89Zr-Bevacizumab PET/CT Imaging in NF2 Patients

89Zr-Bevacizumab PET/CT Imaging of Vestibular Schwannomas for the Prediction of Bevacizumab Treatment Effect in Patients With Symptomatic Neurofibromatosis Type 2

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.

Study Overview

• Status: Recruiting
• Conditions: Neurofibromatosis 2
• Intervention / Treatment: Drug: Bevacizumab Zirconium Zr-89

• Study Type: Observational
• Enrollment (Estimated): 15

Contacts and Locations

• Study Contact: Name: Jules PJ Douwes, MD; Phone Number: +31 715269111; Email: j.p.j.douwes@lumc.nl
• Study Contact Backup: Name: Erik F Hensen, MD, PhD; Phone Number: +31 715269111; Email: e.f.hensen@lumc.nl

Study Locations

• Netherlands
  • Zuid-Holland
    • Leiden, Zuid-Holland, Netherlands, 2333ZA
      • Recruiting
      • Leiden University Medical Center
      • Contact: Jules PJ Douwes, MD; Phone Number: +31 715269111; Email: j.p.j.douwes@lumc.nl
      • Contact: Hans AJ Gelderblom, MD, PhD; Phone Number: +31 715269111; Email: a.j.gelderblom@lumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

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

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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; See Arm description.; Other Names: Avastin; Bevacizumab; 89Zr-Bevacizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vestibular Function	Video-Head Impulse Test (vHIT)	Baseline
Vestibular Function	Video-Head Impulse Test (vHIT)	3 months
Vestibular Function	Video-Head Impulse Test (vHIT)	6 months
Vestibular Function	cervical Vestibular Evoked Myogenic Potential (cVEMP) test	Baseline
Vestibular Function	cervical Vestibular Evoked Myogenic Potential (cVEMP) test	3 months
Vestibular Function	cervical Vestibular Evoked Myogenic Potential (cVEMP) test	6 months
Vestibular Function	Caloric test	Baseline
Vestibular Function	Caloric test	3 months
Vestibular Function	Caloric test	6 months
Patient reported outcome measures (PROM)	Questionnaire on Quality of Life, and presence of symptoms	Baseline
Patient reported outcome measures (PROM)	Questionnaire on Quality of Life, and presence of symptoms	3 months
Patient reported outcome measures (PROM)	Questionnaire on Quality of Life, and presence of symptoms	6 months
Physical examination	General neurological examination is performed to assess if the patient has neurological symptoms, if any. The examination is done according to standard clinical care and has a descriptive nature. Cranial nerve (dys)function, including House Brackmann scale for the facial nerve (n. VII) and trigeminal nerve function (n. V), including presence of neuralgia and hypoesthesia, are described in more detail.	Baseline
Physical examination	General neurological examination is performed to assess if the patient has neurological symptoms, if any. The examination is done according to standard clinical care and has a descriptive nature. Cranial nerve (dys)function, including House Brackmann scale for the facial nerve (n. VII) and trigeminal nerve function (n. V), including presence of neuralgia and hypoesthesia, are described in more detail.	3 months
Physical examination	General neurological examination is performed to assess if the patient has neurological symptoms, if any. The examination is done according to standard clinical care and has a descriptive nature. Cranial nerve (dys)function, including House Brackmann scale for the facial nerve (n. VII) and trigeminal nerve function (n. V), including presence of neuralgia and hypoesthesia, are described in more detail.	6 months
Renal function	Creatinine clearance (CrCl), eGFR (mL/minute, ref. >90)	Baseline
Renal function	Creatinine clearance (mmol/L), eGFR (mL/minute)	3 months
Renal function	Creatinine clearance (mmol/L), eGFR (mL/minute)	6 months

Collaborators and Investigators

• Sponsor: Leiden University Medical Center
• Investigators: Principal Investigator: Hans AJ Gelderblom, MD, PhD, Leiden University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2022
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: December 5, 2022
• First Submitted That Met QC Criteria: January 5, 2023
• First Posted (Actual): January 17, 2023

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: bevacizumab; hearing; vestibular schwannoma; PET/CT imaging; neurofibromatosis 2; NF2-related schwannomatosis; 89Zr-Bevacizumab
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Genetic Diseases, Inborn; Neuromuscular Diseases; Otorhinolaryngologic Neoplasms; Otorhinolaryngologic Diseases; Neurodegenerative Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Peripheral Nervous System Diseases; Ear Diseases; Nervous System Neoplasms; Heredodegenerative Disorders, Nervous System; Neoplastic Syndromes, Hereditary; Cranial Nerve Diseases; Neuroendocrine Tumors; Nerve Sheath Neoplasms; Neurocutaneous Syndromes; Peripheral Nervous System Neoplasms; Cranial Nerve Neoplasms; Neuroma, Acoustic; Neurilemmoma; Neuroma; Vestibulocochlear Nerve Diseases; Retrocochlear Diseases; Neurofibromatoses; Neurofibromatosis 1; Neurofibroma; Neurofibromatosis 2; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Radiopharmaceuticals; Bevacizumab; 89Zr-bevacizumab
• Other Study ID Numbers: NF2PET; 2020-000156-35 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No