Back to resultsTemporally-modulated Pulsed Radiation Therapy (TMPRT) After Prior EBRT for Recurrent IDH-mutant Gliomas
Primary Purpose
Astrocytoma, Oligodendroglioma, Adult, Glioma, Malignant
Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
temporally-modulated pulsed radiotherapy (TMPRT)
Sponsored by
About this trial
This is an interventional treatment trial for Astrocytoma focused on measuring IDH mutant glioma, astrocytoma, oligodendroglioma
Eligibility Criteria
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 lesion size or any number of prior recurrences are allowed.
- 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.
Sites / Locations
- Washington University School of MedicineRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Arm 1: temporally-modulated pulsed radiotherapy (TMPRT)
Arm Description
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.
Outcomes
Primary Outcome Measures
Frequency of 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.
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
Secondary Outcome Measures
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.
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.
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).
Progression-free survival (PFS)
PFS is defined as the time from enrollment in the trial 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).
Overall survival (OS)
OS is defined as the time from enrollment in the trial until the date of death due to any cause.
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.
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.
Full Information
NCT ID
NCT05393258
First Posted
May 23, 2022
Last Updated
January 19, 2023
Sponsor
Washington University School of Medicine
1. Study Identification
Unique Protocol Identification Number
NCT05393258
Brief Title
Temporally-modulated Pulsed Radiation Therapy (TMPRT) After Prior EBRT for Recurrent IDH-mutant Gliomas
Official Title
A Pilot Study of Temporally-modulated Pulsed Radiation Therapy to Reirradiate Recurrent IDH-mutant Gliomas After Prior External Beam Radiation Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 28, 2022 (Actual)
Primary Completion Date
June 28, 2027 (Anticipated)
Study Completion Date
June 28, 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Astrocytoma, Oligodendroglioma, Adult, Glioma, Malignant
Keywords
IDH mutant glioma, astrocytoma, oligodendroglioma
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Arm 1: temporally-modulated pulsed radiotherapy (TMPRT)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Radiation
Intervention Name(s)
temporally-modulated pulsed radiotherapy (TMPRT)
Other Intervention Name(s)
pulsed low-dose-rate RT (PLRT), pulsed reduced-dose-rate RT (PRRT)
Intervention Description
Intensity modulated RT (IMRT) using single or two arc therapy will be used for RT delivery.
Primary Outcome Measure Information:
Title
Frequency of intolerable toxicities
Description
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.
Time Frame
From start of treatment through 3 months
Title
Cumulative incidence of grade 3 or higher reirradiation-related central nervous system adverse events
Description
Adverse events are graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
Time Frame
From start of treatment through 1 year
Secondary Outcome Measure Information:
Title
Change in symptom burden as measured by M.D. Anderson Symptom Inventory - Brain Tumor (MDASI-BT)
Description
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.
Time Frame
Assessed at approximately 3 months, 6 months, and 12 months after start of treatment
Title
Change in interference as measured by M.D. Anderson Symptom Inventory - Brain Tumor (MDASI-BT)
Description
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.
Time Frame
Assessed at approximately 3 months, 6 months, and 12 months after start of treatment
Title
Change in quality of life (QOL) as measured by self-reported QOL on the Linear Analog Scale Assessment (LASA)
Description
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).
Time Frame
Assessed at approximately 3 months, 6 months, and 12 months after start of treatment
Title
Progression-free survival (PFS)
Description
PFS is defined as the time from enrollment in the trial 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).
Time Frame
At one year after start of treatment
Title
Overall survival (OS)
Description
OS is defined as the time from enrollment in the trial until the date of death due to any cause.
Time Frame
At one year after start of treatment
Title
Relative changes of different subtypes of circulating T-cells
Description
Blood will be collected before the start of TMPRT and at week 6 of radiation therapy to assess for changes in circulating T-cells.
Time Frame
At baseline and week 6 of radiation therapy.
Title
Relative changes of different subtypes of myeloid cells
Description
Blood will be collected before the start of TMPRT and at week 6 of radiation therapy to assess for changes in myeloid cells.
Time Frame
At baseline and week 6 of radiation therapy.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 lesion size or any number of prior recurrences are allowed.
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jiayi Huang, M.D.
Phone
314-273-2931
Email
jiayi.huang@wustl.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jiayi Huang, M.D.
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jiayi Huang, M.D.
Phone
314-273-2931
Email
jiayi.huang@wustl.edu
First Name & Middle Initial & Last Name & Degree
Jiayi Huang, M.D.
First Name & Middle Initial & Last Name & Degree
Shahed Badiyan, M.D.
First Name & Middle Initial & Last Name & Degree
Stephanie Perkins, M.D.
First Name & Middle Initial & Last Name & Degree
Michael Prusator, Ph.D.
First Name & Middle Initial & Last Name & Degree
Milan Chheda, M.D.
First Name & Middle Initial & Last Name & Degree
Tanner Johanns, M.D., Ph.D.
First Name & Middle Initial & Last Name & Degree
George Ansstas, M.D.
First Name & Middle Initial & Last Name & Degree
Omar Butt, M.D., Ph.D.
First Name & Middle Initial & Last Name & Degree
Chris Abraham, M.D.
First Name & Middle Initial & Last Name & Degree
Yi Huang, M.S.
First Name & Middle Initial & Last Name & Degree
Dinesh Thotala, Ph.D.
First Name & Middle Initial & Last Name & Degree
Clifford Robinson, M.D.
First Name & Middle Initial & Last Name & Degree
Subhajit Ghosh, Ph.D.
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
http://www.siteman.wustl.edu
Description
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
Learn more about this trial
Temporally-modulated Pulsed Radiation Therapy (TMPRT) After Prior EBRT for Recurrent IDH-mutant Gliomas
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