Stereotactic Biopsy Split-Course Radiation Therapy in Diffuse Midline Glioma, SPORT-DMG Study

Phase 2

Recruiting

• Conditions: Diffuse Midline Glioma, H3 K27M-Mutant
• Interventions: Radiation: Hypofractionated Radiation Therapy; Other: Questionnaire Administration; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography and Computed Tomography Scan

• Registration Number: NCT05077735
• Lead Sponsor: Mayo Clinic

Brief Summary

This phase II trial studies the clinical outcomes of hypofractionated radiation therapy in patients with diffuse midline gliomas. This study aims to change the way radiation is delivered, from giving 6 weeks of radiation all at once to giving 2 weeks of radiation. This may determine if there is a difference in the outcome of the treatment, and most importantly, the patients' quality of life.

Detailed Description

PRIMARY OBJECTIVE:

I. To determine that 10-month overall survival (OS) rate for the hypofractionated radiation course of 25 Gy in 10 fractions in patients with diffuse midline glioma of the pons isn't inferior to the historical control (survival rate of 50% at 10 months) based on the current standard of care (54 GY in 30 fractions).

SECONDARY OBJECTIVES:

I. To evaluate the quality of life outcomes for patients with diffuse midline gliomas of the pons.

II. To estimate the time to progression after the second hypofractionated radiation course of 25 Gy in 10 fractions in patients with diffuse midline glioma of the pons, calculated from date of diagnosis.

III. To estimate progression free survival intervals for patients after each hypofractionated radiation treatment course.

IV. To evaluate the quality of life outcomes for parents of patients =\< 18 years with the Functional Assessment of Cancer Therapy General (FACT-G) Family/Caregiver Questionnaire.

V. To estimate the overall survival for patients with diffuse midline gliomas of the pons treated with planned multi-course hypofractionated radiation courses.

VI. To report toxicities associated with hypofractionated, planned, multi-course radiation treatment for diffuse midline glioma of the pons.

OUTLINE:

Patients undergo hypofractionated radiation therapy (RT) over 10 fractions. Patients who experience progression undergo up to 2 retreatment courses. Patients undergo magnetic resonance imaging (MRI) and positron emission tomography- computed tomography (PET-CT) scan throughout the study.

After completion of study treatment, patients are followed up at 1 month, every 2 months for year 1, every 3 months for year 2, then every 6 months for year 3.

Study Timeline

• Study First Submitted: 2021-10-01
• Study First Submitted QC: 2021-10-01
• Study Start: 2021-10-11
• Study First Posted: 2021-10-14
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-31
• Last Update Posted: 2025-01-03
• Primary Completion: 2027-10-15
• Study Completion: 2027-10-15

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 29

Inclusion Criteria

• Age >= 1 year(s) old (no maximum age)

• Radiologic appearance of diffuse midline glioma of the pons, including diffuse infiltration of >= 50% of the pons on MRI, with or without extension to the midbrain and/or medulla oblongata with at least 1 of the 3 brainstem symptoms (cranial nerve deficit, long tract sign, or cerebellar sign)

  • If all features of this clinicoradiologic criteria are met, then patients can continue on protocol with or without a biopsy
  • If all features of this clinicoradiologic criteria are not met, patients must receive a brainstem lesion biopsy to be treated on protocol. If this cannot be completed, patients will be withdrawn from the study
  • If biopsy has already been completed at an outside institution, the outside pathology report will be reviewed ahead of trial enrollment. The pathology specimen will then be sent to Mayo Clinic for further review, but will not delay study enrollment

• Able to undergo MRI Brain

• Negative urine pregnancy test completed =< 7 days prior to registration, for women of childbearing potential only

• Primary language of English or Spanish for patients and their caregiver

• Patient or caregiver willing and able to provide written informed consent

• Caregiver able to complete questionnaires by themselves or with assistance

• Willing to return to enrolling institution for follow-up during the active monitoring phase of the study

Read More

Exclusion Criteria

• Any patient who has received previous radiation to the brain

• Any patient who has received previous chemotherapy

• Any patient with a diagnosis of neurofibromatosis type 1 or 2 (NF1 or NF2)

• Any of the following:

  • Pregnant women
  • Nursing women
  • Women of childbearing potential who are unwilling to employ adequate contraception

• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Other active malignancy =< 5 years prior to registration. EXCEPTIONS: Non-melanotic skin cancer, breast cancer, prostate cancer, well-differentiated thyroid cancer, carcinoma-in-situ of the cervix

  • NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer

• Patients > 16 years with an Eastern Cooperative Oncology Group (ECOG) score >= 4 and patients =< 16 years with a Lansky play scale =< 20

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (hypofractionated RT)	Magnetic Resonance Imaging	Patients undergo hypofractionated RT over 10 fractions. Patients who achieve progression undergo up to 2 retreatment courses. Patients undergo MRI and PET-CT scan throughout the study.
Treatment (hypofractionated RT)	Positron Emission Tomography and Computed Tomography Scan	Patients undergo hypofractionated RT over 10 fractions. Patients who achieve progression undergo up to 2 retreatment courses. Patients undergo MRI and PET-CT scan throughout the study.
Treatment (hypofractionated RT)	Hypofractionated Radiation Therapy	Patients undergo hypofractionated RT over 10 fractions. Patients who achieve progression undergo up to 2 retreatment courses. Patients undergo MRI and PET-CT scan throughout the study.
Treatment (hypofractionated RT)	Questionnaire Administration	Patients undergo hypofractionated RT over 10 fractions. Patients who achieve progression undergo up to 2 retreatment courses. Patients undergo MRI and PET-CT scan throughout the study.

Primary Outcome Measures

Name	Time	Method
Time to progression	From date of diagnosis to the date of radiographic or clinical progression following second course of hypofractionated radiation therapy, assessed up to 3 years	The Wilcoxon Signed-Rank Tests for Non-Inferiority was utilized from PASS software for this design.

Secondary Outcome Measures

Name	Time	Method
Quality of Life Measurement - PedsQL (children under 18)	Baseline up to 3 years	Results from Pediatric Quality of Life Inventory (PedsQL) Brain Tumor Module will be used to evaluate the quality of life outcomes in patients up to 18 years old. PedsQL™ assessments include 23 items answered on aLikert response scale (0=never a problem; 1=almost never a problem; 2=sometimes a problem; 3=often a problem; 4=almost always a problem) for each item.
Quality of Life Measurement - NFBrSI-24	Baseline up to 3 years	The National Comprehensive Cancer Network (NCCN)-Functional Assessment of Cancer Therapy (FACT)-Brain Symptom Index-24 (NFBrSI-24) will be used in patients more than 18 years old. Changes in raw score from baseline to each time-point will be assessed in each of the physical and mental health domains. The NFBrSI-24 consists of 24 questions assessing symptoms over the past 7 days. Items are scored on a 5-point Likert type scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much).
Progression free survival	Up to 3 years	The average progression free survival interval after each course of RT will be reported in months. Progression free survival is defined as the time from registration date to the earliest date of documentation of progression after each course of radiation therapy (RT) or death due to any cause.
FACT-General Family/Caregiver Questionnaire (FACT-G)	Up to 3 years	Changes in raw score from baseline to each time-point will be assessed in each of the physical and mental health domains. The FACT-G contains 27 questions within 4 subscale domains \[Physical Well-Being, Social/Family Well-Being, Emotional Well-Being, Functional Well-Being\] related to health-related quality of life (QOL) in the past 7 days, with higher scoring indicating better QOL.
Overall survival	Up to 3 years	Overall survival is defined as the time from registration date to death due to any cause. Patients alive at the date of last contact will be censored.
Incidence of adverse events	Up to 3 years	The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.

Trial Locations

Locations (2)

Mayo Clinic Hospital in Arizona; 🇺🇸 Phoenix, Arizona, United States

Mayo Clinic in Rochester; 🇺🇸 Rochester, Minnesota, United States