GlioblastomaNEXTFRONTIERNCT06623565
Extensive Resection of Malignant Brain Tumors Using Advanced Imaging Techniques
A study testing Multimodal image-guided resection in people with Glioblastoma and Astrocytoma, IDH-Mutant, Grade 4, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
Trial summary
Rationale: Patients with IDH-wildtype glioblastoma or grade IV IDH-mutant astrocytoma have a very poor prognosis despite standard treatment consisting of surgery, radiotherapy, and chemotherapy. Diffuse infiltration of the brain by the tumor is thought to be one of the main causes of this therapy-resistance. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, Astrocytoma, IDH-Mutant, Grade 4
- What is being tested?
- Multimodal image-guided resection
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Apr 2024to Apr 2027
- Phase
- Interventional
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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- New clinical and radiological suspected diagnosis of IDH-wildtype glioblastoma or grade IV IDH-mutant astrocytoma
- Visible FET PET uptake in the tumor as assessed by the nuclear physician
- Indication for a surgical resection and adjuvant treatment according to the neuro oncology multidisciplinary meeting
- Eligible for a supramarginal resection according to two neurosurgeons in consensus
- Karnofsky Performance Score (KPS) ≥ 70.
Who cannot join
- Previous brain surgery or cranial radiotherapy
- No significant other brain pathology, in the opinion of the PI or designee, such as multiple sclerosis, neurodegenerative disease, stroke
- Tumor located infratentorially or in the spinal cord
- Lack of adequate social or family support needed for adherence to the further postoperative therapeutic regimen
- Pregnancy
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Amsterdam UMC location VUmc
Amsterdam, North Holland, 1081HV
Niels Verburg, MD PhD, +31204445013, n.verburg@amsterdamumc.nl
Niels Verburg, MD PhD
About this study
Official title: Multimodal Image-guided Resection of IDH Wildtype Glioblastoma and Grade IV IDH-mutant Astrocytoma
Rationale: Patients with IDH-wildtype glioblastoma or grade IV IDH-mutant astrocytoma have a very poor prognosis despite standard treatment consisting of surgery, radiotherapy, and chemotherapy. Diffuse infiltration of the brain by the tumor is thought to be one of the main causes of this therapy-resistance. In order to improve the surgical treatment, tumor regions with lower infiltration percentages need to be identified and resected during surgery, a so-called supramarginal resection. Currently, pre-operative T1 contrast enhanced weighted (T1c) MRI is used to identify the tumor for resection. We recently found the combination of apparent diffusion coefficient MRI and O-(2-[ 18F]fluoroethyl-)-L-tyrosine positron emission tomography (ADC/FET) to be significantly more accurate than T1c MRI alone in the detection of tumor infiltration. This makes ADC/FET a suitable candidate to guide supramarginal resection. Since FET PET is not as accessible and widely available as MRI, identification of an MRI based alternative could result in a more widespread implementation. Amide proton transfer chemical exchange saturation transfer (APT-CEST) MRI is a novel potential alternative for FET PET, since both measures are related to protein content.
Objective: In this project we aim to develop a safe and effective technique for ADC/FET guided resection of IDH-wildtype glioblastoma and grade IV IDH-mutant astrocytoma. The safety concerns neurological deficits and time to start of adjuvant therapy, while the effectiveness is aimed at the extent of resection. Our secondary aim is to evaluate the diagnostic accuracy of APT-CEST MRI and to assess whether APT-CEST MRI can serve as an alternative for FET PET for the detection of tumor infiltration.
Read more
Study design: prospective observational intervention study
Study population: 30 patients with clinical and radiological diagnosis of an untreated high grade glioma (suspected for glioblastoma (IDH wildtype) or grade IV astrocytoma (IDH mutant)), who are eligible for a supramarginal surgical resection and adjuvant treatment according two neurosurgeons in consensus and who are in relatively good condition (Karnofsky Performance Score (KPS) ≥70).
Intervention (if applicable): supramarginal ADC/FET-guided resection. To make sure that the standard treatment is always guaranteed, T1c MRI abnormalities will be included in the surgical target.
Main study parameters/endpoints: the main study endpoint is the optimization of ADC/FET-guided resection. Volumetric and percentual extent of resection, as measured with MRI and PET imaging, combined with surgery-induced morbidity will be used as outcome parameters. The secondary study parameters will be the histopathology-based diagnostic accuracy of APT-CEST MRI in comparison with FET PET, cognitive performance over time and progression free survival.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: participants will undergo pre- and postoperative MRI scanning. This is also part of regular clinical care, except there are additional MRI sequences including APT CEST in the pre-operative and pre-radiotherapy MRI. There are no risks associated with MRI acquisition after MRI safety screening. Participants will furthermore undergo a pre- and postoperative FET PET. The risks associated with PET scanning are limited, and the radiation burden will remain below 10 mSv (ICRP62 category intermediate risk (level IIb)). During surgery, biopsies are performed from areas that will be resected, so these biopsies will not introduce any extra risk. A potential benefit is the possibility of the removal of more tumor tissue. A potential risk is the additional removal of healthy brain tissue with the risk of neurological damage, which is controlled by pre- and intraoperative techniques such as visualization of white matter tracts and mapping (both asleep and awake) of critical functions such as language and control of strength.
- Conditions
- Glioblastoma, Astrocytoma, IDH-Mutant, Grade 4
- Being tested
- Multimodal image-guided resection
- Keywords
- multimodal imaging, high grade glioma, glioblastoma, supramarginal, resection, surgery
- Medical subject headings
- Glioblastoma, Astrocytoma, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Multimodal image-guided resectionProcedure or surgery
Supramarginal resection using combination of ADC MRI and FET PET
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Experimental | Supramarginal resection using combination of ADC MRI and FET PET Receives: Procedure: Multimodal image-guided resection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Extent of resection
Volumetric and percentual on pre-radiotherapy PET-MRI
Measured: within 4 weeks after surgery
Neurological functioning
Neurological Assessment in Neuro-Oncology (NANO) score
Measured: 3 months after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2024
- Study start1 Apr 2024
- Primary completionApr 2026 (estimated)
- Study completionApr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, dr. Niels Verburg, Amsterdam UMC, location VUmc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06623565
- Sponsor's protocol ID
- 2023.0020
- Other IDs
- CCA2021-5-27
- Acronym
- NEXTFRONTIER
- Status last verified
- Sep 2024
- First submitted
- 30 Sep 2024
- Last updated
- 2 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided