GlioblastomaNCT06551909
Radioimmunotherapy in Solid Tumors (PNRR-MCNT2-2023-12378239-Aim2)
A study testing Neoaddjuvant Stereotactic Radiotherapy with Simultaneous Integrated Boost in people with Glioblastoma, run by IRCCS San Raffaele at 1 site in Italy.
Trial summary
This is a prospective multicenter study of hypofractionated radiotherapy for the radiation treatment (RT) of solid tumors and in particular for Glioblastoma (in Aim 2). It is based on the results of ongoing studies at our Institute to validate the efficacy of extremely hypofractionated RT in neoadjuvant settings… Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Glioblastoma
- What is being tested?
- Neoaddjuvant Stereotactic Radiotherapy with Simultaneous Integrated Boost
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteItaly
- Study dates
- 31 Aug 2024to 28 Feb 2027
- Phase
- Interventional
- 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 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Diagnosis of Glioblastoma.
- ECOG performance score 0-2 (defined during the first visit)
- Surgically removable lesion (according to the operability criteria established by the Neurosurgery Unit)
- For healthy volunteers, people who are as comparable as possible with the patient population in terms of sex and age will be recruited
Who cannot join
- Previous stroke
- Presence of another primary and/or metastatic tumor For healthy volunteers also, absence of primary and/or metastatic tumor
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
IRCCS San Raffaele Scientific Institute
Milan, MI, 20132
Andrei Fodor, M.D., +390226437634, fodor.andrei@hsr.it
Di Muzio Nadia, Prof., +390226437643, dimuzio.nadia@hsr.it
About this study
Official title: Radioimmunotherapy in Solid Tumors (Aim 2- Stereotactic Neoadjuvant Radiotherapy for Glioblastoma)
This is a prospective multicenter study of hypofractionated radiotherapy for the radiation treatment (RT) of solid tumors and in particular for Glioblastoma (in Aim 2). It is based on the results of ongoing studies at our Institute to validate the efficacy of extremely hypofractionated RT in neoadjuvant settings, which observed immunostimulatory effects of RT and the synergy with immune components. The collaboration between San Raffaele Hospital (Milan), the IRCCS Istituto Nazionale dei Tumori Fondazione G. Pascale (Naples) and the San Giuseppe Moscati Hospital of National Relief and High Specialty (Avellino) will ensure that patient recruitment, treatment and monitoring can be translated into facilities of the National Health System using common procedures. The various departments involved will treat patients with the same methods synergistically exploring the immuno/biological factors related to efficacy (and/or toxicity), based on new radioimmunotherapeutic approaches. Clinical and research activity will be developed jointly, drawing on the expertise in radiotherapy, radiomics, oncology, imaging and immunotherapy skills already available.
Read the detailed description
This is a prospective multicenter pilot study. Functional and spectroscopic neuroradiological imaging will be adopted for treatment planning. Specialized software will be used to perform radiomic feature extraction and analysis of pre-trained neural networks from the advanced MRI (magnetic resonance imaging) and CT (computed tomography) used for simulation, to identify distribution patterns of aggressive and radioresistant disease areas, with higher probability of disease recurrence, and to intensify the dose on the areas identified as more aggressive, in order to counteract intrinsic radioresistance. The hypofractionated radiotherapy paradigm claims the benefit of reduced treatment times, improved quality of life, better access to specialized treatment centers and potentially improved tumor outcomes with greater disease control and less tumor repopulation. The rationale for neoadjuvant RT is based on the idea of counteracting the tumor's aggressive mechanisms with radiotherapy before the disease is surgically removed, in order to maximize the immunostimulatory potential of RT, and therefore reduce recurrences. Neoadjuvant treatment offers numerous advantages, first of all the ability to adjust the dose to the pathological volume identified by MRI and limit the volume of irradiated healthy brain tissue. Furthermore, the use of imaging derived from functional neuroradiological and spectroscopic techniques for treatment planning would allow us to increase the dose on the areas identified as more aggressive, in order act against intrinsic radioresistance. One of the major risks could be the possibility of developing radionecrosis, but this would not be a cause for concern in the neoadjuvant setting, as all irradiated tissue will then be surgically removed. Patients who agree to participate in the study and who would be candidates for radical surgical treatment, according to the evaluation of the Neurosurgery Department of our Institute, will be treated. These patients will receive neoadjuvant radiation treatment in 5 fractions delivering 30 Gy on PTV and 35-50 Gy on GTV, with a dose-escalation modality that involves increasing the dose to 35-40-42.5-45-47.5-50 Gy in groups of 5 consecutive patients, using standard chemotherapy (TMZ) after surgery.
Current diagnostic brain MRI allows a good definition of the initial disease and its most aggressive areas. Since relapses have always been found to occur in irradiated areas and recent studies have shown that reducing margins does not affect overall survival, smaller margins will be used from GTV to CTV and from CTV to PTV. Therefore, smaller volumes will be generated and treated with hypofractionation. Biological equivalent doses (BED) to the standard prescription will be delivered, with boost to a higher biological equivalent dose, in the most aggressive areas, in order to obtain better local control, maintaining an acceptable level of toxicity and therefore improve the evolution of the disease. CE marked devices (software) will be used according to the approved use, for the definition of the target (CT and MRI) and for the delivery of the treatment (linear accelerators) and the standard drug, which has the authorization for marketing, will be prescribed. Radiomic features related to local response and survival will be identified, to obtain a predictive model. At the same time, we will collect PMBC and patient serum in the biobank to identify presumed immunocorrelated of therapy efficacy and/or predictive biomarkers of response/toxicity to therapy. For comparative purposes, serum from healthy volunteers will also be collected, in numbers equivalent to patients and with sex and age characteristics comparable to the latter.
- Conditions
- Glioblastoma
- Being tested
- Neoaddjuvant Stereotactic Radiotherapy with Simultaneous Integrated Boost
- Keywords
- Glioblastoma, Neodjuvant Radiotherapy, Ultrahypofractionated Radiotherapy, Stereotactic Radiotherapy (SRT), Simultaneous Integrated Boost (SIB), Image Guidance
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neoaddjuvant Stereotactic Radiotherapy with Simultaneous Integrated BoostRadiation
Also called Ultrahypofractionated Radiotherapy
Patients with Glioblastoma will receive neoadjuvant stereotactic radiotherapy to Planning Target Volume (PTV) to 30 Gy in 5 fractions, and a Simultaneous Integrated Boost delivering 35-50 GY to GTV. Patients will be divided into groups of 5 and will receive (in the absence of 2 G4 toxicities per group), the following dose levels: 35-40-42.5-45-47.5 and 50 Gy. Standard Temozolomide chemotherapy will be prescribed after surgery.
| Study group | Role | What they receive |
|---|---|---|
| Treatment arm | Experimental | The 30 patients will receive neoadjuvant stereotactic radiotherapy in 5 fractions delivering 30 GY to PTV and 35-50 GY with Simultaneous Integrated Boost (SIB) to GTV using standard chemotherapy (TMZ) after surgery. GTV will be treated with escalating dose levels from 35 to 50 Gy. Patients will be divided into groups of 5 and will receive in the absence of 2 G4 toxicities per group, the following dose levels: 35-40-42.5-45-47.5 and 50 Gy Receives: Radiation: Neoaddjuvant Stereotactic Radiotherapy with Simultaneous Integrated Boost |
What is being measured
The primary outcome is the main question the study is designed to answer.
