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Trial Comparing Niraparib-bevacizumab-TSR042 and Niraparib-bevacizumab to Standard of Care in Recurrent Ovarian Cancer

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ClinicalTrials.gov Identifier: NCT03806049
Recruitment Status : Not yet recruiting
First Posted : January 16, 2019
Last Update Posted : January 16, 2019
Sponsor:
Information provided by (Responsible Party):
Nordic Society for Gynaecologic Oncology

Tracking Information
First Submitted Date  ICMJE January 13, 2019
First Posted Date  ICMJE January 16, 2019
Last Update Posted Date January 16, 2019
Estimated Study Start Date  ICMJE June 2019
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 15, 2019)
Progression-free Survival [ Time Frame: 42 months ]
the time from randomization until the date of the first objective radiological disease progression according to investigator assessment of RECIST v1.1 or death by any cause, whichever occurs first.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: January 15, 2019)
Progression Free Survival in Sub-Population in months [ Time Frame: 42 months ]
the time from randomization until the date of the first objective radiological disease progression according to investigator assessment of RECIST v1.1 or death by any cause, whichever occurs first for the predefined study subgroups.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Trial Comparing Niraparib-bevacizumab-TSR042 and Niraparib-bevacizumab to Standard of Care in Recurrent Ovarian Cancer
Official Title  ICMJE ENGOT-OV42-NSGO/AVANOVA-Triplet: A Randomized Study to Evaluate the Efficacy of Niraparib-bevacizumab-TSR042 Triplet Against Niraparib-bevacizumab Doublet and Against Standard of Care in Women With Platinum-sensitive Ovarian Cancer
Brief Summary NSGO / AVANOVA-Triplet: This three-arm randomized trial is to demonstrate efficacy of niraparib-bevacizumab-TSR-042 triplet combination against standard of care treatment and to demonstrate efficacy of niraparib-bevacizumab-TSR-042 triplet combination against niraparib-bevacizumab doublet combination for patients with platinum-sensitive epithelial ovarian, fallopian tube, or peritoneal cancer
Detailed Description This is a multicenter randomized open-label trial to compare two different chemotherapy-free arms against standard of care treatment in patients with recurrent ovarian cancer with >6 months of chemotherapy-free interval to prior therapy.
Study Type  ICMJE Interventional
Study Phase Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
randomized, open-label, three arm study
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Ovarian Cancer
Intervention  ICMJE
  • Drug: Niraparib
    given orally once daily
    Other Name: Zejula
  • Drug: Bevacizumab
    given as iv infusion every three weeks
    Other Name: Avastin
  • Drug: TSR042
    Given as IV infusion every three weeks
  • Drug: Carboplatin
    given as iv infusion every three weeks
  • Drug: Paclitaxel
    given as iv infusion every three weeks
Study Arms
  • Experimental: A: triplet
    chemotherapy-free combination of niraprib + bevacizumab + TSR042
    Interventions:
    • Drug: Niraparib
    • Drug: Bevacizumab
    • Drug: TSR042
  • Experimental: B: Doublet
    chemotherapy-free combination of niraparib + bevacizumab
    Interventions:
    • Drug: Niraparib
    • Drug: Bevacizumab
  • Active Comparator: C: standard of care
    Standard of care chemotherapy: Carboplatin + paclitaxel
    Interventions:
    • Drug: Carboplatin
    • Drug: Paclitaxel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: January 15, 2019)
337
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date June 2024
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Recurrent platinum-sensitive epithelial ovarian, fallopian tube, or peritoneal cancer (platinum sensitivity defined as no recurrence within 6 months of last receipt of platinum/chemotherapy).
  2. High-grade serious or high-grade endometrioid histology or any histology with known BRCA mutation.
  3. Patient consents to perform BRCA test, and PD-L1 expression.
  4. Prior line of therapy: Patients must have received platinum-containing therapy for primary disease.
  5. No limits on number of platinum-based therapies.
  6. Up to one non-platinum-based line of therapy in recurrent setting is allowed.
  7. Patients may have received bevacizumab (or other anti-VEGF therapy) prior to entering in the trial.
  8. Patients may have participated in a PARP inhibitor maintenance trial or have received maintenance PARP inhibitor therapy are allowed, though it is necessary to unblind patient in order to correctly stratify. Patients who received a PARP inhibitor as definitive are not eligible. Patients may have participated in a trial containing immune-checkpoint inhibitor.
  9. Target group: Age 18+
  10. Histological confirmed ovarian, fallopian tube or peritoneal cancers
  11. Patients must give informed consent
  12. Patients may have undergone primary or interval debulking surgery
  13. Patients may have received bevacizumab or other anti-angiogenic therapy
  14. Patients may have received a PARP inhibitor as first-line maintenance therapy.
  15. Patients must have disease that is measurable according to RECIST or assessable according to the GCIG criteria
  16. The patient agrees to complete PROs (QoL questionnaire) during study treatment AND at one additional time point 8 weeks following progression of disease
  17. ECOG performance status 0-2
  18. Adequate organ function

    1. Absolute neutrophil count (ANC) ≥1,5 x 109/L
    2. Platelets >100 x 109/L
    3. Hemoglobin ≥ 9g/dl
    4. Serum creatinine ≤1.5x upper limit of normal (ULN) or calculated creatinine clearance ≥50mL/min using Cockcroft-Gault formula
    5. Total bilirubin ≤1.5x ULN
    6. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5x ULN unless liver metastases are present, in which case they must be ≤5x ULN.
  19. Able to take oral medications
  20. Life expectancy of at least 12 weeks
  21. Patients must fulfill all inclusions criteria and according to investigator fit to receive niraparib, bevacizumab and TSR042.
  22. Women of childbearing potential must use adequate birth control for the duration of study participation -

Exclusion Criteria:

Ovarian sarcomas, small cell carcinoma with neuroendocrine differentiation, non-epithelial cancers and cancer types not mentioned in the inclusion criteria 2. Concurrent cancer therapy 3. Concurrent treatment with an investigational agent or participation in another clinical trial 4. Major injuries or surgery within the past 21 days prior to start of study treatment with incomplete wound healing and/or planned surgery during the on-treatment study period 5. Previous malignant disease: patients are not eligible for the study if diagnosis, detection or treatment of invasive cancer (other than ovarian cancer; with the exception of basal or squamous cell carcinoma of the skin that was definitively treated) was detected within 2 years prior to randomization 6. Active infections or other serious underlying significant medical illness, abnormal laboratory finding or psychiatric illness/social situation that would, in the Investigator's judgment, makes the patient inappropriate for this study 7. Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug 8. History of bowel obstruction, including sub-occlusive disease, related to the underlying disease and history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess. Evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction 9. Known contraindications to PARP inhibitors, VEGF directed therapy or immune checkpoint inhibitors 10. Known uncontrolled hypersensitivity to the investigational drugs 11. History of major thromboembolic event defined as:

  • Uncontrolled pulmonary embolism (PE)
  • Deep venous thrombosis (DVT)
  • Other related conditions, though patients with stable therapeutic anticoagulation for more than three months prior randomization are eligible for this study. This also apply to PE & DVT.

    12. History of a cerebral vascular accident, transient ischemic attack or subarachnoid hemorrhage within the past 3 months 13. History of clinically significant hemorrhage in the past 3 months 14. Uncontrolled and/or symptomatic CNS metastasis or leptomeningeal carcinomatosis (Dexamethasone/prednisone therapy will be allowed if administered as stable dose for at least one month prior randomization) 15. Significant cardiovascular diseases, including uncontrolled hypertension, clinically relevant cardiac arrhythmia, unstable angina or myocardial infarction within 6 months prior to randomization, congestive heart failure > NYHA III, severe peripheral vascular disease, QT prolongation >470 msec ,clinically significant pericardial effusion 16. Pregnancy or breastfeeding. Patients with preserved reproductive capacity, unwilling to use a medically acceptable method of contraception for the duration of the trial and for 3 months afterwards.

    17. Radiographic evidence of cavitation or necrotic tumors with invasion of adjacent major blood vessels 18. Active or chronic hepatitis C and/or B infection 19. Persistence of clinically relevant therapy related toxicity from previous chemotherapy 20. Proteinuria as demonstrated by: (a) urine protein: creatinine (UPC) ratio >/= 1.0 at screening OR (b) urine dipstick for proteinuria >/=2+ (patients discovered to have >/=2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hr urine collection and must demonstrate </=1g of protein in24 hours to be eligible 21. Patients must not have any known history of MDS 22. Patients must not have known persistent (> 4 weeks) ≥ Grade 2 hematological toxicity from prior cancer therapy 23. Patients must not have known ≥ Grade 3 thrombocytopenia or anemia with the last chemotherapy regimen.

Sex/Gender
Sexes Eligible for Study: Female
Ages 18 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE
Contact: Mansoor R Mirza, MD 35459624 mansoor@rh.regionh.dk
Listed Location Countries  ICMJE Denmark,   Finland,   Norway
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03806049
Other Study ID Numbers  ICMJE NSGO/AVANOVA-Triplet
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Plan Description: All individual participant data will be anonymized
Responsible Party Nordic Society for Gynaecologic Oncology
Study Sponsor  ICMJE Nordic Society for Gynaecologic Oncology
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: MANSOOR RAZA R MIRZA NSGO
PRS Account Nordic Society for Gynaecologic Oncology
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP