Glioblastoma, Glioblastoma Multiforme, Glioblastoma, IDH-wildtype, Radiotherapy; Complications, Cancer Brain
Conditions
Brief summary
The goal of this clinical trial is to evaluate the safety and efficacy of neoadjuvant radiochemotherapy in the surgical resection of glioblastoma (GBM). The main questions it aims to answer are: * What is the safety profile of neoadjuvant radiochemotherapy in terms of neurological deficit, radionecrosis, edema, headache, wound dehiscence, infection, and cerebrospinal fluid fistula? * What is the efficacy of neoadjuvant radiochemotherapy in terms of progression-free survival, overall survival, cognitive function, and quality of life? Participants will undergo the following tasks and treatments: * Stereotactic biopsy and diagnosis confirmation. * Conformal hypofractionated stereotactic radiotherapy with concurrent temozolomide. * Supramarginal resection guided by 5-ALA under intraoperative neurophysiological monitoring. * Maintenance temozolomide administration for 6 months. Researchers will compare the group receiving neoadjuvant radiochemotherapy to the control group following the standard Stupp protocol to assess safety and efficacy outcomes.
Detailed description
Objectives: To study the safety (primary) and efficacy (secondary) of neoadjuvant radiochemotherapy in the surgical resection of glioblastoma (GBM). Safety measures include: neurological deficit, radionecrosis (radiological and clinical), edema, headache, wound dehiscence, infection, and cerebrospinal fluid fistula. Efficacy measures include progression-free survival (PFS), overall survival (OS), cognitive function (MoCA Scale), and quality of life (EuroQol scales, EORTC QLQ-HN35, FACT-Br, and TWiST). Methods: Pilot safety and efficacy study in 6 patients compared to 6 controls. 2-year follow-up. A data safety monitoring committee will review the data one month after surgery for each of the first three patients to decide whether to stop or continue the study. Stereotactic biopsy will be performed, and if GBM is diagnosed, patients will undergo conformal hypofractionated stereotactic radiotherapy to the FLAIR hyperintense signal including the contrast-enhancing tumor on T1, with a total dose of 3990 cGy at the margin in 15 fractions of 266 cGy and concurrent temozolomide (TMZ). 5 weeks later, patients will undergo supramarginal resection guided by 5-ALA under intraoperative neurophysiological monitoring. 7 days after surgery, maintenance TMZ will be administered for 6 months. The control group will follow standard treatment (Stupp protocol). Data analysis will be performed using non-parametric tests. Samples from successive surgeries will be studied with histology, molecular biology, and cell cultures.
Interventions
conformal hypofractionated stereotactic radiotherapy to the FLAIR hyperintense signal, including the contrast-enhancing tumor on T1, with a total dose of 3990 cGy at the margin in 15 fractions of 266 cGy, one session per day, five days a week, and concurrent temozolomide (TMZ) at 75 mg/m2/day for 7 days/week during the irradiation period
PROCEDUREStereotactic biopsy
Stereotactic biopsy
PROCEDUREresection
supramarginal resection guided by 5-ALA under intraoperative neurophysiological monitoring
DRUGChemotherapy
4 weeks post-surgery, temozolomide (TMZ) will be administered for 6 months
RADIATIONradiotherapy Stupp protocol
radiotherapy + TMZ concurrently after 4 weeks of resection surgery, as per usual protocol: Three-dimensional radiotherapy planning to deliver a total dose of 60 Gy, with a fractionation of 2 Gy/day, 5 days/week, encompassing a 1-2 cm margin around the contrast-enhancing region defined on T1 imaging or the entire abnormal volume defined on T2 or FLAIR imaging (Li et al., 2016) + TMZ at 75 mg/m2/day for 7 days/week, for 6 weeks during radiotherapy.
DRUGChemotherapy Stupp Protocol
temozolomide (TMZ) will be administered for 6 months according to the Stupp protocol.
Sponsors
Asociación de Afectados Por Tumores Cerebrales en España (ASATE)
Hospital San Carlos, Madrid
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age between 18 and 75 years. * Unifocal disease. * Unilobar tumor. * Clinical-radiological diagnosis of supratentorial unicentric high-grade glioma, eligible for macroscopically complete resection.
Exclusion criteria
* Multilobar tumor, interhemispheric or infratentorial extension, or multifocal disease. * Midline shift greater than 1 cm. * Intracranial hypertension symptoms requiring corticosteroid treatment. * Synchronous neoplasia. * Any contraindication for surgery, radiotherapy, or TMZ treatment. * Cognitive impairment. * Rejection of informed consent. * Inability to follow up for 2 years. * Women of childbearing potential according to the Clinical Trial Facilitation Group (CTFG) criteria. (https://www.hma.eu/fileadmin/dateien/Human\_Medicines/01-About\_HMA/Working\_Groups/CTFG/2020\_09\_HMA\_CTFG\_Contraception\_guidance\_Version\_1.1.pdf) * Hypersensitivity to the active ingredient or any excipients of the investigational drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Emergent Adverse Events assessed by AC_PET with 18-FdG | every 6 months after surgery, for 2 years | AC\_PET image, for neuroradiological follow-up |
| Emergent Adverse Events assessed by physical and neurological examination | Clinical follow-up every month for 2 years | Information on adverse events will be reviewed through direct questioning of the patient. |
| Emergent Adverse Events assessed by evaluation of the results of the analysis with hematology and biochemistry. | Clinical follow-up every month for 2 years | Information on adverse events will be reviewed through the results of examinations, complementary tests and analytical parameters. |
| Emergent Adverse Events assessed by brain RM image | every 3 months after surgery, for 2 years | brain RM image, for neuroradiological follow-up |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy assessed by progression-free survival (PFS) | through study completion, an average of 2 yeas. | Progression-free survival (PFS), a measure of how long a patient receives treatment before the cancer begins to grow. |
| Efficacy assessed by overall survival (OS) | through study completion, an average of 2 yeas. | Overall survival (OS), how long patients live after starting treatment. |
| Quality of life assessed by The Functional Assessment of Cancer Therapy-Brain (FACT-Br) | every 3 months after surgery, for 2 years | A commonly used instrument measuring general quality of life (QOL) that reflects symptoms or problems associated with brain malignancies across 5 scales. Patients rate all 5 items using a five-point Likert scale ranging from 0 not at all to 4 very much. Overall, higher ratings suggest higher QOL |
| Cognitive functionality assessed by MONTREAL COGNITIVE ASSESSMENT (MOCA) | every 3 months after surgery, for 2 years | It has been shown to be useful at detecting cognitive dysfunction in brain metastases. The test is a one-page, 30-point test that can be administered in 10 minutes. It assesses short-term memory recall (5 points), visuospatial abilities through clock-drawing (3 points) and cube copy (1 point), and orientation (6 points). Executive function is assessed through modified Trail Making Part B (1 point), phonemic fluency (1 point), and verbal abstraction (2 points). A sustained-attention task (1 point), digit span (2 points), and serial calculation (3 points) test attention, concentration, and working memory. And lastly, language is assessed through naming low-familiarity animals (3 points), sentence repetition (2 points), and the fluency task |
Countries
Spain
Contacts
Primary ContactJuan Antonio Barcia
Backup ContactMª Rebeca Lliguin León
Outcome results
None listed