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

Study Purpose

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. 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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria (ARM 1):

- 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.

Inclusion Criteria (ARM 2/3/4):

- 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.

Exclusion Criteria:

- Age <18 years.

- Inability to adhere to standard study controls.

- Subjects unable to understand and freely provide consent to the study

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT06381726
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	N/A
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	University of Milan
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Lorenzo Bello, MD
Principal Investigator Affiliation	University of Milan
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	Italy
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Glioma, Glioma, Malignant

Arms & Interventions

Arms

Active Comparator: Spontaneous motor reorganization: observation

Only neurological and neuropsychological assessment as per normal clinical routine and conventional and advanced functional, resting-state MRI acquisitions

Experimental: Enhanced motor reorganization: upfront Motor Rehabilitation

Patients 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).

Experimental: Enhanced motor reorganization: upfront Chemotherapy

Temozolomide-based regimen of 6 months duration is applied. Treatment will be discontinued in case of toxicity (G2-G4).

Experimental: Enhanced motor reorganization: upfront Chemotherapy + Motor Rehabilitation

Temozolomide-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).

Interventions

Diagnostic Test: - Resting State Functional Magnetic Resonance Imaging (rs-fMRI)

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

Behavioral: - Up-front Motor Rehabilitation

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

Drug: - Up-front Chemotherapy

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

Contact a Trial Team

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International Sites

IRCCS Ospedale Galeazzi Sant'Ambrogio, Milan, Lombardy, Italy

Status

Recruiting

Address

IRCCS Ospedale Galeazzi Sant'Ambrogio

Milan, Lombardy, 20157

Site Contact

Lorenzo Bello, MD

[email protected]

0039-340-217-1453

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