NCT05685836

Brief Summary

Bevacizumab can be an effective treatment for individuals with NF2 and improve different nerve functions (like hearing, tinnitus or balance problems) and the quality of life of NF2 patients. However, bevacizumab is not effective in all patients or all tumors, at the cost of moderate toxicity and considerable financial burden. Therefore, this observational study will validate an imaging biomarker method to predict bevacizumab efficacy in order to avoid adverse effects and high costs in non-responders to bevacizumab treatment. Patients will undergo standard-of-care treatment with the sole addition of a pre-treatment 89Zr-Bevacizumab PET/CT-scan. Per standard-of-care bevacizumab therapy is administered every three weeks for six months. To monitor treatment effect, follow-up is performed at 3-month intervals.

Trial Health

57
Monitor

Trial Health Score

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

Trial has exceeded expected completion date
Enrollment
15

participants targeted

Target at below P25 for all trials

Timeline
Completed

Started Oct 2022

Typical duration for all trials

Geographic Reach
1 country

1 active site

Status
recruiting

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

Study Start

First participant enrolled

October 20, 2022

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

December 5, 2022

Completed
1 month until next milestone

First Posted

Study publicly available on registry

January 17, 2023

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2024

Completed
Last Updated

March 20, 2024

Status Verified

March 1, 2024

Enrollment Period

2.2 years

First QC Date

December 5, 2022

Last Update Submit

March 19, 2024

Conditions

Neurofibromatosis 2

Keywords

neurofibromatosis 2NF2-related schwannomatosisvestibular schwannomabevacizumab89Zr-BevacizumabPET/CT imaginghearing

Outcome Measures

Primary Outcomes (18)

  • Hearing response (HR) - WRS

    Word Recognition Score (WRS), % at x dB

    Baseline

  • Hearing response (HR) - WRS

    Word Recognition Score (WRS), % at x dB

    3 months

  • Hearing response (HR) - WRS

    Word Recognition Score (WRS), % at x dB

    6 months

  • Hearing response (HR) - PTA

    Pure Tone Average (PTA), in dB

    Baseline

  • Hearing response (HR) - PTA

    Pure Tone Average (PTA), in dB

    3 months

  • Hearing response (HR) - PTA

    Pure Tone Average (PTA), in dB

    6 months

  • Radiographic response (RR) - tumor volumetry on MRI

    Size change in volumetric MRI (REiNS criteria); volumetry in mL or mm

    Baseline

  • Radiographic response (RR) - tumor volumetry on MRI

    Size change in volumetric MRI (REiNS criteria); volumetry in mL or mm

    3 months

  • Radiographic response (RR) - tumor volumetry on MRI

    Size change in volumetric MRI (REiNS criteria); volumetry in mL or mm

    6 months

  • Radiographic response (RR) - ADC

    Apparent diffusion coefficient (ADC) of tumor of interest, in mm2/s, on greatest diameter

    Baseline

  • Radiographic response (RR) - ADC

    Apparent diffusion coefficient (ADC) of tumor of interest, in mm2/s, on greatest diameter

    3 months

  • Radiographic response (RR) - ADC

    Apparent diffusion coefficient (ADC) of tumor of interest, in mm2/s, on greatest diameter

    6 months

  • Radiographic response (RR) - Microbleeds

    Location and number of microbleeds

    Baseline

  • Radiographic response (RR) - Microbleeds

    Location and number of microbleeds

    3 months

  • Radiographic response (RR) - Microbleeds

    Location and number of microbleeds

    6 months

  • Radiographic response (RR) - Diffusion restriction

    Diffusion restriction, yes / no

    Baseline

  • Radiographic response (RR) - Diffusion restriction

    Diffusion restriction, yes / no

    3 months

  • Radiographic response (RR) - Diffusion restriction

    Diffusion restriction, yes / no

    6 months

Secondary Outcomes (18)

  • Vestibular Function

    Baseline

  • Vestibular Function

    3 months

  • Vestibular Function

    6 months

  • Vestibular Function

    Baseline

  • Vestibular Function

    3 months

  • +13 more secondary outcomes

Study Arms (1)

Bevacizumab

After determining eligibility, all patients will undergo standard-of-care treatment with the sole addition of a pre-treatment 89Zr-Bevacizumab PET/CT-scan. Patients will first receive 5 mg 89Zr-Bevacizumab 4 days before PET/CT scan. This is followed by standard-of-care intravenous 7.5mg/kg bevacizumab (Avastin) therapy, administered every three weeks for six months

Drug: Bevacizumab Zirconium Zr-89

Interventions

Bevacizumab Zirconium Zr-89DRUG

See Arm description.

Also known as: Avastin, 89Zr-Bevacizumab, Bevacizumab
Bevacizumab

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Adult patients with a confirmed diagnosis of NF2 and candidate for bevacizumab therapy.

You may qualify if:

  • Patients aged 18 years or older
  • Confirmed diagnosis of NF2 by revised Manchester criteria
  • Provided written informed consent
  • Patients must have measurable disease, defined as at least one VS \> 0.4 ml (on volumetric analysis) that can be accurately measured by contrast-enhanced T1-weighted cranial MRI scan.
  • Eligible and planned for bevacizumab treatment

You may not qualify if:

  • Patients with a contra-indication for PET and MRI, such as pregnancy and metal elements.
  • Patients with a known allergy to substances used in this study
  • Concurrent treatment with Everolimus

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Leiden University Medical Center

Leiden, South Holland, 2333ZA, Netherlands

RECRUITING

MeSH Terms

Conditions

Neurofibromatosis 2Neuroma, Acoustic

Interventions

89Zr-bevacizumabBevacizumab

Condition Hierarchy (Ancestors)

NeurilemmomaNeuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeurofibromatosesNeurofibromaNerve Sheath NeoplasmsNeoplasms, Nerve TissueNeuromaNeoplastic Syndromes, HereditaryVestibulocochlear Nerve DiseasesRetrocochlear DiseasesEar DiseasesOtorhinolaryngologic DiseasesOtorhinolaryngologic NeoplasmsCranial Nerve NeoplasmsCranial Nerve DiseasesNervous System DiseasesNeurocutaneous SyndromesHeredodegenerative Disorders, Nervous SystemNeurodegenerative DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesNervous System NeoplasmsNeoplasms by SitePeripheral Nervous System Neoplasms

Intervention Hierarchy (Ancestors)

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

Study Officials

  • Hans AJ Gelderblom, MD, PhD

    Leiden University Medical Center

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Jules PJ Douwes, MD

CONTACT

715269111j.p.j.douwes@lumc.nl

Erik F Hensen, MD, PhD

CONTACT

715269111e.f.hensen@lumc.nl

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Prof. A.J. Gelderblom, MD, PhD, Head of Medical Oncology, Principal Investigator

Study Record Dates

First Submitted

December 5, 2022

First Posted

January 17, 2023

Study Start

October 20, 2022

Primary Completion

December 31, 2024

Study Completion

December 31, 2024

Last Updated

March 20, 2024

Record last verified: 2024-03

Locations

NL(1)