Radioimmunotherapy in Solid Tumors (PNRR-MCNT2-2023-12378239-Aim2)

NCT06551909 | Recruiting DMC

• 1 other identifier: PNRR-MCNT2-2023-12378239- Aim2
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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, 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.

Conditions

Glioblastoma

Keywords

Glioblastoma; Neodjuvant Radiotherapy; Ultrahypofractionated Radiotherapy; Stereotactic Radiotherapy (SRT); Simultaneous Integrated Boost (SIB); Image Guidance

Outcome Measures

Primary Outcomes (1)

• 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)

  one month

Secondary Outcomes (12)

• Disease Free Survival

  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

  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

  From the date of radiotherapy end until the date of death from any cause, assessed up to 36 months

• Local Relapse Free Survival

  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

  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

Other Outcomes (2)

• Radiomics

  36 months

• Predictive factors for disease progression and death

  From radiotherapy end to date of local, regional progression, distant failure, or death, assessed up to 36 months

Study Arms (1)

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

Radiation: Neoaddjuvant Stereotactic Radiotherapy with Simultaneous Integrated Boost

Interventions

Neoaddjuvant Stereotactic Radiotherapy with Simultaneous Integrated Boost RADIATION

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.

Also known as: Ultrahypofractionated Radiotherapy

Treatment arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Previous stroke
• Presence of another primary and/or metastatic tumor For healthy volunteers also, absence of primary and/or metastatic tumor

Sponsors & Collaborators

• IRCCS San Raffaele: lead
• European Commission: collaborator
• Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale: collaborator
• Azienda Ospedaliera di Rilievo Nazionale e di Alta Specialità San Giuseppe Moscati (Avellino): collaborator

Study Sites (1)

IRCCS San Raffaele Scientific Institute

Milan, MI, 20132, Italy

RECRUITING

Related Publications (33)

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MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Nadia G Di Muzio, Prof

  IRCCS San Raffaele Scientific Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nadia G Di Muzio, Prof

CONTACT

+390226437643; dimuzio.nadia@hsr.it

Andrei Fodor, MD

CONTACT

+390226437634; fodor.andrei@hsr.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: 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.

Study Record Dates

• First Submitted: August 12, 2024
• First Posted: August 13, 2024
• Study Start: August 31, 2024
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): February 28, 2027
• Last Updated: June 8, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: for 2 years after the end of the study
• Access Criteria: request from the corresponding author approved by the Lombardy Territorial Ethics Committee

Locations

IT (1)