Neoadjuvant Radio-chemotherapy Safety Pilot Study in Patients With Glioblastoma

NCT06418113 | Recruiting Phase 1

• 1 other identifier: 22/399
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Glioblastoma; Glioblastoma Multiforme; Glioblastoma, IDH-wildtype; Radiotherapy; Complications; Cancer Brain

Outcome Measures

Primary Outcomes (4)

• Emergent Adverse Events assessed by physical and neurological examination

  Information on adverse events will be reviewed through direct questioning of the patient.

  Clinical follow-up every month for 2 years

• Emergent Adverse Events assessed by evaluation of the results of the analysis with hematology and biochemistry.

  Information on adverse events will be reviewed through the results of examinations, complementary tests and analytical parameters.

  Clinical follow-up every month for 2 years

• Emergent Adverse Events assessed by brain RM image

  brain RM image, for neuroradiological follow-up

  every 3 months after surgery, for 2 years

• Emergent Adverse Events assessed by AC_PET with 18-FdG

  AC\_PET image, for neuroradiological follow-up

  every 6 months after surgery, for 2 years

Secondary Outcomes (4)

• Efficacy assessed by progression-free survival (PFS)

  through study completion, an average of 2 yeas.

• Efficacy assessed by overall survival (OS)

  through study completion, an average of 2 yeas.

• Quality of life assessed by The Functional Assessment of Cancer Therapy-Brain (FACT-Br)

  every 3 months after surgery, for 2 years

• Cognitive functionality assessed by MONTREAL COGNITIVE ASSESSMENT (MOCA)

  every 3 months after surgery, for 2 years

Study Arms (2)

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.

Radiation: hypofractionated stereotactic radiotherapy; Procedure: Stereotactic biopsy; Procedure: resection; Drug: Chemotherapy

Stupp Protocol

OTHER

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

Procedure: resection; Radiation: radiotherapy Stupp protocol; Drug: Chemotherapy Stupp Protocol

Interventions

hypofractionated stereotactic radiotherapy RADIATION

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

Experimental

Stereotactic biopsy PROCEDURE

Stereotactic biopsy

Experimental

resection PROCEDURE

supramarginal resection guided by 5-ALA under intraoperative neurophysiological monitoring

Experimental; Stupp Protocol

Chemotherapy DRUG

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

Experimental

radiotherapy Stupp protocol RADIATION

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.

Stupp Protocol

Chemotherapy Stupp Protocol DRUG

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

Stupp Protocol

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 75 years.
• Unifocal disease.
• Unilobar tumor.
• Clinical-radiological diagnosis of supratentorial unicentric high-grade glioma, eligible for macroscopically complete resection.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hospital San Carlos, Madrid: lead
• Asociación de Afectados Por Tumores Cerebrales en España (ASATE): collaborator

Study Sites (1)

Hospital Clínico San Carlos

Madrid, 28040, Spain

RECRUITING

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms

Interventions

Drug Therapy

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Central Study Contacts

Juan Antonio Barcia

CONTACT

+34 913303506; jabarcia@ucm.es

Mª Rebeca Lliguin León

CONTACT

+34 622059861; rebeca.lliguin.leon@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 3, 2024
• First Posted: May 16, 2024
• Study Start: March 21, 2024
• Primary Completion (Estimated): November 21, 2026
• Study Completion (Estimated): March 21, 2027
• Last Updated: May 16, 2024

Record last verified: 2024-05

Locations

ES (1)