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NCT Number: NCT06418113

Neoadjuvant Radio-chemotherapy Safety Pilot Study in Patients With Glioblastoma

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.

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Key information

Conditions

Glioblastoma Astrocytoma Brain Diseases Brain Neoplasms Cancer Brain Central Nervous System Diseases Central Nervous System Neoplasms Glioblastoma Multiforme Glioblastoma, IDH-wildtype Glioma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms, Neuroepithelial Nervous System Diseases Nervous System Neoplasms Neuroectodermal Tumors Radiotherapy; Complications

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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

Stereotactic biopsy

Procedure

Stereotactic biopsy

Resection

Procedure

supramarginal resection guided by 5-ALA under intraoperative neurophysiological monitoring

Chemotherapy

Drug

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

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.

Chemotherapy Stupp Protocol

Drug

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

Primary outcomes

  1. Emergent Adverse Events assessed by physical and neurological examination

    Time frame: Clinical follow-up every month for 2 years

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

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

    Time frame: 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.

  3. Emergent Adverse Events assessed by brain RM image

    Time frame: every 3 months after surgery, for 2 years

    brain RM image, for neuroradiological follow-up

  4. Emergent Adverse Events assessed by AC_PET with 18-FdG

    Time frame: every 6 months after surgery, for 2 years

    AC_PET image, for neuroradiological follow-up

Secondary outcomes

  1. Efficacy assessed by progression-free survival (PFS)

    Time frame: 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.

  2. Efficacy assessed by overall survival (OS)

    Time frame: through study completion, an average of 2 yeas.

    Overall survival (OS), how long patients live after starting treatment.

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

    Time frame: 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

  4. Cognitive functionality assessed by MONTREAL COGNITIVE ASSESSMENT (MOCA)

    Time frame: 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

Study contacts

Contact information is provided by the study sponsor or research team.

Juan Antonio Barcia

CONTACT

[email protected]

+34 913303506

Mª Rebeca Lliguin León

CONTACT

[email protected]

+34 622059861

Sponsors and collaborators

Lead sponsor

Hospital San Carlos, Madrid

Other

Collaborators

  • Asociación de Afectados Por Tumores Cerebrales en España (ASATE)

Registry information

Acronym: GLINERA

Important dates

Study start
2024
Primary completion
2026
Study completion
2027
First posted
May 16, 2024
Registry last updated
May 16, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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