NCT02354131

Brief Summary

Part 1 (Phase 1): safety and tolerability of bevacizumab-Niraparib combination Part 2 (Randomized Phase 2): to compare Progression-Free Survival (PFS) PARP inhibitors are active as monotherapy to treat patients with recurrent ovarian cancer; the strongest activity being observed in the platinum sensitive, gBRCAmut subgroup as well as in gBRCAwt, HRD population but also in HRD negative disease. In the same population there is level one evidence that bevacizumab is beneficial. And a phase two randomized study has indicated that combination of a PARP inhibitor with anti-angiogenic drug is superior to PARP inhibitor alone. The question is: Is niraparib combined with bevacizumab superior to niraparib? The comparison of tolerability and efficacy of niraparib-bevacizumab combination against niraparib.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
108

participants targeted

Target at P75+ for phase_1 ovarian-cancer

Timeline
Completed

Started Feb 2015

Longer than P75 for phase_1 ovarian-cancer

Geographic Reach
2 countries

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 25, 2015

Completed
9 days until next milestone

First Posted

Study publicly available on registry

February 3, 2015

Completed
12 days until next milestone

Study Start

First participant enrolled

February 15, 2015

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 15, 2018

Completed
3.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 15, 2021

Completed
Last Updated

August 30, 2022

Status Verified

August 1, 2022

Enrollment Period

3.8 years

First QC Date

January 25, 2015

Last Update Submit

August 29, 2022

Conditions

Ovarian Cancer

Keywords

Ovarian cancerNiraparibBevacizumabPARPPhase 2 randomized

Outcome Measures

Primary Outcomes (1)

  • Progression free survival

    This is pick the winer trial. The best arm will be used for phase 3 trial against standard of care.

    30 months

Secondary Outcomes (1)

  • Disease Control Rate

    30 months

Study Arms (2)

Niraparib monotherapy

EXPERIMENTAL

Niraparib mono therapy until progression

Drug: Niraparib

Niraparib-bevacizumab combination

EXPERIMENTAL

Niraparib-bevacizumab combination therapy until progression

Drug: NiraparibDrug: Bevacizumab

Interventions

NiraparibDRUG

Niraparib versus Bevacizumab-Niraparib combo

Niraparib monotherapyNiraparib-bevacizumab combination
BevacizumabDRUG
Niraparib-bevacizumab combination

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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).
  • High-grade serious or high-grade endometrioid histology.
  • Patient consents to perform HRD test.
  • Patients with known BRCA status: BRCA positive patients must submit the tissue for HRD test, though these patients need not to wait for HRD test results and can be randomized in HRD positive stratum.
  • If tumor tissue is not sufficient to perform HRD test: these patients shall be randomized in HRD negative stratum as HRD unknown.
  • Prior line of therapy: Patients must have received platinum-containing therapy for primary disease.
  • No limits on number of platinum-based therapies. Population of patients who has previously received ≥ 3 lines of therapy for relapsed disease will be capped at 40%.
  • Up to one non-platinum-based line of therapy in recurrent setting.
  • Patients who are treated with bevacizumab just prior to entering in the trial must not have progressed under or within 3 months after bevacizumab.
  • Patients may have participated in a PARP inhibitor trial as first-line maintenance therapy and have not progressed within 3 months after PARP/placebo. Patients who received PARP inhibitor after relapse (definitive or maintenance therapy) are not eligible.
  • Target group: Age 18+
  • Histological confirmed ovarian, fallopian tube or peritoneal cancers
  • Patients must give informed consent
  • Patients may have undergone primary or interval debulking surgery
  • Patients may have received bevacizumab though no other prior use of anti-angiogenic therapy
  • +14 more criteria

You may not qualify if:

  • Concurrent cancer therapy
  • Concurrent treatment with an investigational agent or participation in another clinical trial
  • 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
  • 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
  • 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
  • Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug
  • 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
  • Known contraindications to PARP inhibitors or VEGF directed therapy
  • Known uncontrolled hypersensitivity to the investigational drugs
  • 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.
  • History of a cerebral vascular accident, transient ischemic attack or subarachnoid hemorrhage within the past 3 months
  • History of clinically significant hemorrhage in the past 3 months
  • +10 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, United States

Location

Rigshospitalet

Copenhagen, Region Sjælland, 2100, Denmark

Location

Related Publications (4)

  • Korsholm LM, Kjeldsen M, Perino L, Mariani L, Nyvang GB, Kristensen E, Bagger FO, Mirza MR, Rossing M. Combining Homologous Recombination-Deficient Testing and Functional RAD51 Analysis Enhances the Prediction of Poly(ADP-Ribose) Polymerase Inhibitor Sensitivity. JCO Precis Oncol. 2024 Feb;8:e2300483. doi: 10.1200/PO.23.00483.

    PMID: 38427930DERIVED

  • Gaitskell K, Rogozinska E, Platt S, Chen Y, Abd El Aziz M, Tattersall A, Morrison J. Angiogenesis inhibitors for the treatment of epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Apr 18;4(4):CD007930. doi: 10.1002/14651858.CD007930.pub3.

    PMID: 37185961DERIVED

  • Mirza MR, Avall Lundqvist E, Birrer MJ, dePont Christensen R, Nyvang GB, Malander S, Anttila M, Werner TL, Lund B, Lindahl G, Hietanen S, Peen U, Dimoula M, Roed H, Or Knudsen A, Staff S, Krog Vistisen A, Bjorge L, Maenpaa JU; AVANOVA investigators. Niraparib plus bevacizumab versus niraparib alone for platinum-sensitive recurrent ovarian cancer (NSGO-AVANOVA2/ENGOT-ov24): a randomised, phase 2, superiority trial. Lancet Oncol. 2019 Oct;20(10):1409-1419. doi: 10.1016/S1470-2045(19)30515-7. Epub 2019 Aug 29.

    PMID: 31474354DERIVED

  • Mirza MR, Bergmann TK, Mau-Sorensen M, Christensen RD, Avall-Lundqvist E, Birrer MJ, Jorgensen M, Roed H, Malander S, Nielsen F, Lassen U, Brosen K, Bjorge L, Maenpaa J. A phase I study of the PARP inhibitor niraparib in combination with bevacizumab in platinum-sensitive epithelial ovarian cancer: NSGO AVANOVA1/ENGOT-OV24. Cancer Chemother Pharmacol. 2019 Oct;84(4):791-798. doi: 10.1007/s00280-019-03917-z. Epub 2019 Aug 2.

    PMID: 31375879DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

niraparibBevacizumab

Condition Hierarchy (Ancestors)

Endocrine Gland NeoplasmsNeoplasms by SiteNeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Neoplasms, FemaleUrogenital NeoplasmsGenital DiseasesEndocrine System DiseasesGonadal Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Mansoor R Mirza, MD

    Nordic Society of Gynaecological Oncology - Clinical Trials Unit

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 25, 2015

First Posted

February 3, 2015

Study Start

February 15, 2015

Primary Completion

November 15, 2018

Study Completion

December 15, 2021

Last Updated

August 30, 2022

Record last verified: 2022-08

Locations

US(1)DK(1)