Temporally-modulated Pulsed Radiation Therapy (TMPRT) After Prior EBRT for Recurrent IDH-mutant Gliomas

A Pilot Study of Temporally-modulated Pulsed Radiation Therapy to Reirradiate Recurrent IDH-mutant Gliomas After Prior External Beam Radiation Therapy

This clinical trial studies the side effects of temporally-modulated pulsed radiation therapy (TMPRT) in patients with IDH-mutant gliomas who have previously received radiation therapy to the brain. TMPRT is a radiation technique in which radiation is delivered in multiple small doses on a specific timed interval, instead of delivering one large dose at one time. This technique may improve efficacy while reducing toxicity and improving patient quality of life.

Study Overview

• Status: Recruiting
• Conditions: Astrocytoma; Glioma, Malignant; Oligodendroglioma, Adult
• Intervention / Treatment: Radiation: temporally-modulated pulsed radiotherapy (TMPRT)

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jiayi Huang, M.D.; Phone Number: 314-273-2931; Email: jiayi.huang@wustl.edu

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
      • Principal Investigator: Jiayi Huang, M.D.
      • Sub-Investigator: Stephanie Perkins, M.D.
      • Sub-Investigator: Chris Abraham, M.D.
      • Sub-Investigator: Milan Chheda, M.D.
      • Sub-Investigator: Clifford Robinson, M.D.
      • Contact: Jiayi Huang, M.D.; Phone Number: 314-273-2931; Email: jiayi.huang@wustl.edu
      • Sub-Investigator: Michael Prusator, Ph.D.
      • Sub-Investigator: Yi Huang, M.S.
      • Sub-Investigator: Omar Butt, M.D., Ph.D.
      • Sub-Investigator: Shahed Badiyan, M.D.
      • Sub-Investigator: George Ansstas, M.D.
      • Sub-Investigator: Tanner Johanns, M.D., Ph.D.
      • Sub-Investigator: Nikhil Rammahon, M.D. Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed recurrent IDH-mutant gliomas (either astrocytoma or oligodendroglioma) with prior external beam radiation therapy (EBRT) to the same region. The recurrent tumor may be either histologically confirmed or based on clinical assessment. Any number of prior recurrences is allowed.
• Maxium tumor diameter of 7 cm or less.
• Prior EBRT is ≥ 2 years ago.
• The region for reirradiation should have received at least 45 Gy from the prior EBRT but no more than 75 Gy. The prior EBRT could be either photon-based or proton-based.
• Prior SRS to the same region is permitted as long as the cumulative dose of EBRT plus SRS is no more than 75 Gy. The prior SRS should be completed at least 6 months ago.
• Life expectancy ≥ 12 months
• At least 18 years of age.
• Karnofsky performance status (KPS) of at least 70%.
• Females of childbearing potential (defined as a female who is non-menopausal or surgically sterilized) must be willing to use an acceptable method of birth control (i.e., hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
• Able to understand and willing to sign an IRB-approved written informed consent document (legally authorized representative permitted).

Exclusion Criteria:

• Leptomeningeal or metastatic involvement.
• Prior history of grade 3 or higher radiation necrosis that is at least possibly related to prior radiotherapy.
• Use of concurrent bevacizumab or other anti-VEGF-directed therapy during TMPRT is not allowed. If the patient is on bevacizumab, the patient needs to discontinue bevacizumab for at least 4 weeks prior to the start of TMPRT and remain stable. Other chemotherapy, immunotherapy, or target therapy can be used concurrently or adjuvantly at the discretion of treating physician.
• Medical contraindication to MRI (e.g., unsafe foreign metallic implants, incompatible pacemaker, inability to lie still for long periods, severe to end-stage kidney disease or on hemodialysis).
• Pregnant.

