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Trial record 1 of 1 for:    2021-001271-16
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Niraparib vs Niraparib Plus Bevacizumab in Patients With Platinum/Taxane-based Chemotherapy in Advanced Ovarian Cancer

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ClinicalTrials.gov Identifier: NCT05009082
Recruitment Status : Recruiting
First Posted : August 17, 2021
Last Update Posted : October 28, 2022
Sponsor:
Collaborator:
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Information provided by (Responsible Party):
AGO Study Group

Brief Summary:
This is an international, multicenter, randomized, open, Phase III trial to evaluate the efficacy and safety of carboplatin/paclitaxel/bevacizumab followed by bevacizumab and niraparib compared to carboplatin/paclitaxel followed by niraparib in patients with newly diagnosed advanced ovarian cancer.

Condition or disease Intervention/treatment Phase
Ovarian Cancer Fallopian Tube Cancer Peritoneal Cancer Drug: Carboplatin Drug: Paclitaxel Drug: Bevacizumab Drug: Niraparib Phase 3

Detailed Description:

Eligible patients will be those patients with newly diagnosed, histologically confirmed, advanced (FIGO stage III/IV, except FIGO stage IIIA2 without nodal involvement) invasive high grade epithelial ovarian cancer, peritoneal cancer, or fallopian tube cancer, who have either undergone upfront primary surgery or plan to undergo chemotherapy with interval debulking surgery (IDS). In addition, patients should not have any medical contraindications that would exclude treatment with bevacizumab and/or niraparib.

All eligible patients will receive the first cycle of chemotherapy (carboplatin area under curve [AUC] 5 and paclitaxel 175 mg/m²) as part of Study Run-In-Period (cycle 1). In parallel, central laboratory will determine the breast cancer (BRCA) status in tumor tissue (tBRCA). All patients with a valid central tBRCA test result will be randomized prior to day 1 of cycle 2 in a 1:1 ratio in the following treatment arms:

Arm 1: Patients will receive further 5 cycles of carboplatin and paclitaxel q21d followed by niraparib once daily for up to a total of 3 years

Arm 2: Patients will receive further 5 cycles of carboplatin and paclitaxel plus bevacizumab q21d followed by bevacizumab q21d (for up to 1 year) and niraparib once daily for up to a total of 3 years.

The study aims to investigate, if the treatment strategy of carboplatin / paclitaxel / bevacizumab / niraparib is superior to the treatment of carboplatin / paclitaxel / niraparib-Inhibitor in an all-comer population.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 970 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Niraparib vs Niraparib in Combination With Bevacizumab in Patients With Carboplatinum-taxane Based Chemotherapy in Advanced Ovarian Cancer (A Multicentre Randomised Phase III Trial)
Actual Study Start Date : September 13, 2022
Estimated Primary Completion Date : February 2028
Estimated Study Completion Date : September 2030


Arm Intervention/treatment
Active Comparator: Arm 1
Chemotherapy followed by maintenance with niraparib
Drug: Carboplatin
Area under curve (AUC) 5, intravenous, on day 1 every 3 weeks for 6 cycles

Drug: Paclitaxel
175 mg/m², intravenous, on day 1 every 3 weeks for 6 cycles

Drug: Niraparib
200 or 300 mg capsules once daily for up to a total of 3 years

Active Comparator: Arm 2
Chemotherapy in combination with bevacizumab followed by maintenance with bevacizumab and niraparib
Drug: Carboplatin
Area under curve (AUC) 5, intravenous, on day 1 every 3 weeks for 6 cycles

Drug: Paclitaxel
175 mg/m², intravenous, on day 1 every 3 weeks for 6 cycles

Drug: Bevacizumab
7.5 mg/kg or 15 mg/kg (according to local standard), intravenous, on day 1 every 3 weeks starting from cycle 2 in combination with chemotherapy and thereafter for up to 1 year

Drug: Niraparib
200 or 300 mg capsules once daily for up to a total of 3 years




Primary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: Assessed frequently during the trial until observation of 586 PFS events or three years after Last Patient In, whichever occurs earlier ]
    Defined as the time from randomization to first progressive disease (PD) or death, whichever occurs earlier. PD is based on investigators assessment using the Response Evaluation Criteria in Solid Tumors (RECIST v1.1).


Secondary Outcome Measures :
  1. PFS according to tumor BRCA status [ Time Frame: Assessed frequently during the trial until observation of 586 PFS events or three years after Last Patient In, whichever occurs earlier ]
    Defined as the time from randomization to first progressive disease (PD) or death, whichever occurs earlier. PD is based on investigators assessment using the Response Evaluation Criteria in Solid Tumors (RECIST v1.1).

  2. Overall Survival (OS) [ Time Frame: at every visit during the trial up to 66 months after Last Patient In ]
    Defined as the time from randomization to death

  3. Time to First Subsequent Therapy (TFST) [ Time Frame: at every visit during the trial up to 66 months after Last Patient In ]
    Defined as the time from randomization to the first subsequent treatment or death, whichever occurs earlier

  4. Second Progression (PFS 2) [ Time Frame: at every visit during the trial up to 66 months after Last Patient In ]
    Defined as the time from randomization to the second progression or death, whichever occurs earlier

  5. Time to Second Subsequent Therapy (TSST) [ Time Frame: at every visit during the trial up to 66 months after Last Patient In ]
    Defined as the time from randomization to the second subsequent treatment death whichever occurs earlier

  6. Number of participants with treatment-related adverse events (AE) and/or serious adverse events (SAEs) and/or AEs that led to premature withdrawal of trial treatment and/or interruptions/dose modifications [ Time Frame: at every visit during the trial up to safety follow up visit 30 days after last dose ]
    Graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

  7. Effects on Quality of Life (QoL) [ Time Frame: Assessed frequently during the trial up to 66 months after Last Patient In ]
    Questionnaires to be completed by patients and collected frequently during the trial



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed written informed consent obtained prior to initiation of any study-specific procedures and treatment as confirmation of the patient's awareness and willingness to comply with the study requirements.
  2. Female patients ≥ 18 years with histologically confirmed primary advanced invasive high grade epithelial ovarian cancer, peritoneal cancer, or fallopian tube cancer FIGO III/IV (except FIGO stage IIIA2 without nodal involvement) according to recent FIGO classification (= FIGO stage IIIB - IV according to FIGO 2009 classification).
  3. All patients must have had either upfront primary debulking surgery OR plan to undergo chemotherapy with interval debulking surgery.
  4. Patients must have available tumor samples to be sent to central laboratory as formalin-fixed, paraffin-embedded (FFPE) sample for determination of BRCA status prior to randomization for stratification.
  5. Patients must be able to commence systemic therapy within 8 weeks of cytoreductive surgery.
  6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
  7. Estimated life expectancy > 3 months.
  8. Adequate bone marrow function (within 28 days prior to day 1, cycle 1)

    • Absolute Neutrophil Count (ANC) ≥ 1.5 x 10^9/L
    • Platelets (PLT) ≥ 100 x 10^9/L
    • Hemoglobin (Hb) ≥ 9 g/dL (can be post-transfusion)
  9. Adequate coagulation parameters (within 28 days prior to day 1, cycle 1)

    • Patients not receiving anticoagulant medication who have an International Normalized Ratio (INR) ≤ 1.5 and an Activated ProThrombin Time (aPTT) ≤ 1.5 x institutional upper limit of normal (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 institution medical standard) and the patient has been on a stable dose of anticoagulants for at least two weeks at the time of day 1, cycle 1.
  10. Adequate liver and kidney function (within 28 days prior to day 1, cycle 1)

    • Total bilirubin ≤ 1.5 x ULN (≤ 2.0 x ULN in patients with known Gilbert's syndrome) OR direct bilirubin ≤ 1.0 x ULN.
    • Aspartate aminotransferase / Serum Glutamic Oxaloacetic Transaminase (ASAT/SGOT) and Alanine aminotransferase / Serum Glutamic Pyruvate Transaminase (ALAT/SGPT) ≤ 2.5 x ULN, unless liver metastases are present, in case of liver metastases values must be ≤ 5 x ULN.
    • Urine dipstick for proteinuria < 2+. If urine dipstick is ≥ 2+, 24 hour urine must demonstrate ≤ 1 g of protein in 24 hours.
    • Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 30 mL/min using the Cockcroft-Gault equation.
  11. Patients must have normal blood pressure (BP) or adequately treated and controlled BP, with a systolic BP of ≤ 140 mmHg and diastolic BP of ≤ 90 mmHg for eligibility. Patients must have a BP of ≤ 140/90 mmHg taken in the clinic setting by a medical professional within 4 weeks prior to day 1, cycle 1.
  12. Negative urine or serum pregnancy test within 7 days prior to day 1, cycle 1 in women of childbearing potential (WOCBP), confirmed prior to treatment on day 1.
  13. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a highly effective contraceptive method with a failure rate of < 1% per year during the treatment period and for at least 6 months after administration of the last dose of medication.

    A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries, fallopian tubes, and/or uterus).

    Examples of contraceptive methods with a failure rate of < 1% per year include but are not limited to bilateral tubal ligation and/or occlusion, male sterilization, and intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.

  14. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, that include the completion of patient-reported outcomes questionnaires.

Exclusion Criteria:

  1. Non-epithelial tumor origin of the ovary.
  2. Ovarian tumors of low malignant potential (e.g. borderline tumors) and low grade tumors.
  3. Planned intraperitoneal cytotoxic chemotherapy.
  4. Malignancies other than ovarian cancer within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death (e.g., 5-year OS rate > 90%) and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, ductal carcinoma in situ of the breast, or stage I p53 wild type endometrial cancer).
  5. Prior systemic treatment for ovarian cancer.
  6. Prior treatment with Poly adenosine diphosphate ribose polymerase (PARP) inhibitor.
  7. Administration of other simultaneous chemotherapy drugs, any other anticancer therapy or anti-neoplastic hormonal therapy, or simultaneous radiotherapy during the trial treatment period (hormonal replacement therapy is permitted).
  8. Prior randomization in this trial.
  9. Major surgery within 1 week of starting study treatment or patient who has not completely recovered from the effects of any major surgery. Core biopsy or other minor surgical procedure within 7 days prior to day 1, cycle 1 is permitted.
  10. History or clinical suspicion of brain metastases or spinal cord compression. CT/MRI of the brain is mandatory (within 4 weeks prior to day 1, cycle 1) in case of suspected brain metastases. Spinal MRI is mandatory (within 4 weeks prior to day 1, cycle 1) in case of suspected spinal cord compression.
  11. Significant traumatic injury during 4 weeks preceding the potential first dose of bevacizumab.
  12. Previous Cerebro-Vascular Accident (CVA), Transient Ischemic Attack (TIA) or Sub-Arachnoids Hemorrhage (SAH) within 6 months prior to day 1, cycle 1.
  13. History or evidence of thrombotic or hemorrhagic disorders within 3 months prior to day 1, cycle 1.
  14. History or evidence upon neurological examination of central nervous system (CNS) disease, unless adequately treated with standard medical therapy e.g. uncontrolled seizures.
  15. Pregnant or lactating women.
  16. Treatment with any other investigational agent, or participation in another clinical trial testing a drug within 4 weeks or 5 times the half-life of the drug, whichever is longer, prior to day 1, cycle 1 or concomitantly with this trial.
  17. Known hypersensitivity to bevacizumab and its excipients, Chinese hamster ovary cell products or other recombinant human or humanized antibodies. Known hypersensitivity to niraparib, paclitaxel and carboplatin and its components or excipients.
  18. Non-healing wound, active ulcer or bone fracture. Patients with granulating incisions healing by secondary intention with no evidence of facial dehiscence or infection are eligible but require 3-weekly wound examinations.
  19. Clinically significant cardiovascular disease, including

