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

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

NCT ID: NCT06381726

Condition: Glioma
Glioma, Malignant

Conditions: Official terms:
Glioma

Conditions: 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

Study type: Interventional

Study phase: N/A

Overall status: Recruiting

Study design:

Allocation: Non-Randomized

Intervention model: Parallel Assignment

Intervention 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.

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Diagnostic Test
Intervention name: Resting State Functional Magnetic Resonance Imaging (rs-fMRI)
Description: 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
Arm group label: Spontaneous motor reorganization: observation

Intervention type: Behavioral
Intervention name: Up-front Motor Rehabilitation
Description: 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
Arm group label: Enhanced motor reorganization: upfront Chemotherapy + Motor Rehabilitation
Arm group label: Enhanced motor reorganization: upfront Motor Rehabilitation

Intervention type: Drug
Intervention name: Up-front Chemotherapy
Description: 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
Arm group label: Enhanced motor reorganization: upfront Chemotherapy
Arm group label: Enhanced motor reorganization: upfront Chemotherapy + Motor Rehabilitation

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 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.

Criteria for eligibility:
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

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: IRCCS Ospedale Galeazzi Sant'Ambrogio

Address:
City: Milan
Zip: 20157
Country: Italy

Status: Recruiting

Contact:
Last name: Lorenzo Bello, MD

Phone: 0039-340-217-1453
Email: lorenzo.bello@unimi.it

Start date: March 7, 2024

Completion date: February 28, 2028

Lead sponsor:
Agency: University of Milan
Agency class: Other

Collaborator:
Agency: University of Turin, Italy
Agency class: Other

Source: University of Milan

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06381726