Clinical trial NCT05183984: Niraparib with BeVAcizumab After Complete CytoreductioN in Patients with OvArian Cancer
Official title: Randomized Study of Paclitaxel-carboplatin Followed by Niraparib Compared to Paclitaxel-carboplatin-bevacizumab Followed by Niraparib+bevacizumab in Patients with Advanced Ovarian Cancer, Following a Front-line Complete Surgery
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Ovarian Cancer
Keywords: ovarian cancer
frontline surgery
brca status
maintenance
Lead sponsor: ARCAGY/ GINECO GROUP
Sponsor class: OTHER
First posted: 2022-01-11
Enrollment: 390
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Progression-Free survival (PFS) rate up to 24 months
timeFrame: 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 outcomes:
measure: PFS2
timeFrame: 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.
measure: Number of Participants with abnormal physical examinations, abnormal vital signs and abnormal findings according to CTC-AE v5
timeFrame: Through treatment completion for all participants, an average of 28 months
measure: Time to First Subsequent Treatment
timeFrame: 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.
measure: Time to Second Subsequent Treatment
timeFrame: 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.
measure: Long-term Overall Survival in both arms
timeFrame: from time of signature of informed consent, throughout the study period, assessed up to 5 years
measure: Confirmation of the predictive value (overall chemo-sensitivity) of the KELIM.
timeFrame: From study start until the end of the study, assessed up to 5 years
Other outcomes:
Locations:
city: Angers
country: France
facility: ICO Paul Papin
city: Avignon
country: France
facility: Sainte Catherine Institut du cancer Avignon-Provence
city: Besançon
country: France
facility: CHRU Besançon - Hôpital Jean Minjoz
city: Bordeaux
country: France
facility: Clinique Tivoli-Ducos
city: Bordeaux
country: France
facility: Institut Bergonié
city: Brest
country: France
facility: Hôpital Morvan CHRU de Brest
city: Bron
country: France
facility: HCL - Groupe Hospitalier Est
city: Caen
country: France
facility: Centre François Baclesse
city: Cholet
country: France
facility: Centre Hospitalier de Cholet
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Dijon
country: France
facility: CHU de Dijon - Bourgogne
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: Grenoble
country: France
facility: Groupe Hospitalier Mutualiste de Grenoble - Institut Daniel Hollard
city: La Tronche
country: France
facility: CHU Grenoble-Alpes - Site Nord (La Tronche)
city: Le Mans
country: France
facility: Clinique Victor Hugo
city: Lille
country: France
facility: Centre Oscar Lambret
city: Limoges
country: France
facility: CHU de Limoges - Hôpital Dupuytren
city: Lyon
country: France
facility: Centre Léon Bérard
city: Lyon
country: France
facility: Hôpital Privé Jean Mermoz
city: Lyon
country: France
facility: HCL - Hôpital de la Croix Rousse
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Marseille
country: France
facility: Hôpital Nord Marseille
city: Montpellier
country: France
facility: Institut régional du cancer de Montpellier
city: Montpellier
country: France
facility: CHU Montpellier - Hôpital Saint Eloi
city: Mougins
country: France
facility: Centre Azuréen de Cancérologie
city: Nancy
country: France
facility: ORACLE - Centre d'Oncologie de Gentilly
city: Nantes
country: France
facility: Hôpital Privé du Confluent
city: Nîmes
country: France
facility: Centre ONCOGARD - Institut de cancérologie du Gard
city: Orléans
country: France
facility: CHR Orléans
city: Paris
country: France
facility: Groupe Hospitalier Pitié Salpêtrière
city: Paris
country: France
facility: Hôpital cochin
city: Paris
country: France
facility: Hôpital Saint-Joseph
city: Paris
country: France
facility: Institut Mutualiste Montsouris
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Paris
country: France
facility: Groupe Hospitalier Diaconesses - Croix Saint-Simon
city: Paris
country: France
facility: Hôpital Tenon
city: Pierre-Bénite
country: France
facility: HCL - Centre Hospitalier Lyon Sud (Hospices Civils de Lyon)
city: Plérin
country: France
facility: Centre CARIO - HPCA
city: Poitiers
country: France
facility: CHU de Poitiers - Hôpital de la Milétrie
city: Reims
country: France
facility: Institut Jean Godinot
city: Rennes
country: France
facility: Centre Eugène Marquis
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint-Herblain
country: France
facility: ICO - Centre René Gauducheau
city: Saint-Priest-en-Jarez
country: France
facility: CHU de Saint-Etienne - Pôle de Cancérologie
city: Strasbourg
country: France
facility: ICANS - Institut de cancérologie Strasbourg Europe
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Tours
country: France
facility: CHU Tours - Hôpital Bretonneau
city: Valence
country: France
facility: CH Valence
city: Villejuif
country: France
facility: Gustave Roussy
city: Firenze
country: Italy
facility: Firenze-Careggi
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia (IEO)
city: Monza
country: Italy
facility: Ospedale San Gerardo Monza
city: Sondrio
country: Italy
facility: Presidio Ospedaliero di Sondrio
city: Tokyo
country: Japan
facility: Cancer Institute Hospital Of JFCR
state: Ariake, Koto
city: Kashiwanoha
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Kurume
country: Japan
facility: Kurume University Hospital Clinical Research Center
state: Fukuoka
city: Tsukuba
country: Japan
facility: University of Tsukuba Hospital
state: Ibaraki-Pref
city: Niigata
country: Japan
facility: Niigata Cancer Center Hospital
state: Niigata-ken
city: Kita-ku
country: Japan
facility: Okayama University Hospital
state: Okayama
city: Shimotsuke
country: Japan
facility: Jichi Medical UH
state: Tochigi-ken
city: Ehime
country: Japan
facility: Ehime University Hospital
state: Toonshi
city: Saitama
country: Japan
facility: Saitama Medical University International Medical Center
city: Yamagata
country: Japan
facility: Yamagata University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Gangnam-gu
city: Seoul
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: National University Hospital
state: Jongno-gu
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
state: Seodaemun-gu
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
state: Songpa-gu
city: Singapore
country: Singapore
facility: National University Hospital (NUH)
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
city: A Coruña
country: Spain
facility: Coruña University Hospital (CHUAC)
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Universitari Dexeus
city: Cáceres
country: Spain
facility: Hospital San Pedro de Alcantara
city: El Palmar, Murcia
country: Spain
facility: Hospital Clínico Universitario Virgen de la Arrixaca
city: Jerez de la Frontera
country: Spain
facility: Hospital Universitario de Jerez
city: Madrid
country: Spain
facility: Clínica Universidad de Navarra
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro
city: Málaga
country: Spain
facility: Hospital Virgen de la Victoria
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra.
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra
city: Santiago de Compostela
country: Spain
facility: CHU de Santiago de Compostela
city: Terrassa
country: Spain
facility: Hospital Universitari MutuaTerrassa
city: Valencia
country: Spain
facility: Fundación Investigación Clínico de Valencia.
Study officials:
affiliation: HCL - Centre Hospitalier Lyon Sud
name: Gilles FREYER, Pr
role: PRINCIPAL_INVESTIGATOR
References: