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AzTrials

GliomaNCT06381726

Personalized Rendering of Motor System Functional Plasticity Potential to Improve Glioma Resection and Quality of Life

A study testing Resting State Functional Magnetic Resonance Imaging (rs-fMRI), Up-front Motor Rehabilitation and Up-front Chemotherapy in people with Glioma and Glioma, Malignant, run by University of Milan at 1 site in Italy.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

Background Lower-grade-gliomas affect young patients, thus the longest progression-free-survival (PFS) with a high level quality of life is crucial. Surgery most significantly impacts on tumor natural history, postponing recurrence, improving symptoms, decreasing the need of adjuvant therapies, with extent of… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Glioma, Glioma, Malignant
What is being tested?
Resting State Functional Magnetic Resonance Imaging (rs-fMRI), Up-front Motor Rehabilitation and Up-front Chemotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
400 participants
Where
1 siteItaly
Study dates
7 Mar 2024to 28 Feb 2028
Phase
Interventional
Are there results?
Not yet: the study is under way

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

  • Patients signing informed consent for participation in the study
  • Males and females
  • Age ≥ 18 years
  • Patients with lower-grade gliomas with involvement of the motor pathways who are candidates for surgery
  • Patients signing informed consent for participation in the study
  • Males and females
  • Age ≥ 18 years
  • Patients with lower-grade gliomas treated over two years with tumors only biopsied and/or partially resected and eligible for second surgery

Who cannot join

  • Age <18 years
  • Inability to adhere to standard study controls
  • Subjects unable to understand and freely provide consent to the study

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Lorenzo Bello, MD contact

0039-340-217-1453

lorenzo.bello@unimi.it

Italy1 site, 1 recruiting

  • IRCCS Ospedale Galeazzi Sant'Ambrogio

    Milan, Lombardy, 20157

    Lorenzo Bello, MD, 0039-340-217-1453, lorenzo.bello@unimi.it

    Recruiting

Other trials in Italy

About this study

Background Lower-grade-gliomas affect young patients, thus the longest progression-free-survival (PFS) with a high level quality of life is crucial. Surgery most significantly impacts on tumor natural history, postponing recurrence, improving symptoms, decreasing the need of adjuvant therapies, with extent of resection, gross-total and supra-total (GTR and STR), strongly associating with longest PFS. Achievement of GTR or STR depends on the degree of functional reorganization induced by glioma. Consequently, a successful treatment fostering neural circuit reorganization before surgery, would increase the chance of GRT/STR.

Hypothesis The plastic potential of motor system suggests that reorganization of circuits controlling hand movements could be presurgically fostered in LGG patients by enhancing plasticity with up-front motor-rehabilitation and/or by decreasing tumor infiltration with up-front chemotherapy. Advanced neuroimaging allows to infer the neuroplasticity potential. Intraoperative assessment of the motor circuits functionality will validate reliability of preoperative analyses.

Read more

Aims The project has 4 aims, investigating: A) the presurgical functional (FC) and structural (SC) connectomics of the hand-motor network to picture the spontaneous reorganization and the influence of clinical, imaging and histomolecular variables; B) the dynamic of FC and SC after tumor resection; C) changes in FC and SC maps after personalized upfront motor rehabilitation and/or chemotherapy; D) the effect of FC and SC upfront treatment on the achievement of GTR/STR preserving hand dexterity.

Experimental Design Resting-state fMRI and diffusion-MRI will provide FC and SC maps pre- and post-surgery; personalized up-front motor rehabilitation and/or chemotherapy will be administered; Intraoperative brain mapping procedures will generate data to validate the maps.

Expected Results

  1. Provide a tool to render the motor functional reorganization predictive of surgical outcome.
  2. Identify demographic, clinical and imaging variables associated with functional reorganization.
  3. Describe the gain induced by up-front treatment.
  4. Distinguish "patterns" predicting chance for GTR/STR from "patterns" suggesting need for up-front treatment.

Impact On Cancer Results will increase the achievement of GTR/STR, preserving motor integrity, with dramatic impact on LGGs natural history.

Being tested
Resting State Functional Magnetic Resonance Imaging (rs-fMRI), Up-front Motor Rehabilitation, Up-front Chemotherapy
Keywords
Glioma, Neurosurgery, Chemotherapy, Neoadjuvant, Motor Rehabilitation, Magnetic Resonance Imaging, Diffusion Magnetic Resonance Imaging, Resting State Functional Magnetic Resonance Imaging, Functional Magnetic Resonance Imaging, Functional Connectomics, Structural Connectomics, Neuronal Plasticity, Higher Nervous Activity, Neurological Rehabilitation, Antineoplastic Protocols
Medical subject headings
Glioma

What participants receive

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

  • Resting State Functional Magnetic Resonance Imaging (rs-fMRI)Diagnostic test

    rs-fMRI + neurological and neuropsychological evaluation at preoperative timepoint and 1-2 months postop, 3-4 months postop, 6-8 months postop, 12 months postop

  • Up-front Motor RehabilitationBehavioural

    personalized motor rehabilitation for 6 months + rs-fMRI + neurological and neuropsychological evaluation before starting motor rehabilitation, at 2-3 months during rehabilitation, 6-9 months during rehabilitation, before surgery (if surgery indicated by tumour board), 1 month postop, 2-3 months postop

  • Up-front ChemotherapyDrug

    Temozolomide at either 6 cycles consisting of 150-200 mg per square meter for 5 days during each 28-day cycle, or metronomic schedule, + rs-fMRI + neurological and neuropsychological evaluation before starting motor rehabilitation, at 2-3 months during rehabilitation, 6-9 months during rehabilitation, before surgery (if surgery indicated by tumour board), 1 month postop, 2-3 months Post

Study groups in NCT06381726
Study groupRoleWhat they receive
Spontaneous motor reorganization: observationActive comparatorOnly neurological and neuropsychological assessment as per normal clinical routine and conventional and advanced functional, resting-state MRI acquisitions
Receives: Diagnostic Test: Resting State Functional Magnetic Resonance Imaging (rs-fMRI)
Enhanced motor reorganization: upfront Motor RehabilitationExperimentalPatients submitted to motor rehabilitation program aimed at learning unimanual and bimanual coordinated sequences, along with personalized exercise according to tumor location (frontal vs parietal). For 6 months each patient will perform the motor training program in outpatient training session, checked by a physiotherapist for corrected execution at home 3 times/week, and is assessed for the correct training execution and progresses in training sessions each month, by physical therapists at the Rehabilitation Unit and on a weekly schedule by on-line distant monitoring (telemedicine).
Receives: Behavioral: Up-front Motor Rehabilitation
Enhanced motor reorganization: upfront ChemotherapyExperimentalTemozolomide-based regimen of 6 months duration is applied. Treatment will be discontinued in case of toxicity (G2-G4).
Receives: Drug: Up-front Chemotherapy
Enhanced motor reorganization: upfront Chemotherapy + Motor RehabilitationExperimentalTemozolomide-based regimen of 6 months duration is applied. Treatment will be discontinued in case of toxicity (G2-G4). Patients will also be submitted to motor rehabilitation program aimed at learning unimanual and bimanual coordinated sequences, along with personalized exercise according to tumor location (frontal vs parietal). For 6 months each patient will perform the motor training program in outpatient training session, checked by a physiotherapist for corrected execution at home 3 times/week, and is assessed for the correct training execution and progresses in training sessions each month, by physical therapists at the Rehabilitation Unit and on a weekly schedule by on-line distant monitoring (telemedicine).
Receives: Behavioral: Up-front Motor Rehabilitation; Drug: Up-front Chemotherapy

What is being measured

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

  1. Muscle power

    MRC Muscle power assessment (0-5)

    Measured: ARM 1: preop, 1-2 months postop, 3-4 months postop, 6-8 months postop, 12 months postop; ARM 2/3/4: before starting treatment, at 2-3 and 6-9 months during treatment, before surgery (if indicated), 1 month postop, 2-3 months postop

  2. Motor praxia

    ARAT test (Grasp, Grip, Pinch, each consisting of 3 items scoring 0 [not performed, 1/2 abnormal, 3 ok]), De Renzi test (24 complex gestures with individual scoring 0-3 [0 no execution/always abnormal, 2/1 ok after 1 or 2 trials, 3 ok] each evaluating one or more among finger movements [total score 0-36], hand movements [total score 0-36], hand and finger position [total score 0-36], sequence of movements [total score 0-36], meaningful gestures [total score 0-36], meaningless gestures [total score 0-36]; tool pantomime for 10 objects individual score 0 if always incorrect, 1 if correct after command repetition, 2 correct immediately, total score range 0-20)

    Measured: ARM 1: preop, 1-2 months postop, 3-4 months postop, 6-8 months postop, 12 months postop; ARM 2/3/4: before starting treatment, at 2-3 and 6-9 months during treatment, before surgery (if indicated), 1 month postop, 2-3 months postop

Secondary outcomes (1)

  1. Comprehensive neuropsychological assessment

    Language: Naming test; Fhonemic and Semantic Fluency Verbal and Spatial Memory: 15 Rey's Words; Recall Rey figure; Visuo-spatial test: Rey's Copy; Cancellation Test Attention and Executive Functions: Attentive matrice and Trail Making test For each listed test, equivalent score, from 0 to 4, is used.

