Craniospinal Irradiation in Histone AlteRed Midline Glioma

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Craniospinal Irradiation in Histone AlteRed Midline Glioma

Study Purpose

Paediatric H3K27/H3G34 mutant diffuse midline gliomas are high grade gliomas that arise in midline structures/cerebral hemispheres and are known to have dismal outcomes. Standard treatment includes definitive radiation therapy to primary site along with concurrent temozolomide chemotherapy following histological confirmation with a biopsy. Studies have shown poorer outcomes in the paediatric age group compared to that of adults and an increased risk to fail/recur in the leptomeninges(covering of brain and spinal cord). The following study is planned in order to assess the benefit of craniospinal irradiation(delivering radiotherapy to brain, spinal cord and its covering membrane in this high risk population. Thereby the investigator aim to improve survival in newly diagnosed histone mutant pediatric midline gliomas in the upfront setting. Patterns of disease failure, treatment related toxicities and quality of life will also be assessed as a part of this study. If proven beneficial, this study will influence how patients with this diagnosis will be treated in the future.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	3 Years - 18 Years
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Newly diagnosed biopsy proven histone altered diffuse midline glioma. 2. Age- ≥3 to <18 years at time of diagnosis. 3. Karnofsky/Lansky Performance Score more than or equal to 70. 4. Has provided written informed consent/ assent form. 5. No prior therapy except debulking surgery or biopsy.

Exclusion Criteria:

1. Recurrent or progressive disease. 2. Clinical features or family history suggestive of Inherited Cancer Predisposition such as Constitutional Mismatch Repair Deficiency (CMMRD) 3. Previous history of malignancy. 4. Not willing /unlikely to comply with proposed therapy and follow up

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT06720727
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	N/A
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Tata Memorial Centre
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Abhishek Chatterjee, MD
Principal Investigator Affiliation	Tata Memorial Hospital
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	India
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Glioma

Additional Details

Introduction: Paediatric H3K27/H3G34 mutant diffuse midline gliomas (DMGs) are aggressive high-grade gliomas predominantly affecting midline structures and cerebral hemispheres. Despite aggressive therapy including radiation and chemotherapy, these tumors carry a poor prognosis, particularly in children, with frequent recurrence and high risk of leptomeningeal spread. Current standard treatment involves definitive radiation therapy to the primary site and concurrent temozolomide chemotherapy following histological confirmation via biopsy. However, outcomes remain suboptimal, prompting exploration of more intensive therapeutic strategies. Primary objective: To study if the addition of craniospinal irradiation to standard practice improves outcomes in pediatric diffuse midline glioma. Secondary objectives:

- Estimate median time to leptomeningeal dissemination and compare with historical control.

- Study patterns of failure.

- Early and late toxicities.

- Study quality of life indices.

- To estimate QTWiST (Quality of life without symptoms or toxicity) Primary endpoint: Overall survival at 12 months.

Secondary endpoints:

- Time to leptomeningeal dissemination in months.

- Incidence of different failure patterns from clinico-radiological assessment.

- Toxicity assessment with the NCI Common Terminology Criteria for Adverse Events version 5 (CTCAE v5) during CSI(weekly), at conclusion of radiotherapy , post completion of 6 cycles adjuvant temozolomide, and in subsequent follow-ups at 3, 6, 9 and 12 months.

- Quality of life indices using the EORTC QLQC- 30 and its BN -20 module at baseline, after completion of radiotherapy, post completion of 6 cycles adjuvant temozolomide and in subsequent follow-up visits at 3, 6, 9 and 12 months.

- Quality of life without symptoms or toxicity in three health states TOX (toxicity), TWIST (time without symptoms) and REL (relapse) at baseline, after completion of radiotherapy, post completion of 6 cycles adjuvant temozolomide and in subsequent follow-up visits at 3, 6, 9 and 12 months.

Study setting: The study will be conducted in the department of Radiation Oncology, Neuro Oncology Disease management group

Arms & Interventions

Arms

Experimental: Single arm

Craniospinal irradiation involves delivery of radiation therapy to the whole brain, spinal cord, nerve roots, the covering meninges(leptomeninges) and subarachnoid space and provides a viable means of mitigating leptomeningeal spread and possibly improving survival.

Interventions

Radiation: - craniospinal irradiation

Delivering radiotherapy to brain, spinal cord and its covering membrane.

Contact a Trial Team

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