Acute toxicity
Incidence of acute toxicity of grade 3 or 4 as maximum toxicity value during the radiation treatment or in any case within a month of the end of SBRT, using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 scale (toxicity from 0- patients without toxicity to 5-death from toxicity)
Measured: one month
Secondary outcomes (12)
Disease Free Survival
Absence of disease progression during the follow-up
Measured: From the date of radiotherapy end until the date of first documented clinical progression or date of death from any cause, whichever came first, assessed up to 36 months]
Cancer Specific Survival
Death from disease progression during the follow-up
Measured: From the date of radiotherapy end until the date of first documented clinical progression or date of death from any cause, whichever came first, assessed up to 36 months]
Overall survival
Survival from all causes
Measured: From the date of radiotherapy end until the date of death from any cause, assessed up to 36 months
Local Relapse Free Survival
Local control of the disease (at the treated site)
Measured: From the date of radiotherapy end until the date of local progression or date of death from any cause, whichever came first, assessed up to 36 months
Intracranial Relapse Free Survival
Intracranial control of the disease (glioblastoma recurrence outside the treatment field)
Measured: From the date of radiotherapy end until the date of local progression or date of death from any cause, whichever came first, assessed up to 36 months
Extracranial Relapse Free Survival
Distant metastases
Measured: From the date of radiotherapy end until the date of local progression or date of death from any cause, whichever came first, assessed up to 36 months
Late toxicity
Toxicity developed after three months until the end of follow-up or death, assessed with Common Terminology Criteria for Adverse Events (CTCAE) v5.0 scale, assessed with Common Terminology Criteria for Adverse Events (CTCAE) v5.0 scale, which displayes grades from 1 to 5, with grade 1 meaning mild toxicity and grade 5 death related to toxicity
Measured: From three months after the start of radiotherapy until the end of follow-up or death, assessed up to 36 months
Subacute Toxicity
Incidence of acute toxicity of grade 3 or 4 as maximum toxicity value registered from one to three months of the end of SBRT, using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 scale (toxicity from 0- patients without toxicity to 5-death from toxicity)
Measured: From one up to three months after the start of radiotherapy
Incidence of Treatment-Emergent Adverse Events as assessed with brain tumor specific quality of life questionnaires
Survey with the questionnaire of European Organisation for Research and Treatment of Cancer (EORTC) Quality of life of brain tumor patients (EORTC QLQ BN20) which contains 25 questions on patients' quality of life with answers from 1, lowest grade, to 4, highest grade
Measured: 36 months
Incidence of Treatment-Emergent Adverse Events as assessed with functional-social- emotional and general well being questionnaires
Survey with the questionnaire FACT-Br on patients' quality of life with answers from 0, lowest grade, to 4, highest grade
Measured: 36 months
Incidence of Treatment-Emergent Adverse Events as assessed with mental status questionnaires
Survey with the questionnaire Mini Mental Status Examination (MMSE). A score of 24-30 indicates normal abilities, while a lower score indicates cognitive deficit.
Measured: 36 months
Periferic mononuclear blood cells (PMBC) subtypes predictive for disease progression and death
Identification of immune prognostic factors, studying lymphocyte subpopulations and their impact on the results obtained.
Measured: Form the start of radiotherapy up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2024
- Study start31 Aug 2024
- Primary completion28 Feb 2027 (estimated)
- Study completion28 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (34)Papers the sponsor has linked to this study.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by IRCCS San RaffaeleThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is study of feasibility in terms of toxicity of a dose escalation radiotherapy procedure, with 5 patients at each dose level, on 30 patients. The dose will be increased, moving to the next 5 patients, if no more than 1 acute toxicity of grade (G) 4 will be registered. The assumption is that the percentage of patients free from cumulative acute toxicity G≥3 (Common Terminology Criteria of Adverse Events-CTCAE- v5.0 scale) at 1 month after the end of treatment should not exceed 30%. A sample size of 30 patients results in a two-sided 95% confidence interval with a width of 0.328 (0.136-0.464) when the sample proportion is 0.300. Dropouts will be replaced by patients visited later, so as to reach the expected sample. Serum from 30 healthy volunteers, with sex and age characteristics comparable to the patients, will be collected to compare the level of immune biomarkers.
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS San Raffaele
- Sponsor type
- University, hospital or other
- Collaborators
- European Commission, Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale, Azienda Ospedaliera di Rilievo Nazionale e di Alta Specialità San Giuseppe Moscati (Avellino)
- Responsible party
- Principal investigator, Nadia Di Muzio, IRCCS San Raffaele
- Investigators
- Nadia G Di Muzio, Prof, Principal investigator, IRCCS San Raffaele Scientific Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06551909
- Sponsor's protocol ID
- PNRR-MCNT2-2023-12378239- Aim2
- Status last verified
- Oct 2026
- First submitted
- 12 Aug 2024
- Last updated
- 27 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The data that support the findings of this study (anonymized individual participant data) are available on request from the corresponding author to researchers who provide a methodologically sound proposal. Requests made to the corresponding author will be evaluated by the Lombardy Territorial Ethics Committee
Publications
Thust SC, Heiland S, Falini A, Jager HR, Waldman AD, Sundgren PC, Godi C, Katsaros VK, Ramos A, Bargallo N, Vernooij MW, Yousry T, Bendszus M, Smits M. Glioma imaging in Europe: A survey of 220 centres and recommendations for best clinical practice. Eur Radiol. 2018 Aug;28(8):3306-3317. doi: 10.1007/s00330-018-5314-5. Epub 2018 Mar 13.
PubMed 29536240Castellano A, Falini A. Progress in neuro-imaging of brain tumors. Curr Opin Oncol. 2016 Nov;28(6):484-493. doi: 10.1097/CCO.0000000000000328.
PubMed 27649026Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, Degroot J, Wick W, Gilbert MR, Lassman AB, Tsien C, Mikkelsen T, Wong ET, Chamberlain MC, Stupp R, Lamborn KR, Vogelbaum MA, van den Bent MJ, Chang SM. Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol. 2010 Apr 10;28(11):1963-72. doi: 10.1200/JCO.2009.26.3541. Epub 2010 Mar 15.
PubMed 20231676Laws ER, Parney IF, Huang W, Anderson F, Morris AM, Asher A, Lillehei KO, Bernstein M, Brem H, Sloan A, Berger MS, Chang S; Glioma Outcomes Investigators. Survival following surgery and prognostic factors for recently diagnosed malignant glioma: data from the Glioma Outcomes Project. J Neurosurg. 2003 Sep;99(3):467-73. doi: 10.3171/jns.2003.99.3.0467.
PubMed 12959431Brown TJ, Brennan MC, Li M, Church EW, Brandmeir NJ, Rakszawski KL, Patel AS, Rizk EB, Suki D, Sawaya R, Glantz M. Association of the Extent of Resection With Survival in Glioblastoma: A Systematic Review and Meta-analysis. JAMA Oncol. 2016 Nov 1;2(11):1460-1469. doi: 10.1001/jamaoncol.2016.1373.
PubMed 27310651Lacroix M, Abi-Said D, Fourney DR, Gokaslan ZL, Shi W, DeMonte F, Lang FF, McCutcheon IE, Hassenbusch SJ, Holland E, Hess K, Michael C, Miller D, Sawaya R. A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg. 2001 Aug;95(2):190-8. doi: 10.3171/jns.2001.95.2.0190.
PubMed 11780887Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. doi: 10.1056/NEJMoa043330.
PubMed 15758009Brandes AA, Franceschi E, Tosoni A, Blatt V, Pession A, Tallini G, Bertorelle R, Bartolini S, Calbucci F, Andreoli A, Frezza G, Leonardi M, Spagnolli F, Ermani M. MGMT promoter methylation status can predict the incidence and outcome of pseudoprogression after concomitant radiochemotherapy in newly diagnosed glioblastoma patients. J Clin Oncol. 2008 May 1;26(13):2192-7. doi: 10.1200/JCO.2007.14.8163.
PubMed 18445844Desai K, Hubben A, Ahluwalia M. The Role of Checkpoint Inhibitors in Glioblastoma. Target Oncol. 2019 Aug;14(4):375-394. doi: 10.1007/s11523-019-00655-3.
PubMed 31290002Gzell C, Back M, Wheeler H, Bailey D, Foote M. Radiotherapy in Glioblastoma: the Past, the Present and the Future. Clin Oncol (R Coll Radiol). 2017 Jan;29(1):15-25. doi: 10.1016/j.clon.2016.09.015. Epub 2016 Oct 13.
PubMed 27743773Valduvieco I, Verger E, Bruna J, Caral L, Pujol T, Ribalta T, Boget T, Oleaga L, Pineda E, Graus F. Impact of radiotherapy delay on survival in glioblastoma. Clin Transl Oncol. 2013 Apr;15(4):278-82. doi: 10.1007/s12094-012-0916-x. Epub 2012 Jul 24.
PubMed 22855197Burko P, D'Amico G, Miltykh I, Scalia F, Conway de Macario E, Macario AJL, Giglia G, Cappello F, Caruso Bavisotto C. Molecular Pathways Implicated in Radioresistance of Glioblastoma Multiforme: What Is the Role of Extracellular Vesicles? Int J Mol Sci. 2023 Mar 2;24(5):4883. doi: 10.3390/ijms24054883.
PubMed 36902314Tang Z, Dokic I, Knoll M, Ciamarone F, Schwager C, Klein C, Cebulla G, Hoffmann DC, Schlegel J, Seidel P, Rutenberg C, Brons S, Herold-Mende C, Wick W, Debus J, Lemke D, Abdollahi A. Radioresistance and Transcriptional Reprograming of Invasive Glioblastoma Cells. Int J Radiat Oncol Biol Phys. 2022 Feb 1;112(2):499-513. doi: 10.1016/j.ijrobp.2021.09.017. Epub 2021 Sep 14.
PubMed 34534627Pant A, Lim M. CAR-T Therapy in GBM: Current Challenges and Avenues for Improvement. Cancers (Basel). 2023 Feb 16;15(4):1249. doi: 10.3390/cancers15041249.
PubMed 36831591Weller M, van den Bent M, Preusser M, Le Rhun E, Tonn JC, Minniti G, Bendszus M, Balana C, Chinot O, Dirven L, French P, Hegi ME, Jakola AS, Platten M, Roth P, Ruda R, Short S, Smits M, Taphoorn MJB, von Deimling A, Westphal M, Soffietti R, Reifenberger G, Wick W. EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood. Nat Rev Clin Oncol. 2021 Mar;18(3):170-186. doi: 10.1038/s41571-020-00447-z. Epub 2020 Dec 8.
PubMed 33293629
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Radioimmunotherapy in Solid Tumors (Aim 2- Stereotactic Neoadjuvant Radiotherapy for Glioblastoma)
- ClinicalTrials.gov ID
- NCT06551909
- Acronym / sponsor ID
- PNRR-MCNT2-2023-12378239- Aim2
- Conditions
- Glioblastoma
- Keywords
- Glioblastoma, Neodjuvant Radiotherapy, Ultrahypofractionated Radiotherapy, Stereotactic Radiotherapy (SRT), Simultaneous Integrated Boost (SIB), Image Guidance
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- IRCCS San RaffaeleUniversity, hospital or other
- Collaborators
- European Commission, Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale, Azienda Ospedaliera di Rilievo Nazionale e di Alta Specialità San Giuseppe Moscati (Avellino)
- Study start
- 31 Aug 2024 (actual)
- Primary completion
- 28 Feb 2027 (estimated)
- Study completion
- 28 Feb 2027 (estimated)
- First posted
- 13 Aug 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.
This is a prospective multicenter study of hypofractionated radiotherapy for the radiation treatment (RT) of solid tumors and in particular for Glioblastoma (in Aim 2). It is based on the results of ongoing studies at our Institute to validate the efficacy of extremely hypofractionated RT in neoadjuvant settings, which observed immunostimulatory effects of RT and the synergy with immune components. The collaboration between San Raffaele Hospital (Milan), the IRCCS Istituto Nazionale dei Tumori Fondazione G. Pascale (Naples) and the San Giuseppe Moscati Hospital of National Relief and High Specialty (Avellino) will ensure that patient recruitment, treatment and monitoring can be translated into facilities of the National Health System using common procedures. The various departments involved will treat patients with the same methods synergistically exploring the immuno/biological factors related to efficacy (and/or toxicity), based on new radioimmunotherapeutic approaches. Clinical and research activity will be developed jointly, drawing on the expertise in radiotherapy, radiomics, oncology, imaging and immunotherapy skills already available.
Detailed description
This is a prospective multicenter pilot study. Functional and spectroscopic neuroradiological imaging will be adopted for treatment planning. Specialized software will be used to perform radiomic feature extraction and analysis of pre-trained neural networks from the advanced MRI (magnetic resonance imaging) and CT (computed tomography) used for simulation, to identify distribution patterns of aggressive and radioresistant disease areas, with higher probability of disease recurrence, and to intensify the dose on the areas identified as more aggressive, in order to counteract intrinsic radioresistance. The hypofractionated radiotherapy paradigm claims the benefit of reduced treatment times, improved quality of life, better access to specialized treatment centers and potentially improved tumor outcomes with greater disease control and less tumor repopulation. The rationale for neoadjuvant RT is based on the idea of counteracting the tumor's aggressive mechanisms with radiotherapy before the disease is surgically removed, in order to maximize the immunostimulatory potential of RT, and therefore reduce recurrences. Neoadjuvant treatment offers numerous advantages, first of all the ability to adjust the dose to the pathological volume identified by MRI and limit the volume of irradiated healthy brain tissue. Furthermore, the use of imaging derived from functional neuroradiological and spectroscopic techniques for treatment planning would allow us to increase the dose on the areas identified as more aggressive, in order act against intrinsic radioresistance. One of the major risks could be the possibility of developing radionecrosis, but this would not be a cause for concern in the neoadjuvant setting, as all irradiated tissue will then be surgically removed. Patients who agree to participate in the study and who would be candidates for radical surgical treatment, according to the evaluation of the Neurosurgery Department of our Institute, will be treated. These patients will receive neoadjuvant radiation treatment in 5 fractions delivering 30 Gy on PTV and 35-50 Gy on GTV, with a dose-escalation modality that involves increasing the dose to 35-40-42.5-45-47.5-50 Gy in groups of 5 consecutive patients, using standard chemotherapy (TMZ) after surgery.
Current diagnostic brain MRI allows a good definition of the initial disease and its most aggressive areas. Since relapses have always been found to occur in irradiated areas and recent studies have shown that reducing margins does not affect overall survival, smaller margins will be used from GTV to CTV and from CTV to PTV. Therefore, smaller volumes will be generated and treated with hypofractionation. Biological equivalent doses (BED) to the standard prescription will be delivered, with boost to a higher biological equivalent dose, in the most aggressive areas, in order to obtain better local control, maintaining an acceptable level of toxicity and therefore improve the evolution of the disease. CE marked devices (software) will be used according to the approved use, for the definition of the target (CT and MRI) and for the delivery of the treatment (linear accelerators) and the standard drug, which has the authorization for marketing, will be prescribed. Radiomic features related to local response and survival will be identified, to obtain a predictive model. At the same time, we will collect PMBC and patient serum in the biobank to identify presumed immunocorrelated of therapy efficacy and/or predictive biomarkers of response/toxicity to therapy. For comparative purposes, serum from healthy volunteers will also be collected, in numbers equivalent to patients and with sex and age characteristics comparable to the latter.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is study of feasibility in terms of toxicity of a dose escalation radiotherapy procedure, with 5 patients at each dose level, on 30 patients. The dose will be increased, moving to the next 5 patients, if no more than 1 acute toxicity of grade (G) 4 will be registered. The assumption is that the percentage of patients free from cumulative acute toxicity G≥3 (Common Terminology Criteria of Adverse Events-CTCAE- v5.0 scale) at 1 month after the end of treatment should not exceed 30%. A sample size of 30 patients results in a two-sided 95% confidence interval with a width of 0.328 (0.136-0.464) when the sample proportion is 0.300. Dropouts will be replaced by patients visited later, so as to reach the expected sample. Serum from 30 healthy volunteers, with sex and age characteristics comparable to the patients, will be collected to compare the level of immune biomarkers.
| Arm | Type | Receives |
|---|---|---|
| Treatment arm | Experimental | Radiation: Neoaddjuvant Stereotactic Radiotherapy with Simultaneous Integrated BoostThe 30 patients will receive neoadjuvant stereotactic radiotherapy in 5 fractions delivering 30 GY to PTV and 35-50 GY with Simultaneous Integrated Boost (SIB) to GTV using standard chemotherapy (TMZ) after surgery. GTV will be treated with escalating dose levels from 35 to 50 Gy. Patients will be divided into groups of 5 and will receive in the absence of 2 G4 toxicities per group, the following dose levels: 35-40-42.5-45-47.5 and 50 Gy |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Diagnosis of Glioblastoma.
- ECOG performance score 0-2 (defined during the first visit)
- Surgically removable lesion (according to the operability criteria established by the Neurosurgery Unit)
- For healthy volunteers, people who are as comparable as possible with the patient population in terms of sex and age will be recruited
Key exclusion criteria (2 listed)
- Previous stroke
- Presence of another primary and/or metastatic tumor For healthy volunteers also, absence of primary and/or metastatic tumor
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 |
|---|---|---|
| Neoaddjuvant Stereotactic Radiotherapy with Simultaneous Integrated BoostAlso: Ultrahypofractionated RadiotherapyPatients with Glioblastoma will receive neoadjuvant stereotactic radiotherapy to Planning Target Volume (PTV) to 30 Gy in 5 fractions, and a Simultaneous Integrated Boost delivering 35-50 GY to GTV. Patients will be divided into groups of 5 and will receive (in the absence of 2 G4 toxicities per group), the following dose levels: 35-40-42.5-45-47.5 and 50 Gy. Standard Temozolomide chemotherapy will be prescribed after surgery. | Radiation | Treatment arm |
Primary outcome
Acute toxicity
Time frame: one month
Incidence of acute toxicity of grade 3 or 4 as maximum toxicity value during the radiation treatment or in any case within a month of the end of SBRT, using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 scale (toxicity from 0- patients without toxicity to 5-death from toxicity)
12 secondary outcomes
Disease Free Survival
Time frame: From the date of radiotherapy end until the date of first documented clinical progression or date of death from any cause, whichever came first, assessed up to 36 months]
Cancer Specific Survival
Time frame: From the date of radiotherapy end until the date of first documented clinical progression or date of death from any cause, whichever came first, assessed up to 36 months]
Overall survival
Time frame: From the date of radiotherapy end until the date of death from any cause, assessed up to 36 months
Local Relapse Free Survival
Time frame: From the date of radiotherapy end until the date of local progression or date of death from any cause, whichever came first, assessed up to 36 months
Intracranial Relapse Free Survival
Time frame: From the date of radiotherapy end until the date of local progression or date of death from any cause, whichever came first, assessed up to 36 months
Extracranial Relapse Free Survival
Time frame: From the date of radiotherapy end until the date of local progression or date of death from any cause, whichever came first, assessed up to 36 months
Late toxicity
Time frame: From three months after the start of radiotherapy until the end of follow-up or death, assessed up to 36 months
Subacute Toxicity
Time frame: From one up to three months after the start of radiotherapy
Incidence of Treatment-Emergent Adverse Events as assessed with brain tumor specific quality of life questionnaires
Time frame: 36 months
Incidence of Treatment-Emergent Adverse Events as assessed with functional-social- emotional and general well being questionnaires
Time frame: 36 months
Incidence of Treatment-Emergent Adverse Events as assessed with mental status questionnaires
Time frame: 36 months
Periferic mononuclear blood cells (PMBC) subtypes predictive for disease progression and death
Time frame: Form the start of radiotherapy up to 6 months
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 27 Oct 2026.
- Results publication: PubMed 29536240Thust SC, Heiland S, Falini A, Jager HR, Waldman AD, Sundgren PC, Godi C, Katsaros VK, Ramos A, Bargallo N, Vernooij MW, Yousry T, Bendszus M, Smits M. Glioma imaging in Europe: A survey of 220 centres and recommendations for best clinical practice. Eur Radiol. 2018 Aug;28(8):3306-3317. doi: 10.1007/s00330-018-5314-5. Epub 2018 Mar 13.
- Results publication: PubMed 27649026Castellano A, Falini A. Progress in neuro-imaging of brain tumors. Curr Opin Oncol. 2016 Nov;28(6):484-493. doi: 10.1097/CCO.0000000000000328.
- Results publication: PubMed 20231676Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, Degroot J, Wick W, Gilbert MR, Lassman AB, Tsien C, Mikkelsen T, Wong ET, Chamberlain MC, Stupp R, Lamborn KR, Vogelbaum MA, van den Bent MJ, Chang SM. Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol. 2010 Apr 10;28(11):1963-72. doi: 10.1200/JCO.2009.26.3541. Epub 2010 Mar 15.
- Results publication: PubMed 12959431Laws ER, Parney IF, Huang W, Anderson F, Morris AM, Asher A, Lillehei KO, Bernstein M, Brem H, Sloan A, Berger MS, Chang S; Glioma Outcomes Investigators. Survival following surgery and prognostic factors for recently diagnosed malignant glioma: data from the Glioma Outcomes Project. J Neurosurg. 2003 Sep;99(3):467-73. doi: 10.3171/jns.2003.99.3.0467.
- Results publication: PubMed 27310651Brown TJ, Brennan MC, Li M, Church EW, Brandmeir NJ, Rakszawski KL, Patel AS, Rizk EB, Suki D, Sawaya R, Glantz M. Association of the Extent of Resection With Survival in Glioblastoma: A Systematic Review and Meta-analysis. JAMA Oncol. 2016 Nov 1;2(11):1460-1469. doi: 10.1001/jamaoncol.2016.1373.
- Results publication: PubMed 11780887Lacroix M, Abi-Said D, Fourney DR, Gokaslan ZL, Shi W, DeMonte F, Lang FF, McCutcheon IE, Hassenbusch SJ, Holland E, Hess K, Michael C, Miller D, Sawaya R. A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg. 2001 Aug;95(2):190-8. doi: 10.3171/jns.2001.95.2.0190.
- Results publication: PubMed 15758009Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. doi: 10.1056/NEJMoa043330.
- Results publication: PubMed 18445844Brandes AA, Franceschi E, Tosoni A, Blatt V, Pession A, Tallini G, Bertorelle R, Bartolini S, Calbucci F, Andreoli A, Frezza G, Leonardi M, Spagnolli F, Ermani M. MGMT promoter methylation status can predict the incidence and outcome of pseudoprogression after concomitant radiochemotherapy in newly diagnosed glioblastoma patients. J Clin Oncol. 2008 May 1;26(13):2192-7. doi: 10.1200/JCO.2007.14.8163.
- Results publication: PubMed 31290002Desai K, Hubben A, Ahluwalia M. The Role of Checkpoint Inhibitors in Glioblastoma. Target Oncol. 2019 Aug;14(4):375-394. doi: 10.1007/s11523-019-00655-3.
- Results publication: PubMed 27743773Gzell C, Back M, Wheeler H, Bailey D, Foote M. Radiotherapy in Glioblastoma: the Past, the Present and the Future. Clin Oncol (R Coll Radiol). 2017 Jan;29(1):15-25. doi: 10.1016/j.clon.2016.09.015. Epub 2016 Oct 13.
- Results publication: PubMed 22855197Valduvieco I, Verger E, Bruna J, Caral L, Pujol T, Ribalta T, Boget T, Oleaga L, Pineda E, Graus F. Impact of radiotherapy delay on survival in glioblastoma. Clin Transl Oncol. 2013 Apr;15(4):278-82. doi: 10.1007/s12094-012-0916-x. Epub 2012 Jul 24.
- Results publication: PubMed 36902314Burko P, D'Amico G, Miltykh I, Scalia F, Conway de Macario E, Macario AJL, Giglia G, Cappello F, Caruso Bavisotto C. Molecular Pathways Implicated in Radioresistance of Glioblastoma Multiforme: What Is the Role of Extracellular Vesicles? Int J Mol Sci. 2023 Mar 2;24(5):4883. doi: 10.3390/ijms24054883.
- Individual participant dataSharing planned: Yes. The data that support the findings of this study (anonymized individual participant data) are available on request from the corresponding author to researchers who provide a methodologically sound proposal. Requests made to the corresponding author will be evaluated by the Lombardy Territorial Ethics Committee
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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.
Nadia G Di Muzio, Prof principal investigator
IRCCS San Raffaele Scientific Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Neoaddjuvant Stereotactic Radiotherapy with Simultaneous Integrated Boost in people with Glioblastoma, run by IRCCS San Raffaele at 1 site in Italy.
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 2 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 27 Oct 2026. 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 Italy. 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.
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 Nadia G Di Muzio, Prof (+390226437643, dimuzio.nadia@hsr.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Acute toxicity (time frame: one month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06551909, which also lists 34 linked publications.
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 27 Oct 2026.