dr.

Role: primary

Michael Eichbaum, Prof. Dr.

Role: primary

Claudio Zamagni

Role: primary

Valentina Zizioli, Dr.

Role: primary

Antonio Ardizzoia, Dr.

Role: primary

Francesco Raspagliesi, MD

Role: primary

Elena Massa, MD

Role: primary

Giulia Tasca, MD

Role: primary

Carmelo Bengala, Dr.

Role: primary

Alessandra Bologna

Role: primary

Other Identifiers

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NOGGO-ov53

Identifier Type: -

Identifier Source: org_study_id

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