Clinical trial • Phase II • Oncology

NIRAPARIB TOSILATE MONOHYDRATE for High-grade ovarian cancer (HRD-positive, stage III-IV) | Fallopian tube cancer | Primary peritoneal cancer | Ovarian clear cell carcinoma

Phase II trial of NIRAPARIB TOSILATE MONOHYDRATE for High-grade ovarian cancer (HRD-positive, stage III-IV) | Fallopian tube cancer | Primary peritoneal c…

Overview

Trial Therapeutic Area
Oncology
Trial Disease
High-grade ovarian cancer (HRD-positive, stage III-IV) | Fallopian tube cancer | Primary peritoneal cancer | Ovarian clear cell carcinoma
Trial Stage
Phase II
Drug Modality
Small molecule
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
31-07-2023
First CTIS Authorization Date
01-03-2024

Trial design

Randomised, open-label, two randomized arms: 3 cycles of platinum-based chemotherapy followed by niraparib maintenance versus 6 cycles of platinum-based chemotherapy followed by niraparib maintenance. platinum-based chemotherapy agents listed in the protocol include carboplatin (dose information in dossier: max daily dose 400 mg/m2) and paclitaxel (max daily dose 175 mg/m2). niraparib maintenance oral formulation listed with max daily dose 300 mg.-controlled Phase II trial in Germany, Austria, Czechia and others.

Randomised
Yes
Open Label
Yes
Comparator
Two randomized arms: 3 cycles of platinum-based chemotherapy followed by niraparib maintenance versus 6 cycles of platinum-based chemotherapy followed by niraparib maintenance. Platinum-based chemotherapy agents listed in the protocol include carboplatin (dose information in dossier: max daily dose 400 mg/m2) and paclitaxel (max daily dose 175 mg/m2). Niraparib maintenance oral formulation listed with max daily dose 300 mg.
Target Sample Size
640

Eligibility

Recruits 640 Only adult female participants (age ≥ 18) are eligible. Written informed consent must be obtained from the subject prior to any protocol procedures. No vulnerable populations selected in the application metadata. There is a country-specific exclusion in Germany for patients who have been incarcerated or involuntarily institutionalised. No assent procedures or under-18 consent described (minors excluded)..

Pregnancy Exclusion
Pregnant or lactating women, women of child-bearing potential who do not agree to the usage of highly effective contraception methods (see inclusion criteria) starting with the screening visit through at least 6 months after the last dose of chemotherapy treatment or through at least 1 month after the last dose of niraparib, whichever occurs later.
Vulnerable Population
Only adult female participants (age ≥ 18) are eligible. Written informed consent must be obtained from the subject prior to any protocol procedures. No vulnerable populations selected in the application metadata. There is a country-specific exclusion in Germany for patients who have been incarcerated or involuntarily institutionalised. No assent procedures or under-18 consent described (minors excluded).

Inclusion criteria

  • {"criterion_text":"- Written informed consent and obtained from the subject prior to performing any protocol-related procedures, including screening evaluations.\n- 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: a. Considered to be permanently sterile. Permanent sterilization includes hysterectomy, bilateral salpingectomy, and/or bilateral oophorectomy; or b. 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.\n- Female patient, age ≥ 18 years.\n- FIGO Stage III-IV high-grade ovarian cancer (all histological types, except mucinous histology)\n- Complete primary debulked patients (without any macroscopic residuals), confirmed by CT-Scan postoperatively.\n- Patients must have formalin-fixed, paraffin-embedded tumor samples available from the primary cancer for central NGS analysis and must be HRD positive defined as BRCAmut independent of NOGGO GIS Score OR NOGGO GIS Score >83 independent of BRCA status, based on these results\n- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.\n- Patients must be able to take oral medications.\n- 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.\n- Patients must have normal organ and bone marrow function: a. Hemoglobin ≥ 10.0 g/dL independent of transfusion ≤ 14 days prior to screening hemoglobin assessment b. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L c. Platelet count ≥ 100 x 109/L d. Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN); < 2 × ULN if hyperbilirubinemia is due to Gilbert’s syndrome e. Aspartate aminotransferase /Serum Glutamic Oxaloacetic Transaminase (ASAT/SGOT)) and Alanine aminotransferase /Serum Glutamic Pyruvate Transaminase (ALAT/SGPT)) ≤ 2,5 x ULN f. Serum creatinine ≤ 1.5 x institutional ULN and creatinine clearance > 30 mL/min."}

Exclusion criteria

  • {"criterion_text":"- 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.\n- Bevacizumab is planned to be given together with first line chemotherapy or as maintenance.\n- Clinically significant cardiovascular disease: a.\tCerebrovascular accident or myocardial infarction or unstable angina ≤6 months before start of study treatment b.\tSevere cardiac arrhythmia (recent event or active or uncontrolled) c.\tNew York Heart Association grade ≥2 congestive heart failure d.\tUncontrolled 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 e.\tHistory of stroke or transient ischemic attack ≤6 months before start of study treatment f.\tCoronary/peripheral artery bypass graft ≤6 months before start of study treatment g.\tDeep vein thrombosis or thromboembolic events ≤1 month before start of study treatment\n- History or evidence of brain metastases or spinal cord compression.\n- Known history of MDS or a pre-treatment cytogenetic testing result at risk for a diagnosis of MDS/AML.\n- Current, clinically relevant bowel obstruction at the time of randomization.\n- Patients with gastrointestinal disorders likely to interfere with absorption of the study medication.\n- Pregnant or lactating women, women of child-bearing potential who do not agree to the usage of highly effective contraception methods (see inclusion criteria) starting with the screening visit through at least 6 months after the last dose of chemotherapy treatment or through at least 1 month after the last dose of niraparib, whichever occurs later.\n- 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.\n- Has a known history of Human Immunodeficiency Virus (HIV) infection (known HIV1/HIV2 antibodies positive) or acquired immunodeficiency syndrome (AIDS) related illness.\n- 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.\n- Low-grade ovarian, fallopian tube or peritoneal cancer.\n- Has active infection with SARS-CoV-2 (antigen test).\n- Patient who might be dependent on the sponsor, CRO, site or the investigator.\n- In Germany: Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities § 40a S. 1 Nr. 2 AMG.\n- Has known hypersensitivity to any of the study drugs or any of the excipients of any of the study drugs.\n- Has known hypersensitivity to platin-containing compounds other than carboplatin.\n- Patients posttransplant, including previous allogeneic bone marrow transplant.\n- Has undergone interval debulking of the tumor.\n- Has received any anti-cancer therapy for ovarian cancer other than primary surgery.\n- 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).\n- 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."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- RFS (Recurrence free survival, defined as time from treatment randomization to the earliest date of assessment of first relapse or death by any cause)","definition_or_measurement_approach":"Recurrence free survival (RFS) defined as time from treatment randomization to the earliest date of assessment of first relapse or death by any cause."}

Secondary endpoints

  • {"endpoint_text":"- Overall survival (OS) (time to event and rate at 3 and 5 years)","definition_or_measurement_approach":"Time from randomization to death from any cause; rates reported at 3 and 5 years."}
  • {"endpoint_text":"- Time to first subsequent treatment (TFST)","definition_or_measurement_approach":"Time from randomization to the start of first subsequent treatment (e.g., chemotherapy)."}
  • {"endpoint_text":"- TWIST (Time Without Symptoms of disease progression or Toxicity of treatment) at baseline, 3, 6, and 12 months","definition_or_measurement_approach":"Assessment of time without symptoms of disease progression or toxicity of treatment measured at baseline and at 3, 6, and 12 months."}
  • {"endpoint_text":"- PFS2 (Time from randomization until the date of second objective disease progression or death by any cause)","definition_or_measurement_approach":"Time from randomization to second objective progression or death from any cause."}
  • {"endpoint_text":"- PROs (EORTC QLQ-C30 and EORTC QLQ-OV28)","definition_or_measurement_approach":"Patient-reported outcomes measured using EORTC QLQ-C30 and EORTC QLQ-OV28 instruments."}
  • {"endpoint_text":"- Safety assessment includes AEs/SAEs, laboratory evaluations, vital signs and physical examination","definition_or_measurement_approach":"Safety assessed by adverse events/serious adverse events, lab tests, vital signs and physical examinations."}
  • {"endpoint_text":"- Cost effectiveness","definition_or_measurement_approach":"Health economic evaluation / cost-effectiveness analysis (no further detail provided)."}

Recruitment

Planned Sample Size
640
Recruitment Window Months
99
Consent Approach
Written informed consent must be obtained from each participant prior to any protocol procedures; participants are adults (≥18) and provide consent themselves. Subject information and informed consent materials are provided in multiple languages (documents listed in repository include English, German, Spanish, French, Dutch, Italian, Czech). No assent for minors (minors excluded).

