Craniospinal Irradiation in Histone AlteRed Midline Glioma

Not Applicable

Recruiting

• Conditions: Glioma

• Registration Number: NCT06720727
• Lead Sponsor: Tata Memorial Centre

Brief Summary

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.

Detailed Description

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

Study Timeline

• Study First Submitted: 2024-10-30
• Study First Submitted QC: 2024-12-02
• Study First Posted: 2024-12-06
• Status Verified: 2025-01
• Study Start: 2025-01-03
• Last Update Submitted: 2025-01-16
• Last Update Posted: 2025-01-20
• Primary Completion: 2028-11-08
• Study Completion: 2028-11-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 32

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Survival Outcomes	at 12 months	Overall survival- time in months between the date of diagnosis to date of death due to any cause

Secondary Outcome Measures

Name	Time	Method
Leptomeningeal Dissemination	at 12 months	Time to leptomeningeal dissemination (will be defined as time in months between completion of planned therapy to the date of confirmation of leptomeningeal metastasis)
Patterns of failure	at 12 months	Incidence of different patterns of failure from diagnosis ( the time point of measurement of the primary outcome - overall survival
Any treatment emergent acute toxicity recording	Baseline , week 1 , week 2 , week 3 , week 4 , week 5 ,week 6 , conclusion of RT	All treatment emergent acute toxicity- expected (nausea, vomiting, hematological, dermatitis and mucositis) and unexpected, will be recorded.; Grading will be done for all using the Common Terminology Criteria for Adverse Events (CTCAE) Version 5
Quality of life indices	will be done at 3 months	Objective scoring with European Organisation For Research And Treatment Of Cancer(EORTC) Quality of Life Questionnaire(QLQC-30), brain specific module (BN 20)
QTWiST (Quality of life Without Symptoms or Toxicity) calculation	will be done at 3 months	Objective score calculation using mean duration in each health state weighed by a utility coefficient; from QLQC 30- BN 20 scores and the time spent in serious toxicity and without relapse.
Any treatment emergent late toxicity recording	After completion of 6 cycles of adjuvant chemotherapy, at 3months, 6months, 9months and 12months follow up	All treatment emergent late toxicity- expected and unexpected, will be recorded after completion of chemotherapy. Grading will be done for all using the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.

Trial Locations

Locations (1)

Tata Memorial Hospital; 🇮🇳 Mumbai, India