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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05183984
Other study ID # GINECO-OV129b
Secondary ID
Status Recruiting
Phase Phase 2
First received
Last updated
Start date February 1, 2022
Est. completion date February 2030

Study information

Verified date January 2024
Source ARCAGY/ GINECO GROUP
Contact Sidonie Adam
Phone 1 84 85 20 18
Email sadam@arcagy.org
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Randomized, open label, phase II multicenter study to assess the efficacy niraparib versus niraparib +bevacizumab maintenance in patients with newly diagnosed stage IIIA/B/C high-grade epithelial ovarian cancer with no residual disease after frontline surgery and treatment by adjuvant platinum-basedchemotherapy +/-bevacizumab.


Description:

Phase II, randomized, open label, multicenterstudy. Randomization on a 1:1 ratio, stratification performed according to: BRCA status (local assessment) FIGO stage at diagnosis (IIIA versus IIIB/IIIC) Previous hyperthermic intraperitoneal chemotherapy (yes/no).


Recruitment information / eligibility

Status Recruiting
Enrollment 390
Est. completion date February 2030
Est. primary completion date February 2027
Accepts healthy volunteers No
Gender Female
Age group 18 Years to 99 Years
Eligibility Inclusion Criteria: For inclusion in the study, patient should fulfill the following criteria: 1. Female patient = 18 years of age. 2. Signed informed consent and ability to comply with treatment and follow-up. 3. Patient with newly diagnosed, a. Ovarian cancer, primary peritoneal cancer and/or fallopian-tube cancer, b. Histologically confirmed (based on local histopathological findings): • high grade serous or - high grade endometrioid (grade 2 and 3) or - other epithelial non mucinous and non-clear cell ovarian cancer in a patient with germline BRCA 1 or 2 deleterious mutation, c. At an advanced stage: FIGO stage IIIA to IIIC of the 2018 FIGO classification. 4. Patient having undergone frontline, complete cytoreductive surgery (i.e. no visible residual disease): The patient will be considered eligible once the ESGO Quality Assurance in Ovarian Cancer Surgery will have been filled out and validated 5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. 6. Patient must have received one cycle of carboplatin AUC 5-6 + paclitaxel 175 mg/m² 7. Patient must have started cycle 1 chemotherapy no later than 6 weeks after surgery. 8. Patient must have a thorax-abdomen-pelvis CT scan between surgery and Cycle 1, with no evidence of disease. 9. Patient eligible for first line platinum-taxane chemotherapy: 10. Patient eligible for bevacizumab treatment in combination with chemotherapy and in maintenance. It must be started at the second chemotherapy cycle and be administered at a dose of 15mg/kg every 3 weeks up to a total of 15 months. 11. Patient must have normal organ and bone marrow function before first cycle of chemotherapy: - Hemoglobin = 9.0 g/dL. - Absolute neutrophil count (ANC) = 1.5 x 109/L. - Platelet count = 100 x 109/L. - Total bilirubin = 1.5 x institutional upper limit of normal (ULN). - Aspartate aminotransferase/Serum Glutamic Oxaloacetic Transaminase (ASAT/SGOT)) and Alanine aminotransferase /Serum Glutamic Pyruvate Transaminase (ALAT/SGPT)) = 2.5 x ULN. - Serum creatinine = 1. 5 x institutional ULN and GFR > 50 mL/min, by using an exact measure (ie. Iohexol clearance) or the most appropriate formula (Jeliffe, Cockroft Gault, MDRD, CKD-EPI) to the investigator's discretion. - Patient not receiving anticoagulant medication who has an International Normalized Ratio (INR) =1.5 and an Activated ProThrombin Time (aPTT) =1.5 x ULN. The use of full-dose oral or parenteral anticoagulants is permitted as long as the INR or APTT is within therapeutic limits (according to site medical standard). If the patient is on oral anticoagulants, dose has to be stable for at least two weeks at the time of randomization. 12. Urine dipstick for proteinuria < 2+. If urine dipstick is =2+, 24-hour proteinuria must be <1 g. 13. Normal blood pressure or adequately treated and controlled hypertension (systolic BP = 140 mmHg and/or diastolic BP = 90 mmHg). 14. Formalin fixed paraffin embedded (FFPE) tumor sample from the primary cancer must be available for local BRCA testing and if possible HRD testing (optional). 15. For countries where this will apply to: a subject will be eligible for randomization in this study only if either affiliated to, or a beneficiary of a social security category. Exclusion Criteria: - 1. Patient with clear cell adenocarcinoma or carcinosarcoma, non-epithelial origin of the ovarian tumor, the fallopian tube or the peritoneal tumor (i.e. germ cell tumors). 2. Ovarian tumor of low malignant potential (e.g. borderline tumor), or mucinous carcinoma. 3. Patient with a diagnosis, detection, or treatment of another type of cancer = 3 years prior to initiating protocol therapy (except basal or squamous cell carcinoma of the skin and cervical cancer in situ that has been definitively treated and synchronous grade 1 stage 1 endometrial cancer) Patient with history of primary triple negative breast cancer may be eligible provided she completed her definitive anticancer treatment more than 3 years ago and she remains breast cancer disease free prior to start of study treatment. 4. Patient with synchronous high grade serous or clear cell adenocarcinoma or carcinosarcoma of the endometrium is not eligible. 5. Patient with myelodysplastic syndrome/acute myeloid leukemia history. 6. Patient receiving radiotherapy within 6 weeks prior to study treatment. 7. Previous allogenic bone marrow transplant. 8. Any previous treatment with PARP inhibitor. 9. Administration of other simultaneous chemotherapy drugs - except during a HIPEC procedure with cisplatin at PDS, any other anticancer therapy or anti-neoplastic hormonal therapy, or simultaneous radiotherapy during the trial treatment period (hormonal replacement therapy is permitted as are steroid antiemetics). 10. Current or recent (within 10 days prior to randomization) chronic use of aspirin > 325 mg/day. 11. Prior history of hypertensive crisis (CTC-AE grade 4) or hypertensive encephalopathy. 12. Clinically significant (e.g. active) cardiovascular disease, including: - Myocardial infarction or unstable angina within = 6 months of randomization, - New York Heart Association (NYHA) = grade 2 congestive heart failure (CHF), - Poorly controlled cardiac arrhythmia despite medication (patient with rate controlled atrial fibrillation are eligible), or any clinically significant abnormal finding on resting ECG. - Peripheral vascular disease grade = 3 (e.g. symptomatic and interfering with activities of daily living [ADL] requiring repair or revision). 13. Previous Cerebro-Vascular Accident (CVA), Transient Ischemic Attack (TIA), Sub- Arachnoids Hemorrhage (SAH) or Posterior Reversible Encephalopathy Syndrome (PRES). 14. History or evidence of hemorrhagic disorders. 15. Evidence of bleeding diathesis or significant coagulopathy (in the absence of coagulation). 16. History or clinical suspicion of brain metastases or spinal cord compression. CT/MRI of the brain is mandatory (within 4 weeks prior to randomization) in case of suspected brain metastases. Spinal MRI is mandatory (within 4 weeks prior to randomization) in case of suspected spinal cord compression. 17. History or evidence upon neurological examination of central nervous system (CNS) disease, unless adequately treated with standard medical therapy (e.g. uncontrolled seizures). 18. Significant traumatic injury during 4 weeks prior to randomization. 19. Non-healing wound, active ulcer, or bone fracture. Patient with granulating incisions healing by secondary intention with no evidence of facial dehiscence or infection is eligible but require 3 weekly wound examinations. 20. History of VEGF therapy related abdominal fistula or gastrointestinal perforation or active gastrointestinal bleeding within 6 months prior to the first study treatment. 21. Current, clinically relevant bowel obstruction, including sub-occlusive disease, related to underlying disease. 22. Patient with evidence of abdominal free air not explained by paracentesis or recent surgical procedure. 23. Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment related complications. 24. Pregnant or lactating women. 25. Participation in another clinical study with any intravenous or oral investigational product is not allowed. However, participation in a surgical clinical study including Hyperthermic Chemotherapy (HIPEC) during the surgical procedure is allowed. 26. Patient unable to swallow orally administered medication and patient with gastrointestinal disorders likely to interfere with absorption of the study medication. 27. Patient with a known contraindication or uncontrolled hypersensitivity to the components of paclitaxel, carboplatin, niraparib, bevacizumab, or their excipients. 28. Immunocompromised patient, e.g., with known active hepatitis (i.e. Hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids or patient who is known to be serologically positive for human immunodeficiency virus (HIV). 29. Participant has a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent.

Study Design


Intervention

Drug:
Chemotherapy
Chemotherapy (carboplatin + paclitaxel) will be administred by intravenous infusion, AUC 5-6 q3w - 5 cycles during the treatment period
Bevacizumab-Awwb
MVASI (bevacizumab biosimilar) will be administrated by intravenous infusion at the second chemotherapy cycle for 5 cycles. the administration will continue during maintenance phase. Total bevacizumab duration therapy is 15 months.
Niraparib
niraparib will be administered orally once daily continuously after chemotherapy (+/- bevacizumab) cycles (maintenance treatment period). Total niraparib duration mainance treatment period is 2 years.

Locations

Country Name City State
France ICO Paul Papin Angers
France Sainte Catherine Institut du cancer Avignon-Provence Avignon
France CHRU Besançon - Hôpital Jean Minjoz Besançon
France Clinique Tivoli-Ducos Bordeaux
France Institut Bergonié Bordeaux
France Hôpital Morvan CHRU de Brest Brest
France HCL - Groupe Hospitalier Est Bron
France Centre François Baclesse Caen
France Centre Hospitalier de Cholet Cholet
France Centre Jean Perrin Clermont-Ferrand
France Centre Georges François Leclerc Dijon
France CHU de Dijon - Bourgogne Dijon
France Groupe Hospitalier Mutualiste de Grenoble - Institut Daniel Hollard Grenoble
France CHU Grenoble-Alpes - Site Nord (La Tronche) La Tronche
France Centre Oscar Lambret Lille
France CHU de Limoges - Hôpital Dupuytren Limoges
France Centre Léon Bérard Lyon
France HCL - Hôpital de la Croix Rousse Lyon
France Hôpital Privé Jean Mermoz Lyon
France Hôpital Nord Marseille Marseille
France Institut Paoli Calmettes Marseille
France Institut régional du cancer de Montpellier Montpellier
France Centre Azuréen de Cancérologie Mougins
France ORACLE - Centre d'Oncologie de Gentilly Nancy
France Hôpital Privé du Confluent Nantes
France Centre ONCOGARD - Institut de cancérologie du Gard Nîmes
France CHR Orléans Orléans
France Groupe Hospitalier Diaconesses - Croix Saint-Simon Paris
France Groupe Hospitalier Pitié Salpêtrière Paris
France Hôpital cochin Paris
France Hôpital Européen Georges Pompidou Paris
France Hôpital Tenon Paris
France Institut Mutualiste Montsouris Paris
France HCL - Centre Hospitalier Lyon Sud (Hospices Civils de Lyon) Pierre-Bénite
France Centre CARIO - HPCA Plérin
France CHU de Poitiers - Hôpital de la Milétrie Poitiers
France Institut Jean Godinot Reims
France Centre Eugène Marquis Rennes
France Centre Henri Becquerel Rouen
France ICO - Centre René Gauducheau Saint-Herblain
France CHU de Saint-Etienne - Pôle de Cancérologie Saint-Priest-en-Jarez
France ICANS - Institut de cancérologie Strasbourg Europe Strasbourg
France Institut Claudius Regaud Toulouse
France CHU Tours - Hôpital Bretonneau Tours
France Gustave Roussy Villejuif
Japan Saitama Medical University International Medical Center Saitama

Sponsors (1)

Lead Sponsor Collaborator
ARCAGY/ GINECO GROUP

Countries where clinical trial is conducted

France,  Japan, 

Outcome

Type Measure Description Time frame Safety issue
Primary Progression-Free survival (PFS) rate up to 24 months Progression-Free Survival (PFS) is defined as time from randomization until objective tumor progression or death, whichever occurs first, assessed up to 24 months.
Secondary PFS2 PFS2 is defined as time from randomization to objective tumor progression on next-line treatment or death from any cause, assessed up to 5 years.
Secondary Number of Participants with abnormal physical examinations, abnormal vital signs and abnormal findings according to CTC-AE v5 Through treatment completion for all participants, an average of 28 months
Secondary Time to First Subsequent Treatment TFST is defined as the time from the date of randomization to date of the first subsequent anticancer therapy or death, assessed up to 5 years.
Secondary Time to Second Subsequent Treatment TSST is defined as the time from the date of randomization to the earlier of the date of second subsequent chemotherapy start date, or death date, assessed up to 5 years.
Secondary Long-term Overall Survival in both arms from time of signature of informed consent, throughout the study period, assessed up to 5 years
Secondary Confirmation of the predictive value (overall chemo-sensitivity) of the KELIM. Repeated CA-125 assay repeated through study completion From study start until the end of the study, assessed up to 5 years
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