    Mood Disorders. HADS test (score 0-21 : 0-7= Normal; 8-21 Mood disorders

    Measured: ARM 1: preop, 1-2 months postop, 3-4 months postop, 6-8 months postop, 12 months postop; ARM 2/3/4: before starting treatment, at 2-3 and 6-9 months during treatment, before surgery (if indicated), 1 month postop, 2-3 months postop

Timeline

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

  1. First posted24 Apr 2024
  2. Study start7 Mar 2024
  3. Primary completion28 Feb 2028 (estimated)
  4. Study completion28 Feb 2028 (estimated)

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 N/A
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
Patients immediately candidate for resection will be assessed neurologically, neuropsychologically and by functional MRI. Extent of resection will be assessed on \<48hrs and 2-month MRI. Neurological and neuropsychological assessment will be performed during regular follow-up. Patients not requiring an adjuvant treatment according to tumor board meeting will be submitted to functional MRI at 4-8 and 12 months from surgery. Patients not immediately eligible for resection will be submitted to biopsy for histomolecular definition. Patients not requiring radiation therapy will be submitted to neurological, neuropsychological, and functional MRI evaluation. Upon clinical context, patients will undergo motor rehabilitation and/or chemotherapy. After 3-6 months, patients will undergo functional MRI and evaluated for surgery. Neurological and neuropsychological evaluation will be performed at treatment initiation, every month during treatment, at admission for surgery and 1 month after surgery.
Masking
None (open label)
Enrolment
400 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06381726
Sponsor's protocol ID
Progetto AIRC IG-2022 ID 27184
Status last verified
Apr 2024
First submitted
28 Mar 2024
Last updated
24 Apr 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Bello L, Riva M, Fava E, Ferpozzi V, Castellano A, Raneri F, Pessina F, Bizzi A, Falini A, Cerri G. Tailoring neurophysiological strategies with clinical context enhances resection and safety and expands indications in gliomas involving motor pathways. Neuro Oncol. 2014 Aug;16(8):1110-28. doi: 10.1093/neuonc/not327. Epub 2014 Feb 4.

    PubMed 24500420

  • Castellano A, Donativi M, Ruda R, De Nunzio G, Riva M, Iadanza A, Bertero L, Rucco M, Bello L, Soffietti R, Falini A. Evaluation of low-grade glioma structural changes after chemotherapy using DTI-based histogram analysis and functional diffusion maps. Eur Radiol. 2016 May;26(5):1263-73. doi: 10.1007/s00330-015-3934-6. Epub 2015 Aug 30.

    PubMed 26318368

  • Cochereau J, Deverdun J, Herbet G, Charroud C, Boyer A, Moritz-Gasser S, Le Bars E, Molino F, Bonafe A, Menjot de Champfleur N, Duffau H. Comparison between resting state fMRI networks and responsive cortical stimulations in glioma patients. Hum Brain Mapp. 2016 Nov;37(11):3721-3732. doi: 10.1002/hbm.23270.

    PubMed 27246771

  • Fornia L, Ferpozzi V, Montagna M, Rossi M, Riva M, Pessina F, Martinelli Boneschi F, Borroni P, Lemon RN, Bello L, Cerri G. Functional Characterization of the Left Ventrolateral Premotor Cortex in Humans: A Direct Electrophysiological Approach. Cereb Cortex. 2018 Jan 1;28(1):167-183. doi: 10.1093/cercor/bhw365.

    PubMed 27920095

  • Fornia L, Rossi M, Rabuffetti M, Leonetti A, Puglisi G, Vigano L, Simone L, Howells H, Bellacicca A, Bello L, Cerri G. Direct Electrical Stimulation of Premotor Areas: Different Effects on Hand Muscle Activity during Object Manipulation. Cereb Cortex. 2020 Jan 10;30(1):391-405. doi: 10.1093/cercor/bhz139.

    PubMed 31504261

  • Fornia L, Rossi M, Rabuffetti M, Bellacicca A, Vigano L, Simone L, Howells H, Puglisi G, Leonetti A, Callipo V, Bello L, Cerri G. Motor impairment evoked by direct electrical stimulation of human parietal cortex during object manipulation. Neuroimage. 2022 Mar;248:118839. doi: 10.1016/j.neuroimage.2021.118839. Epub 2021 Dec 25.

    PubMed 34963652

  • Howells H, Puglisi G, Leonetti A, Vigano L, Fornia L, Simone L, Forkel SJ, Rossi M, Riva M, Cerri G, Bello L. The role of left fronto-parietal tracts in hand selection: Evidence from neurosurgery. Cortex. 2020 Jul;128:297-311. doi: 10.1016/j.cortex.2020.03.018. Epub 2020 Apr 10.