    • Myocardial infarction or unstable angina within 6 months of day 1, cycle 1
    • New York Heart Association (NYHA) Grade 2 Congestive Heart Failure (CHF),
    • Poorly controlled cardiac arrhythmia despite medication (patients with rate-controlled atrial fibrillation are eligible)
    • Grade ≥ 3 peripheral vascular disease (i.e. symptomatic and interfering with activity of daily living (ADL) requiring repair or revision)
    • Significant vascular disease including aortic aneurysm requiring surgical repair
  20. Pre-existing sensory or motor neuropathy ≥ Grade 2.
  21. Any prior history of hypertensive crisis (CTCAE grade 4) or hypertensive encephalopathy.
  22. Patients with a history of or current Nephrotic syndrome.
  23. Bowel obstruction (including subocclusive disease).
  24. History of abdominal fistula or tracheoesophageal fistula or gastrointestinal perforation or active gastrointestinal bleeding or anastomotic insufficiency within 6 months of day 1, cycle 1.
  25. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of niraparib.
  26. Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contra-indicates the use of an investigational drug or puts the patient at high risk for treatment-related complications.
  27. Any known history or current diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
  28. Previous allogeneic bone marrow transplant or previous solid organ transplantation.
  29. Current or recent (within 10 days prior to day 1, cycle 1) chronic use of aspirin > 325 mg/day. Patients treated with other inhibitors of platelet aggregation such as clopidogrel, prasugrel, ticlopidine, tirofibane or dipyridamole should not be included into the trial.
  30. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. This includes also any psychiatric disorder that prohibits obtaining informed consent.
  31. Patient has known active hepatitis B or hepatitis C.
  32. Patient has a history of Posterior Reversible Encephalopathy Syndrome (PRES).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05009082


Contacts
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Contact: Sandra Polleis +49 611 880467 ext 40 spolleis@ago-ovar.de

Locations
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Germany
KEM Essen | Evang. Kliniken Essen-Mitte gGmbH Recruiting
Essen, Germany
Albertinen Krankenhaus Recruiting
Hamburg, Germany
Mammazentrum HH am Krankenhaus Jerusalem Not yet recruiting
Hamburg, Germany
Gynäkologisch-Onkologische Praxis am Pelikanplatz Not yet recruiting
Hannover, Germany
Städtisches Klinikum Karlsruhe Not yet recruiting
Karlsruhe, Germany
ViDia Christliche Kliniken Karlsruhe Not yet recruiting
Karlsruhe, Germany
Zentrum für ambulante gynäkologische Onkologie am HELIOS Klinikum Krefeld Not yet recruiting
Krefeld, Germany
Klinikum Ludwigsburg Not yet recruiting
Ludwigsburg, Germany
Klinikum Neumarkt Not yet recruiting
Neumarkt, Germany
MVZ Nordhausen Recruiting
Nordhausen, Germany
Thüringen-Kliniken "Georgius Agricola" Not yet recruiting
Saalfeld, Germany
Leopoldina Krankenhaus Schweinfurt Not yet recruiting
Schweinfurt, Germany
St. Josefs-Hospital Not yet recruiting
Wiesbaden, Germany
Sponsors and Collaborators
AGO Study Group
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Investigators
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Study Chair: Philipp Harter, MD, PhD KEM Essen | Evang. Kliniken Essen-Mitte gGmbH
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Responsible Party: AGO Study Group
ClinicalTrials.gov Identifier: NCT05009082    
Other Study ID Numbers: AGO-OVAR 28
2021-001271-16 ( EudraCT Number )
ENGOT-ov57 ( Other Identifier: European Network for Gynecological Oncological Trial groups )
First Posted: August 17, 2021    Key Record Dates
Last Update Posted: October 28, 2022
Last Verified: October 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AGO Study Group:
High Grade Epithelial Ovarian Cancer
Advanced Ovarian Cancer
Niraparib
Bevacizumab
Carboplatin
Paclitaxel
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Fallopian Tube Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Fallopian Tube Diseases
Paclitaxel
Bevacizumab
Carboplatin
Niraparib
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances