A Phase-1 Trial to Investigate the Use of Pulsed Low-dose Rate Radiotherapy in Diffuse Midline Gliomas. (BABY-PULSAR)

October 29, 2026 updated by: Centro di Riferimento Oncologico - Aviano

Over the past decades, advances in radiation therapy technology have significantly reduced treatment-related toxicity. In patients with diffuse midline glioma (DMG), these improvements have enhanced the tolerability of radiotherapy but have not improved disease control. Pulsed low-dose-rate radiotherapy (pLDRT) may offer additional advantages by further reducing treatment-related toxicity, preserving tumor vascularization to facilitate the delivery and efficacy of subsequent chemotherapy, and exploiting the low-dose hyper-radiosensitivity phenomenon. To the best of our knowledge, no clinical studies have evaluated pLDRT in patients with DMG. Therefore, the primary objective of this phase I study is to evaluate the tolerability of pLDRT in this predominantly pediatric population and to determine a safe dose level for future clinical investigation.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Over the past decades, advances in radiation therapy technology have significantly reduced treatment-related toxicity. In patients with diffuse midline glioma (DMG), these improvements have enhanced the tolerability of radiotherapy but have not improved disease control. Pulsed low-dose-rate radiotherapy (pLDRT) may offer additional advantages by further reducing treatment-related toxicity, preserving tumor vascularization to facilitate the delivery and efficacy of subsequent chemotherapy, and exploiting the low-dose hyper-radiosensitivity phenomenon. To the best of our knowledge, no clinical studies have evaluated pLDRT in patients with DMG. Therefore, the primary objective of this phase I study is to evaluate the tolerability of pLDRT in this predominantly pediatric population and to determine a safe dose level for future clinical investigation.

Study Type

Interventional

Enrollment (Estimated)

12

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Elisa Coassin, MD
  • Phone Number: +39 0434 659632
  • Email: ecoassin@cro.it

Study Locations

  • Italy
    • Pordenone
      • Aviano, Pordenone, Italy, 33081
        • Recruiting
        • Centro di Riferimento Oncolgico -IRCCS
        • Contact:
        • Principal Investigator:
          • Elisa Coassin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 second to 100 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Radiological and/or histological diagnosis of diffuse midline glioma (DMG).
  • Ability to maintain the treatment position or undergo sedation, if required.
  • Written informed consent provided by the parent(s) or legal guardian(s), or by the patient if aged ≥18 years.

Exclusion Criteria:

  • Refusal to undergo radiotherapy (i.e., lack of signed informed consent).
  • Concurrent chemotherapy.
  • Leptomeningeal dissemination of disease.
  • Ongoing pregnancy (for post-pubertal female patients).
  • Previous radiotherapy to the brainstem.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Determination of the safe dose level of pulsed low-dose-rate radiotherapy (pLDRT)
Radiation: Pulsed Low-Dose-Rate Radiotherapy, pLDRT

The radiotherapy treatment will preferably be delivered using volumetric modulated arc therapy (VMAT) with high-energy photons (6 MV), including 6 MV flattening filter-free (FFF) beams when appropriate. In selected cases, intensity-modulated radiotherapy (IMRT) may be used.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determination of the safe dose level of pulsed low-dose-rate radiotherapy (pLDRT)
Time Frame: Up to 5 years

Incidence of grade ≥3 toxicities, as defined according to the CTCAE v5.0 scale
Up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To evaluate the median time to local disease progression.
Time Frame: Up to 5 years

Median progression-free survival (PFS) defined as the time from treatment initiation to the first documented disease progression or death from any cause. Disease progression will be defined according to the RAPNO criteria for pediatric patients and the RANO criteria for adult patients.
Up to 5 years
To evaluate median overall survival.
Time Frame: Up to 5 years

Median overall survival (OS), defined as the time from treatment initiation to death from any cause.
Up to 5 years
To assess the incidence of treatment-related toxicities other than dose-limiting toxicities.
Time Frame: Up to 5 years

Frequency of neurological toxicities
Up to 5 years
To assess changes in neurological symptoms compared with baseline.
Time Frame: Up to 5 years

Change in frequencies of neurological symptoms
Up to 5 years
To evaluate corticosteroid use during radiotherapy.
Time Frame: Up to 5 years

Dexamethasone dose (mg/day) mean
Up to 5 years
To evaluate circulating prognostic and predictive biomarkers of response to pLDRT.
Time Frame: Up to 5 years

Relation between PFS (defined as the time from treatment initiation to the first documented disease progression or death from any cause) and levels of circulating biomarkers will be evaluated with Kaplan-Meyer method
Up to 5 years
To evaluate circulating prognostic and predictive biomarkers of response to pLDRT.
Time Frame: Up to 5 years

Relation between OS (defined as the time from treatment initiation to death from any cause) and levels of circulating biomarkers will be evaluated with Kaplan-Meyer method
Up to 5 years
To evaluate tissue biomarkers of response to pLDRT.
Time Frame: Up to 5 years

Relation between PFS (defined as the time from treatment initiation to the first documented disease progression or death from any cause) and levels of tissue biomarkers will be evaluated with Kaplan-Meyer method
Up to 5 years
To evaluate tissue biomarkers of response to pLDRT.
Time Frame: Up to 5 years

Relation between OS (defined as the time from treatment initiation to death from any cause) and levels of tissue biomarkers will be evaluated with Kaplan-Meyer method
Up to 5 years
To characterize the inflammatory and immune profile induced by the pLDRT treatment schedule.
Time Frame: Up to 5 years

Mean of median levels of biomarkers of inflammatory and immune profile
Up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centro di Riferimento Oncologico - Aviano

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 13, 2026

Primary Completion (Estimated)

July 15, 2030

Study Completion (Estimated)

July 15, 2030

Study Registration Dates

First Submitted

October 29, 2026

First Submitted That Met QC Criteria

October 29, 2026

First Posted (Actual)

November 5, 2026

Study Record Updates

Last Update Posted (Actual)

November 5, 2026

Last Update Submitted That Met QC Criteria

October 29, 2026

Last Verified

October 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CRO-2025-21

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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