Neoadjuvant Radio-chemotherapy Safety Pilot Study in Patients With Glioblastoma

Обзор

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.

Подробное описание

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.

Вмешательства

• Лучевая терапия 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
• Процедура Stereotactic biopsy
  Stereotactic biopsy
• Процедура resection
  supramarginal resection guided by 5-ALA under intraoperative neurophysiological monitoring
• Препарат Chemotherapy
  4 weeks post-surgery, temozolomide (TMZ) will be administered for 6 months
• Лучевая терапия 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.
• Препарат Chemotherapy Stupp Protocol
  temozolomide (TMZ) will be administered for 6 months according to the Stupp protocol.

Первичные конечные точки

• Emergent Adverse Events assessed by physical and neurological examination [Срок оценки: Clinical follow-up every month for 2 years]
• Emergent Adverse Events assessed by evaluation of the results of the analysis with hematology and biochemistry. [Срок оценки: Clinical follow-up every month for 2 years]
• Emergent Adverse Events assessed by brain RM image [Срок оценки: every 3 months after surgery, for 2 years]
• Emergent Adverse Events assessed by AC_PET with 18-FdG [Срок оценки: every 6 months after surgery, for 2 years]

Вторичные конечные точки (4)

• Efficacy assessed by progression-free survival (PFS) [Срок оценки: through study completion, an average of 2 yeas.]
• Efficacy assessed by overall survival (OS) [Срок оценки: through study completion, an average of 2 yeas.]
• Quality of life assessed by The Functional Assessment of Cancer Therapy-Brain (FACT-Br) [Срок оценки: every 3 months after surgery, for 2 years]
• Cognitive functionality assessed by MONTREAL COGNITIVE ASSESSMENT (MOCA) [Срок оценки: every 3 months after surgery, for 2 years]

Критерии участия

Критерии включения

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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Испания · 1 центр

• Hospital Clínico San Carlos — Madrid

Идентификаторы

NCT: NCT06418113 · 22/399

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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