GlioblastomaPhase 1GLINERANCT06418113
Neoadjuvant Radio-chemotherapy Safety Pilot Study in Patients With Glioblastoma
A Phase 1 study testing hypofractionated stereotactic radiotherapy, Stereotactic biopsy and resection in people with Glioblastoma and Glioblastoma Multiforme, run by Hospital San Carlos, Madrid at 1 site in Spain.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Glioblastoma, Glioblastoma Multiforme, Glioblastoma, IDH-wildtype
- What is being tested?
- hypofractionated stereotactic radiotherapy, Stereotactic biopsy and resection
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteSpain
- Study dates
- 21 Mar 2024to 21 Mar 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age between 18 and 75 years.
- Unifocal disease.
- Unilobar tumor.
- Clinical-radiological diagnosis of supratentorial unicentric high-grade glioma, eligible for macroscopically complete resection.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Spain1 site, 1 recruiting
- Recruiting
Hospital Clínico San Carlos
Madrid, 28040
Juan Antonio Barcia, +34 913303506, jabarcia@ucm.es
Mª Rebeca Lliguin León, 622059861, rebeca.lliguin.leon@gmail.com
About this study
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?
Read more
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.
Read the 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
- Glioblastoma, Glioblastoma Multiforme, Glioblastoma, IDH-wildtype, Radiotherapy; Complications, Cancer Brain
- Being tested
- hypofractionated stereotactic radiotherapy, Stereotactic biopsy, resection, Chemotherapy, radiotherapy Stupp protocol
- Medical subject headings
- Glioblastoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
hypofractionated stereotactic radiotherapyRadiation
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 biopsyProcedure or surgery
Stereotactic biopsy
resectionProcedure or surgery
supramarginal resection guided by 5-ALA under intraoperative neurophysiological monitoring
ChemotherapyDrug
4 weeks post-surgery, temozolomide (TMZ) will be administered for 6 months
radiotherapy Stupp protocolRadiation
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 ProtocolDrug
temozolomide (TMZ) will be administered for 6 months according to the Stupp protocol.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Procedure: resection; Radiation: radiotherapy Stupp protocol; Drug: Chemotherapy Stupp Protocol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Emergent Adverse Events assessed by physical and neurological examination
Information on adverse events will be reviewed through direct questioning of the patient.
Measured: 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.
Measured: Clinical follow-up every month for 2 years
Emergent Adverse Events assessed by brain RM image
brain RM image, for neuroradiological follow-up
Measured: 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
Measured: every 6 months after surgery, for 2 years
Secondary outcomes (4)
Efficacy assessed by progression-free survival (PFS)
Progression-free survival (PFS), a measure of how long a patient receives treatment before the cancer begins to grow.
Measured: through study completion, an average of 2 yeas.
Efficacy assessed by overall survival (OS)
Overall survival (OS), how long patients live after starting treatment.
Measured: through study completion, an average of 2 yeas.
Quality of life assessed by The Functional Assessment of Cancer Therapy-Brain (FACT-Br)
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
Measured: every 3 months after surgery, for 2 years
Cognitive functionality assessed by MONTREAL COGNITIVE ASSESSMENT (MOCA)
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
Measured: every 3 months after surgery, for 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2024
- Study start21 Mar 2024
- Primary completion21 Nov 2026 (estimated)
- Study completion21 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital San Carlos, Madrid
- Sponsor type
- University, hospital or other
- Collaborators
- Asociación de Afectados Por Tumores Cerebrales en España (ASATE)
- Responsible party
- Principal investigator, Juan Antonio Barcia Albacar, Hospital San Carlos, Madrid
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06418113
- Sponsor's protocol ID
- 22/399
- Acronym
- GLINERA
- Status last verified
- May 2024
- First submitted
- 3 Apr 2024
- Last updated
- 16 May 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant Radio-chemotherapy Safety Pilot Study in Patients With Glioblastoma
- ClinicalTrials.gov ID
- NCT06418113
- Acronym / sponsor ID
- GLINERA / 22/399
- Conditions
- Glioblastoma, Glioblastoma Multiforme, Glioblastoma, IDH-wildtype, Radiotherapy; Complications, Cancer Brain
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Hospital San Carlos, MadridUniversity, hospital or other
- Collaborators
- Asociación de Afectados Por Tumores Cerebrales en España (ASATE)
- Study start
- 21 Mar 2024 (actual)
- Primary completion
- 21 Nov 2026 (estimated)
- Study completion
- 21 Mar 2027 (estimated)
- First posted
- 16 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Radiation: hypofractionated stereotactic radiotherapy, Procedure: Stereotactic biopsy, Procedure: resection, Drug: ChemotherapyStereotactic 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. |
| Stupp Protocol | Other | Procedure: resection, Radiation: radiotherapy Stupp protocol, Drug: Chemotherapy Stupp ProtocolThe Stupp protocol is a standard treatment regimen for glioblastoma, which involves a combination of radiotherapy and chemotherapy. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age between 18 and 75 years.
- Unifocal disease.
- Unilobar tumor.
- Clinical-radiological diagnosis of supratentorial unicentric high-grade glioma, eligible for macroscopically complete resection.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| hypofractionated stereotactic radiotherapyconformal 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 | Radiation | Experimental |
| Stereotactic biopsyStereotactic biopsy | Procedure or surgery | Experimental |
| resectionsupramarginal resection guided by 5-ALA under intraoperative neurophysiological monitoring | Procedure or surgery | Experimental, Stupp Protocol |
| Chemotherapy4 weeks post-surgery, temozolomide (TMZ) will be administered for 6 months | Drug | Experimental |
| radiotherapy Stupp protocolradiotherapy + 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. | Radiation | Stupp Protocol |
| Chemotherapy Stupp Protocoltemozolomide (TMZ) will be administered for 6 months according to the Stupp protocol. | Drug | Stupp Protocol |
Primary outcome
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.
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.
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
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
4 secondary outcomes
Efficacy assessed by progression-free survival (PFS)
Time frame: through study completion, an average of 2 yeas.
Efficacy assessed by overall survival (OS)
Time frame: through study completion, an average of 2 yeas.
Quality of life assessed by The Functional Assessment of Cancer Therapy-Brain (FACT-Br)
Time frame: every 3 months after surgery, for 2 years
Cognitive functionality assessed by MONTREAL COGNITIVE ASSESSMENT (MOCA)
Time frame: every 3 months after surgery, for 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing hypofractionated stereotactic radiotherapy, Stereotactic biopsy and resection in people with Glioblastoma and Glioblastoma Multiforme, run by Hospital San Carlos, Madrid at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Juan Antonio Barcia (+34 913303506, jabarcia@ucm.es), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Emergent Adverse Events assessed by physical and neurological examination (time frame: Clinical follow-up every month for 2 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2024.