Geography

Total Number Of Sites
52
Total Number Of Participants
640

Germany

Earliest CTIS Part Ii Submission Date
21-02-2024
Latest Decision Or Authorization Date
11-02-2026
Processing Time Days
721
Number Of Sites
23
Number Of Participants
300

Sites

Site Name
University Medical Center Hamburg-Eppendorf
Department Name
Klinik für Gynäkologie und Geburtshilfe
Contact Person Name
Barbara Schmalfeldt
Contact Person Email
b.schmalfeldt@uke.de
Site Name
Universitaetsklinikum Koeln AöR
Department Name
Klinik und Poliklinik für Frauenheilkunde und Gynäkologische Onkologie
Contact Person Name
Florin-Andrei Taran
Site Name
Diakonie-Klinikum Schwaebisch Hall gGmbH
Department Name
Gynäkologie
Contact Person Name
Suzana Mittelstadt
Contact Person Email
suzana.mittelstadt@diakoneo.de
Site Name
Universitaet Leipzig
Department Name
Gynäkologie & Geburtshilfe
Contact Person Name
Bahriye Aktas
Site Name
Klinikum Dortmund gGmbH
Department Name
Klinik für Gynäkologie und Geburtshilfe
Contact Person Name
Barbara Kipp
Contact Person Email
Barbara.kipp@klinikumdo.de
Site Name
SLK-Kliniken Heilbronn GmbH
Department Name
Klinik für Frauenheilkunde und Geburtshilfe
Contact Person Name
Amelie De Gregorio
Site Name
Christliches Klinikum Unna gGmbH
Department Name
Klinik für Gynäkologie und Geburtshilfe
Contact Person Name
Cosmin-Paul Sarac
Contact Person Email
b.grigat@hospitalverbund.de
Site Name
Universitaetsmedizin Goettingen
Department Name
Klinik für Gynäkologie und Geburtshilfe
Contact Person Name
Julia Katharina Sophia Gallwas
Site Name
Schwesternschaft Der Krankenfuersorge Des Dritten Ordens KdöR
Department Name
Klinik für Gynäkologie und Geburtshilfe
Contact Person Name
Attila Teoman
Contact Person Email
attila.teoman@gmail.com
Site Name
Universitaetsklinikum Bonn AöR
Department Name
Gynäkologie & Geburtshilfe
Contact Person Name
Alexander Mustea
Contact Person Email
studienzentrale-szb@ukbonn.de
Site Name
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR
Department Name
Klinik für Gynäkologie und Geburtshilfe
Contact Person Name
Roxana Schwab
Site Name
Universitaetsklinikum Aachen AöR
Department Name
Klinik für Gynäkologie und Geburtsmedizin
Contact Person Name
Philipp Meyer-Wilmes
Site Name
HELIOS Dr. Horst Schmidt Kliniken Wiesbaden GmbH
Department Name
Klinik für Frauenheilkunde und Geburtshilfe
Contact Person Name
Michael Eichbaum
Site Name
Kaiserswerther Diakonie
Department Name
Gynäkologie & Gynökoonkologie
Contact Person Name
Saher Baransi
Site Name
Technische Universitat Dresden
Department Name
Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe
Contact Person Name
Pauline Wimberger
Site Name
Zentrum für ambulante Hämatologie und Onkologie
Department Name
Hämatologie und internistische Onkologie
Contact Person Name
Martin Esser
Contact Person Email
studienbuero@zaho-rheinland.de
Site Name
Klinikum Lippe GmbH
Department Name
Gynäkologie & Geburtshilfe
Contact Person Name
Beyhan Ataseven
Site Name
Universitaetsklinikum Schleswig-Holstein AöR
Department Name
Klinik für Gynäkologie und Geburtshilfe
Contact Person Name
Sandra Brügge
Contact Person Email
sandra.bruegge@uksh.de
Site Name
Medical Center - University Of Freiburg
Department Name
Gynäkologie & Geburtshilfe
Contact Person Name
Ingolf Juhasz-Böss
Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Klinik für Gynäkologie mit Zentrum für onkologische Chirurgie (CVK) und Klinik für Gynäkologie (CBF)
Contact Person Name
Jalid Sehouli
Contact Person Email
gyn-Studien@charite.de
Site Name
DRK Kliniken Berlin
Department Name
Klinik für Gynäkologie und Geburtshilfe
Contact Person Name
Jessika Goldmann
Site Name
Universitaetsklinikum Jena KöR
Department Name
Klinik und Poliklinik für Frauenheilkunde und Fortpflanzungsmedizin
Contact Person Name
Dirk Bauerschlag
Site Name
Klinikum Mittelbaden Balg
Department Name
Gynäkologie
Contact Person Name
Antje Hahn

