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

Stereotactic Biopsy Split-Course Radiation Therapy - Diffuse Midline Glioma (SPORT-DMG)

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.

Study Overview

• Status: Recruiting
• Conditions: Diffuse Midline Glioma, H3 K27M-Mutant
• Intervention / Treatment: Other: Questionnaire Administration; Procedure: Magnetic Resonance Imaging; Radiation: Hypofractionated Radiation Therapy; Procedure: Computed Tomography Scan

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 is superior to the low-end historical control (Survival rate of 40% at 10 months when calculating from time of enrollment) 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, calculated from date of registration and separately from primary tumor diagnosis date.

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 from date of enrollment to death and from primary tumor diagnosis date to death.

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 computed tomography (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 Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Recruiting
      • Mayo Clinic Hospital in Arizona
      • Principal Investigator: Safia K. Ahmed, M.D.
      • Contact: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic in Rochester
      • Contact: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
      • Principal Investigator: Roman O. Kowalchuk, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

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

  • NOTE: All novel therapeutic interventions, including but not limited to dordaviprone, are allowed for patients who enroll on the clinical trial

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (hypofractionated RT); Patients undergo hypofractionated RT over 10 fractions. Patients who achieve progression undergo up to 2 retreatment courses. Patients undergo MRI and CT scan throughout the study.

Other: Questionnaire Administration; Ancillary studies; Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Medical Imaging; Magnetic Resonance / Nuclear Magnetic Resonance; nuclear magnetic resonance imaging; Magnetic Resonance Imaging (MRI); sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Radiation: Hypofractionated Radiation Therapy; Undergo hypofractionated radiation therapy; Other Names: Hypofractionated Radiotherapy; hypofractionation; Radiation, Hypofractionated; Hypofractionated; Procedure: Computed Tomography Scan; Undergo CT scan; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to progression	Defined as the time from date of diagnosis to the date of radiographic or clinical progression following second course of hypofractionated radiation therapy.	At 10 months
Overall Survival (OS) at 10 months	OS is defined as the time from date of study registration until death due to any cause.	Up to 6 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	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.	Up to 3 years
Quality of Life Measurement - PedsQL (children under 18)	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.	Baseline up to 3 years
Quality of Life Measurement - NFBrSI-24	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).	Baseline up to 3 years
Progression free survival	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.	Up to 3 years
FACT-General Family/Caregiver Questionnaire (FACT-G)	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.	Up to 3 years
Overall survival	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.	Up to 3 years
Time to second progression	Defined as the time date of registration or primary tumor diagnosis to the date of radiographic, clinical progression, or death following second course of hypofractionated radiation therapy.	Up to 6 years

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Roman O. Kowalchuk, MD, Mayo Clinic in Rochester

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2021
• Primary Completion (Estimated): October 15, 2027
• Study Completion (Estimated): October 15, 2027

Study Registration Dates

• First Submitted: October 1, 2021
• First Submitted That Met QC Criteria: October 1, 2021
• First Posted (Actual): October 14, 2021

Study Record Updates

• Last Update Posted (Actual): July 14, 2026
• Last Update Submitted That Met QC Criteria: July 10, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: DIPG; H3K27M; Diffuse Midline Glioma; DMG
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma; Investigative Techniques; Therapeutics; Physical Phenomena; Chemistry Techniques, Analytical; Spectrum Analysis; Electromagnetic Phenomena; Magnetic Phenomena; Radiotherapy; Electromagnetic Radiation; Radiation, Ionizing; Dose Fractionation, Radiation; Radiotherapy Dosage; Radiation; Magnetic Resonance Spectroscopy; X-Rays; Radiation Dose Hypofractionation
• Other Study ID Numbers: GMROR2162 (Mayo Clinic in Rochester); 21-000069 (Other Identifier: Mayo Clinic Institutional Review Board)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No