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: Arm 1: temporally-modulated pulsed radiotherapy (TMPRT); Patients receive TMPRT daily as 10 pulses of 0.2 Gy each with a 3-minute interval between pulses (effective dose rate = 0.0667 Gy/min) to a total dose of 54 Gy at 2 Gy per day. Treatment continues for a total of 27 fractions in the absence of disease progression or unacceptable toxicity.	Radiation: temporally-modulated pulsed radiotherapy (TMPRT); Intensity modulated RT (IMRT) using single or two arc therapy will be used for RT delivery.; Other Names: pulsed low-dose-rate RT (PLRT); pulsed reduced-dose-rate RT (PRRT)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative incidence of grade 3 or higher reirradiation-related central nervous system adverse events	Adverse events are graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0	From start of treatment through 1 year
Frequency of acute intolerable toxicities	Intolerable toxicities are defined as grade 3 or higher central nervous system (CNS) adverse events at least possibly related to radiation as graded by the Common Terminology Criteria for Adverse Events v5.0 with the exception of grade 3 fatigue, headache, nausea, and vomiting. Any serious adverse event leading to discontinuation of TMPRT that is at least possibly related will be considered an intolerable toxicity.	From start of treatment through 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in symptom burden as measured by M.D. Anderson Symptom Inventory - Brain Tumor (MDASI-BT)	The MDASI-BT consists of 23 symptom questions asking the patient to rate the severity of their symptoms in the last 24 hours. The range is an 11-point scale (0 to 10), with 0 being "not present" and 10 being "as bad as you can imagine". The symptom composite score is the average of the symptoms items, and the score ranges from 0 to 23 with a higher score indicating more severe symptoms. Symptom burden deterioration is defined as an increase of more than 1 point from baseline on the composite symptom scale.	Assessed at approximately 3 months, 6 months, and 12 months after start of treatment
Change in interference as measured by M.D. Anderson Symptom Inventory - Brain Tumor (MDASI-BT)	The MDASI-BT consists of 6 interference questions asking the participant to rate how their symptoms interfered with how they felt and functioned in the last 24 hours. The range is an 11-point scale (0 to 10), with 0 being "did not interfere" and 10 being "interfered completely". The interference composite score is the average of the 6 items on interferences, with a higher score indicating more interference. Interference deterioration is defined as an increase of more than 1 point from the baseline on the interference score.	Assessed at approximately 3 months, 6 months, and 12 months after start of treatment
Change in quality of life (QOL) as measured by self-reported QOL on the Linear Analog Scale Assessment (LASA)	The LASA is a single-item questionnaire that asks the participants to rate their overall quality of life. The LASA scale runs from 0 (as bad as it can be) to 10 (as good as it can be).	Assessed at approximately 3 months, 6 months, and 12 months after start of treatment
Progression-free survival (PFS)	PFS is defined as the time from start of treatment until time of disease progression or death from any cause. Progression will be evaluated per standard clinical care based on the Response Assessment in Neuro-Oncology (RANO) criteria for low-grade glioma (van dent Bent et al., 2011).	At one year after start of treatment
Overall survival (OS)	OS is defined as the time from start of treatment until the date of death due to any cause.	At one year after start of treatment
Number of reirradiation adverse events		From start of treatment through month 12 follow-up

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative changes of different subtypes of circulating T-cells	Blood will be collected before the start of TMPRT and at week 6 of radiation therapy to assess for changes in circulating T-cells.	At baseline and week 6 of radiation therapy.
Relative changes of different subtypes of myeloid cells	Blood will be collected before the start of TMPRT and at week 6 of radiation therapy to assess for changes in myeloid cells.	At baseline and week 6 of radiation therapy.

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Jiayi Huang, M.D., Washington University School of Medicine

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2022
• Primary Completion (Estimated): June 28, 2027
• Study Completion (Estimated): June 28, 2027

Study Registration Dates

• First Submitted: May 23, 2022
• First Submitted That Met QC Criteria: May 23, 2022
• First Posted (Actual): May 26, 2022

Study Record Updates

• Last Update Posted (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: oligodendroglioma; astrocytoma; IDH mutant glioma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma; Astrocytoma; Oligodendroglioma
• Other Study ID Numbers: 202205105

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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