Neoadjuvant Radio-chemotherapy Safety Pilot Study in Patients With Glioblastoma

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Neoadjuvant Radio-chemotherapy Safety Pilot Study in Patients With Glioblastoma

Study Purpose

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.

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 - 75 Years
Gender	All

More Inclusion & Exclusion Criteria

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.

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.	NCT06418113
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.	Phase 1
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Hospital San Carlos, Madrid
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	N/A
Principal Investigator Affiliation	N/A
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	Spain
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Glioblastoma, Glioblastoma Multiforme, Glioblastoma, IDH-wildtype, Radiotherapy; Complications, Cancer Brain

Additional Details

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.

Arms & Interventions

Arms

Experimental: Experimental

Stereotactic biopsy will be performed on patients in the experimental group, who will then be discharged. If the histopathological diagnosis is not wildtype IDH non-mutated glioblastoma, the patient will be withdrawn from the study and receive conventional treatment. If wildtype IDH non-mutated glioblastoma is diagnosed, ten days after the biopsy, 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, 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 (GEINO, 2016). Five weeks later, patients will undergo supramarginal resection guided by 5-ALA under intraoperative neurophysiological monitoring. Starting from 4 weeks post-surgery, TMZ will be administered for 6 months according to the Stupp protocol.

Other: Stupp Protocol

The Stupp protocol is a standard treatment regimen for glioblastoma, which involves a combination of radiotherapy and chemotherapy.

Interventions

Radiation: - hypofractionated stereotactic radiotherapy

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

Procedure: - Stereotactic biopsy

Stereotactic biopsy

Procedure: - resection

supramarginal resection guided by 5-ALA under intraoperative neurophysiological monitoring

Drug: - Chemotherapy

4 weeks post-surgery, temozolomide (TMZ) will be administered for 6 months

Radiation: - radiotherapy 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.

Drug: - Chemotherapy Stupp Protocol

temozolomide (TMZ) will be administered for 6 months according to the Stupp protocol.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.