Austria

Earliest CTIS Part Ii Submission Date
12-03-2024
Latest Decision Or Authorization Date
25-03-2024
Processing Time Days
706
Number Of Sites
1
Number Of Participants
20

Sites

Site Name
Medizinische Universitaet Innsbruck
Department Name
University Hospital for Gynaecology and Obstetrics
Contact Person Name
Christian Marth

Czechia

Earliest CTIS Part Ii Submission Date
11-07-2023
Latest Decision Or Authorization Date
12-02-2026
Processing Time Days
937
Number Of Sites
3
Number Of Participants
30

Sites

Site Name
Fakultni Nemocnice Bulovka
Department Name
Gynekologicko-porodnická klinika
Contact Person Name
Michal Zikán
Contact Person Email
michal.zikan@bulovka.cz
Site Name
Fakultni Nemocnice Ostrava
Department Name
Gynekologicko-porodnická klinika
Contact Person Name
Jan Kümmel
Contact Person Email
jan.kummel@fno.cz
Site Name
Vseobecna Fakultni Nemocnice V Praze
Department Name
Klinika gynekologie, porodnictví a neonatologie 1.LF UK a VFN
Contact Person Name
Filip Frühauf
Contact Person Email
filip.fruhauf@vfn.cz

Spain

Earliest CTIS Part Ii Submission Date
12-11-2024
Latest Decision Or Authorization Date
13-02-2026
Processing Time Days
458
Number Of Sites
11
Number Of Participants
120

Sites

Site Name
Hospital Universitario Y Politecnico La Fe
Department Name
Medical Oncology
Contact Person Name
Ana Santaballa
Contact Person Email
santaballa_ana@gva.es
Site Name
Hospital Universitario Lucus Augusti
Department Name
Medical Oncology
Contact Person Name
Silvia Varela Ferreiro
Site Name
Hospital Universitario Virgen De Las Nieves
Department Name
Medical Oncology
Contact Person Name
Lucía Castillo
Contact Person Email
luportellano@gmail.com
Site Name
Hospital Universitario Virgen De La Macarena
Department Name
Medical Oncology
Contact Person Name
M Mar Gordón
Contact Person Email
gordonsantiago@gmail.com
Site Name
University Hospital Virgen Del Rocio S.L.
Department Name
Medical Oncology
Contact Person Name
Purificación Estevez
Contact Person Email
puriestevez@gmail.com
Site Name
Salut Sant Joan De Reus
Department Name
Medical Oncology
Contact Person Name
María Masvidal
Site Name
Althaia Xarxa Assistencial Universitaria De Manresa Fundacio Privada
Department Name
Medical Oncology
Contact Person Name
Silvia Catot
Contact Person Email
scatot@althaia.cat
Site Name
Hospital General Universitario Dr. Balmis
Department Name
Medical Oncology
Contact Person Name
Inmaculada Lozano
Contact Person Email
inmalozanocubo@gmail.com
Site Name
Hospital General Universitario De Valencia
Department Name
Oncology
Contact Person Name
Cristina Caballero
Contact Person Email
caballero_cri@gva.es
Site Name
Clara Campal Comprehensive Cancer Center
Department Name
Medical Oncology
Contact Person Name
Arantzazu Barquin
Contact Person Email
abarquin@hmhospitales.com
Site Name
Hospital Universitario Lucus Augusti (additional entry presumed)
Department Name
Medical Oncology
Contact Person Name
Silvia Varela Ferreiro

Belgium

Earliest CTIS Part Ii Submission Date
02-12-2024
Latest Decision Or Authorization Date
11-02-2026
Processing Time Days
436
Number Of Sites
4
Number Of Participants
50

Sites

Site Name
Universitair Ziekenhuis Gent
Department Name
Medical oncology
Contact Person Name
Hannelore Denys
Contact Person Email
hannelore.denys@ugent.be
Site Name
UZ Leuven
Department Name
Gynecology and obstetrics
Contact Person Name
Toon Van Gorp
Contact Person Email
toon.vangorp@uzleuven.be
Site Name
Jessa Ziekenhuis
Department Name
Medical Oncology
Contact Person Name
Eric Joosens
Contact Person Email
eric.joosens@jessazh.be
Site Name
Cliniques Universitaires Saint-Luc
Department Name
Medical Oncology
Contact Person Name
Jean-Francois Baurain

Italy

Earliest CTIS Part Ii Submission Date
09-12-2024
Latest Decision Or Authorization Date
13-02-2026
Processing Time Days
431
Number Of Sites
10
Number Of Participants
120

Sites

Site Name
Azienda USL IRCCS Di Reggio Emilia
Department Name
Oncologia Medica Provinciale
Contact Person Name
Alessandra Bologna
Contact Person Email
alessandra.bologna@ausl.re.it
Site Name
Azienda Ospedaliera Ordine Mauriziano Di Torino
Department Name
Academic Department Gynaecology and Obstetrics
Contact Person Name
Annamaria Ferrero
Contact Person Email
sperimentazioni@mauriziano.it
Site Name
Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
Department Name
Medical Oncology and Haematology
Contact Person Name
Claudio Zamagni
Contact Person Email
claudio.zamagni@aosp.bo.it
Site Name
Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
Department Name
Gynecology
Contact Person Name
Dionyssios Katsaros
Site Name
Fondazione IRCCS Istituto Nazionale Dei Tumori
Department Name
S.C. Gynecology Oncology
Contact Person Name
Francesco Raspagliesi
Site Name
Azienda Ospedaliero Universitaria Pisana
Department Name
UO Oncologia Medica 1 Universitaria
Contact Person Name
Carmelo Bengala
Site Name
Istituto Oncologico Veneto
Department Name
U.O.C. Oncology 2
Contact Person Name
Giulia Tasca
Contact Person Email
giulia.tasca@iov.veneto.it
Site Name
Azienda Ospedaliero-Universitaria Di Cagliari
Department Name
SC Oncologia Medica
Contact Person Name
Elena Massa
Contact Person Email
elena.massa@unica.it
Site Name
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
Department Name
Obstetrics and Gynecology
Contact Person Name
Valentina Zizioli
Site Name
Alessandro Manzoni Hospital
Department Name
Oncology
Contact Person Name
Antonio Ardizzoia
Contact Person Email
a.ardizzoia@asst-lecco.it

Sponsor

Primary sponsor

Full Name
Nord Ostdeutsche Gesellschaft Fuer Gynaekologische Onkologie e.V.
Organisation Type
Laboratory/Research/Testing facility
Country Of Registered Address
Germany

Third parties

  • {"country":"","full_name":"GlaxoSmithKline Research & Development Limited","duties_or_roles":"Source of monetary support","organisation_type":""}

Investigational products

Investigational Product Name
NIRAPARIB TOSILATE MONOHYDRATE
Active Substance
NIRAPARIB TOSILATE MONOHYDRATE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
prodAuthStatus: 1
Orphan Designation
Yes
Maximum Dose
300 mg
Investigational Product Name
CARBOPLATIN
Active Substance
CARBOPLATIN
Modality
Small molecule
Routes Of Administration
INTRAVENOUS
Route
INTRAVENOUS
Authorisation Status
prodAuthStatus: 2
Maximum Dose
400 mg/m2
Investigational Product Name
PACLITAXEL
Active Substance
PACLITAXEL
Modality
Small molecule
Routes Of Administration
INTRAVENOUS
Route
INTRAVENOUS
Authorisation Status
prodAuthStatus: 2
Maximum Dose
175 mg/m2
Combination Treatment
Yes

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