Clinical trial NCT06418113: Neoadjuvant Radio-chemotherapy Safety Pilot Study in Patients With Glioblastoma
Official title: Neoadjuvant Radio-chemotherapy Safety Pilot Study in Patients With Glioblastoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Glioblastoma
Glioblastoma Multiforme
Glioblastoma, IDH-wildtype
Radiotherapy; Complications
Cancer Brain
Lead sponsor: Hospital San Carlos, Madrid
Sponsor class: OTHER
Collaborators: name: Asociación de Afectados Por Tumores Cerebrales en España (ASATE)
First posted: 2024-05-16
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Emergent Adverse Events assessed by physical and neurological examination
timeFrame: Clinical follow-up every month for 2 years
measure: Emergent Adverse Events assessed by evaluation of the results of the analysis with hematology and biochemistry.
timeFrame: Clinical follow-up every month for 2 years
measure: Emergent Adverse Events assessed by brain RM image
timeFrame: every 3 months after surgery, for 2 years
measure: Emergent Adverse Events assessed by AC_PET with 18-FdG
timeFrame: every 6 months after surgery, for 2 years
Secondary outcomes:
measure: Efficacy assessed by progression-free survival (PFS)
timeFrame: through study completion, an average of 2 yeas.
measure: Efficacy assessed by overall survival (OS)
timeFrame: through study completion, an average of 2 yeas.
measure: Quality of life assessed by The Functional Assessment of Cancer Therapy-Brain (FACT-Br)
timeFrame: every 3 months after surgery, for 2 years
measure: Cognitive functionality assessed by MONTREAL COGNITIVE ASSESSMENT (MOCA)
timeFrame: every 3 months after surgery, for 2 years
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
Study officials:
References: