## Protocol Section
### Identification Module
**NCT ID:** NCT06418113

**Acronym:** GLINERA

**Brief Title:** Neoadjuvant Radio-chemotherapy Safety Pilot Study in Patients With Glioblastoma

**Official Title:** Neoadjuvant Radio-chemotherapy Safety Pilot Study in Patients With Glioblastoma

#### Organization Study ID Info
**ID:** 22/399
#### Organization
**Class:** OTHER
**Full Name:** Hospital San Carlos, Madrid
### Status Module
#### Completion Date
**Date:** 2027-03-21

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-16

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-13

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2026-11-21

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-03-21

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-16
**Type:** ACTUAL
**Study First Submit Date:** 2024-04-03
**Study First Submit QC Date:** 2024-05-13
### Sponsor Collaborators Module

#### Collaborators

**Class:** UNKNOWN

**Name:** Asociación de Afectados Por Tumores Cerebrales en España (ASATE)

#### Lead Sponsor

**Class:** OTHER

**Name:** Hospital San Carlos, Madrid

#### Responsible Party

**Investigator Affiliation:** Hospital San Carlos, Madrid

**Investigator Full Name:** Juan Antonio Barcia Albacar

**Investigator Title:** Professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

### Description Module

**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.

### Conditions Module

**Conditions:**

- Glioblastoma

- Glioblastoma Multiforme

- Glioblastoma, IDH-wildtype

- Radiotherapy; Complications

- Cancer Brain

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 12

**Type:** ESTIMATED

**Phases:**

- PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 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.

**Intervention Names:**

- Radiation: hypofractionated stereotactic radiotherapy

- Procedure: Stereotactic biopsy

- Procedure: resection

- Drug: Chemotherapy

**Label:** Experimental

**Type:** EXPERIMENTAL

#### Arm Group 2

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

**Intervention Names:**

- Procedure: resection

- Radiation: radiotherapy Stupp protocol

- Drug: Chemotherapy Stupp Protocol

**Label:** Stupp Protocol

**Type:** OTHER

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Experimental

**Description:** 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

**Name:** hypofractionated stereotactic radiotherapy

**Type:** RADIATION

#### Intervention 2

**Arm Group Labels:**

- Experimental

**Description:** Stereotactic biopsy

**Name:** Stereotactic biopsy

**Type:** PROCEDURE

#### Intervention 3

**Arm Group Labels:**

- Experimental

- Stupp Protocol

**Description:** supramarginal resection guided by 5-ALA under intraoperative neurophysiological monitoring

**Name:** resection

**Type:** PROCEDURE

#### Intervention 4

**Arm Group Labels:**

- Experimental

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

**Name:** Chemotherapy

**Type:** DRUG

#### Intervention 5

**Arm Group Labels:**

- Stupp Protocol

**Description:** 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.

**Name:** radiotherapy Stupp protocol

**Type:** RADIATION

#### Intervention 6

**Arm Group Labels:**

- Stupp Protocol

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

**Name:** Chemotherapy Stupp Protocol

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

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

**Measure:** Emergent Adverse Events assessed by physical and neurological examination

**Time Frame:** Clinical follow-up every month for 2 years

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

**Measure:** 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

**Description:** brain RM image, for neuroradiological follow-up

**Measure:** Emergent Adverse Events assessed by brain RM image

**Time Frame:** every 3 months after surgery, for 2 years

**Description:** AC_PET image, for neuroradiological follow-up

**Measure:** Emergent Adverse Events assessed by AC_PET with 18-FdG

**Time Frame:** every 6 months after surgery, for 2 years

#### Secondary Outcomes

**Description:** Progression-free survival (PFS), a measure of how long a patient receives treatment before the cancer begins to grow.

**Measure:** Efficacy assessed by progression-free survival (PFS)

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

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

**Measure:** Efficacy assessed by overall survival (OS)

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

**Description:** 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

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

**Time Frame:** every 3 months after surgery, for 2 years

**Description:** 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

**Measure:** Cognitive functionality assessed by MONTREAL COGNITIVE ASSESSMENT (MOCA)

**Time Frame:** every 3 months after surgery, for 2 years

### Eligibility Module

**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.

**Maximum Age:** 75 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** jabarcia@ucm.es

**Name:** Juan Antonio Barcia

**Phone:** +34 913303506

**Role:** CONTACT

**Contact 2:**

**Email:** rebeca.lliguin.leon@gmail.com

**Name:** Mª Rebeca Lliguin León

**Phone:** +34 622059861

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Madrid

**Contacts:**

***Contact 1:***

- **Email:** jabarcia@ucm.es

- **Name:** Juan Antonio Barcia

- **Phone:** +34 913303506

- **Role:** CONTACT

***Contact 2:***

- **Email:** rebeca.lliguin.leon@gmail.com

- **Name:** Mª Rebeca Lliguin León

- **Phone:** 622059861

- **Role:** CONTACT

**Country:** Spain

**Facility:** Hospital Clínico San Carlos

**Status:** RECRUITING

**Zip:** 28040

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000001254

- Term: Astrocytoma

- ID: D000005910

- Term: Glioma

- ID: D000018302

- Term: Neoplasms, Neuroepithelial

- ID: D000017599

- Term: Neuroectodermal Tumors

- ID: D000009373

- Term: Neoplasms, Germ Cell and Embryonal

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000009375

- Term: Neoplasms, Glandular and Epithelial

- ID: D000009380

- Term: Neoplasms, Nerve Tissue

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: All

- Name: All Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M9019

- Name: Glioblastoma

- Relevance: HIGH

- As Found: Glioblastoma

- ID: M4561

- Name: Astrocytoma

- Relevance: LOW

- As Found: Unknown

- ID: M9020

- Name: Glioma

- Relevance: LOW

- As Found: Unknown

- ID: M20446

- Name: Neoplasms, Neuroepithelial

- Relevance: LOW

- As Found: Unknown

- ID: M19845

- Name: Neuroectodermal Tumors

- Relevance: LOW

- As Found: Unknown

- ID: M20388

- Name: Neuroectodermal Tumors, Primitive

- Relevance: LOW

- As Found: Unknown

- ID: M12318

- Name: Neoplasms, Germ Cell and Embryonal

- Relevance: LOW

- As Found: Unknown

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M12320

- Name: Neoplasms, Glandular and Epithelial

- Relevance: LOW

- As Found: Unknown

- ID: M12325

- Name: Neoplasms, Nerve Tissue

- Relevance: LOW

- As Found: Unknown

- ID: T2518

- Name: Glioblastoma

- Relevance: HIGH

- As Found: Glioblastoma

- ID: T2519

- Name: Glioma

- Relevance: LOW

- As Found: Unknown

- ID: T4092

- Name: Neuroepithelioma

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000005909

- Term: Glioblastoma

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Derm

- Name: Dermatologic Agents

### Intervention Browse Module - Browse Leaves

- ID: M1692

- Name: Temozolomide

- Relevance: LOW

- As Found: Unknown

- ID: M3960

- Name: Aminolevulinic Acid

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