    PubMed 32362441

  • Kong NW, Gibb WR, Badhe S, Liu BP, Tate MC. Plasticity of the Primary Motor Cortex in Patients with Primary Brain Tumors. Neural Plast. 2020 Jul 3;2020:3648517. doi: 10.1155/2020/3648517. eCollection 2020.

    PubMed 32714384

  • Puglisi G, Howells H, Sciortino T, Leonetti A, Rossi M, Conti Nibali M, Gabriel Gay L, Fornia L, Bellacicca A, Vigano L, Simone L, Catani M, Cerri G, Bello L. Frontal pathways in cognitive control: direct evidence from intraoperative stimulation and diffusion tractography. Brain. 2019 Aug 1;142(8):2451-2465. doi: 10.1093/brain/awz178.

    PubMed 31347684

  • Raffin E, Siebner HR. Use-Dependent Plasticity in Human Primary Motor Hand Area: Synergistic Interplay Between Training and Immobilization. Cereb Cortex. 2019 Jan 1;29(1):356-371. doi: 10.1093/cercor/bhy226.

    PubMed 30364930

  • Rossi M, Fornia L, Puglisi G, Leonetti A, Zuccon G, Fava E, Milani D, Casarotti A, Riva M, Pessina F, Cerri G, Bello L. Assessment of the praxis circuit in glioma surgery to reduce the incidence of postoperative and long-term apraxia: a new intraoperative test. J Neurosurg. 2019 Jan 1;130(1):17-27. doi: 10.3171/2017.7.JNS17357. Epub 2018 Feb 23.

    PubMed 29473778

  • Rossi M, Ambrogi F, Gay L, Gallucci M, Conti Nibali M, Leonetti A, Puglisi G, Sciortino T, Howells H, Riva M, Pessina F, Navarria P, Franzese C, Simonelli M, Ruda R, Bello L. Is supratotal resection achievable in low-grade gliomas? Feasibility, putative factors, safety, and functional outcome. J Neurosurg. 2019 May 17;132(6):1692-1705. doi: 10.3171/2019.2.JNS183408. Print 2020 Jun 1.

    PubMed 31100730

  • Rossi M, Conti Nibali M, Vigano L, Puglisi G, Howells H, Gay L, Sciortino T, Leonetti A, Riva M, Fornia L, Cerri G, Bello L. Resection of tumors within the primary motor cortex using high-frequency stimulation: oncological and functional efficiency of this versatile approach based on clinical conditions. J Neurosurg. 2019 Aug 9;133(3):642-654. doi: 10.3171/2019.5.JNS19453. Print 2020 Sep 1.

    PubMed 31398706

  • Rossi M, Sciortino T, Conti Nibali M, Gay L, Vigano L, Puglisi G, Leonetti A, Howells H, Fornia L, Cerri G, Riva M, Bello L. Clinical Pearls and Methods for Intraoperative Motor Mapping. Neurosurgery. 2021 Feb 16;88(3):457-467. doi: 10.1093/neuros/nyaa359.

    PubMed 33476393

  • Rossi M, Gay L, Ambrogi F, Conti Nibali M, Sciortino T, Puglisi G, Leonetti A, Mocellini C, Caroli M, Cordera S, Simonelli M, Pessina F, Navarria P, Pace A, Soffietti R, Ruda R, Riva M, Bello L. Association of supratotal resection with progression-free survival, malignant transformation, and overall survival in lower-grade gliomas. Neuro Oncol. 2021 May 5;23(5):812-826. doi: 10.1093/neuonc/noaa225.

    PubMed 33049063

Questions about this trial

What is this clinical trial studying?

A study testing Resting State Functional Magnetic Resonance Imaging (rs-fMRI), Up-front Motor Rehabilitation and Up-front Chemotherapy in people with Glioma and Glioma, Malignant, run by University of Milan at 1 site in Italy.

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 8 inclusion and 3 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: looking for participants now, as of the sponsor's last update on 24 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. 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.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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

Contact Lorenzo Bello, MD (0039-340-217-1453, lorenzo.bello@unimi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Muscle power (time frame: ARM 1: preop, 1-2 months postop, 3-4 months postop, 6-8 months postop, 12 months postop; ARM 2/3/4: before starting treatment, at 2-3 and 6-9 months during treatment, before surgery (if indicated), 1 month postop, 2-3 months postop). The study lists 2 primary outcomes in all. 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 NCT06381726, which also lists 27 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 24 Apr 2024.

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