AzTrials
AzTrials

Ovarian CancerPhase 1/2AVANOVANCT02354131

Niraparib Versus Niraparib-bevacizumab Combination in Women With Platinum-sensitive Epithelial Ovarian Cancer

A Phase 1/2 study testing Niraparib and Bevacizumab in people with Ovarian Cancer, run by Nordic Society of Gynaecological Oncology - Clinical Trials Unit at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Ovarian Cancer
What is being tested?
Niraparib and Bevacizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
108 participants
Where
2 sitesin 2 countries
Study dates
15 Feb 2015to 15 Dec 2021
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • A patient will be eligible for inclusion only if all of the following criteria are fulfilled:
  • 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.
Show all 31Show fewer
  • 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
  • Patients may have received a PARP inhibitor as first-line maintenance therapy.
  • Patients must have disease that is measurable according to RECIST or assessable according to the GCIG criteria
  • The patient agrees to complete PROs (QoL questionnaire) during study treatment AND at one additional time point 8 weeks following progression of disease
  • ECOG performance status 0-2
  • Adequate organ function
  • Absolute neutrophil count (ANC) ≥1,5 x 109/L
  • Platelets >100 x 109/L
  • Hemoglobin ≥ 9g/dl
  • Serum creatinine ≤1.5x upper limit of normal (ULN) or calculated creatinine clearance ≥50mL/min using Cockcroft-Gault formula
  • Total bilirubin ≤1.5x ULN
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5x ULN unless liver metastases are present, in which case they must be ≤5x ULN.
  • Able to take oral medications
  • Life expectancy of at least 12 weeks
  • Patients must fulfill all inclusions criteria and according to investigator fit to receive niraparib and/or bevacizumab.
  • Women of childbearing potential must use adequate birth control for the duration of study participation

Who cannot join

  • A patient will not be eligible for inclusion if any of the following criteria are fulfilled:
  • Ovarian sarcomas, small cell carcinoma with neuroendocrine differentiation, non-epithelial cancers and cancer types not mentioned in the inclusion criteria
  • 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
Show all 27Show fewer
  • 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
  • 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)
  • 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
  • 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.
  • Radiographic evidence of cavitation or necrotic tumors with invasion of adjacent major blood vessels
  • Active or chronic hepatitis C and/or B infection
  • Persistence of clinically relevant therapy related toxicity from previous chemotherapy
  • 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
  • Patients must not have any known history of MDS
  • Patients must not have known persistent (> 4 weeks) ≥ Grade 2 hematological toxicity from prior cancer therapy
  • Patients must not have known ≥ Grade 3 thrombocytopenia or anemia with the last chemotherapy regimen.

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

United States1 site

  • Massachusetts General Hospital

    Boston, Massachusetts

Other trials in United States

Denmark1 site

  • Rigshospitalet

    Copenhagen, Region Sjælland, 2100

Other trials in Denmark

About this study

Official title: Part 1: AVANOVA1 - A Phase I Study to Evaluate the Safety and Tolerability of Bevacizumab-niraparib Combination Therapy and Determine the Recommended Phase 2 Dose (RP2D) in Women With Platinum-sensitive Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer Part 2: AVANOVA2 - A Two-arm, Open-label, Phase II Randomized Study to Evaluate the Efficacy of Niraparib Versus Niraparib-bevacizumab Combination in Women With Platinum-sensitive Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer.

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.

Read more

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.

Read the detailed description

Part 1: This is a single-centre, phase 1a, open-label, dose-escalation study to evaluate the safety and tolerability of bevacizumab-niraparib combination and determine the RP2D in patients with platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal cancer.

The standard 3+3 design will be used. Part 2: (n=94) This multicenter, prospective, open-label, randomized phase 2 study is evaluating the efficacy of niraparib against niraparib-bevacizumab combination in Women with platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal cancer.

Stratification: Patients are stratified according to:

  1. HRD status (positive/negative)
  2. Treatment-Free interval to prior therapy (6-12 months > 12 months) Randomization: 1:1 randomization

Study arms: Patients are randomized to one of the two treatment arms:

Arm 1: Niraparib monotherapy until progression. Arm 2: Niraparib-bevacizumab combination therapy until progression.

Conditions
Ovarian Cancer
Being tested
Niraparib, Bevacizumab
Keywords
Ovarian cancer, Niraparib, Bevacizumab, PARP, Phase 2 randomized
Medical subject headings
Ovarian Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02354131
Study groupRoleWhat they receive
Niraparib monotherapyExperimentalNiraparib mono therapy until progression
Receives: Drug: Niraparib
Niraparib-bevacizumab combinationExperimentalNiraparib-bevacizumab combination therapy until progression
Receives: Drug: Niraparib; Drug: Bevacizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression free survival

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

    Measured: 30 months

Secondary outcomes (1)

  1. Disease Control Rate

    Measured: 30 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Feb 2015 (estimated)
  2. Study start15 Feb 2015
  3. Primary completion15 Nov 2018
  4. Study completion15 Dec 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
108 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02354131
Sponsor's protocol ID
ENGOT-OV24-NSGO/AVANOVA
Acronym
AVANOVA
Status last verified
Aug 2022
First submitted
25 Jan 2015
Last updated
30 Aug 2022
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 38427930

  • 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.

    PubMed 37185961

  • 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.

    PubMed 31474354

  • 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.

    PubMed 31375879

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Niraparib and Bevacizumab in people with Ovarian Cancer, run by Nordic Society of Gynaecological Oncology - Clinical Trials Unit at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 31 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States, Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression free survival (time frame: 30 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02354131, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Aug 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in