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Mathematical Model-Adapted Radiation In Glioblastoma

Primary Purpose

Recurrent Glioblastoma

Status
Unknown status
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Mathematical Model-Adapted Radiation Fractionation Schedule
Sponsored by
Dana-Farber Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Glioblastoma focused on measuring Recurrent glioblastoma, Radiation Therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Participants must have recurrent glioblastoma (WHO Grade IV), as defined on brain imaging with CT or MRI, after prior receipt of definitive therapy including neurosurgical biopsy or resection and radiation therapy with or without systemic therapy.
  • Participants must be deemed appropriate candidates for re-irradiation
  • Histopathologic confirmation of disease as part of routine clinical care is required either at the time of initial diagnosis and/or at the time of recurrent disease. There is no requirement for central pathologic review.
  • Age ≥ 18 years at the time of enrollment
  • Karnofsky Performance Status (KPS) of at least 70
  • Exclusion Criteria
  • Participants who have received more than one prior course of radiotherapy to the local site of progressive disease
  • Participants who have received prior radiotherapy to the local site of progressive disease within < 3 months of the anticipated start of re-irradiation
  • Participants with recurrent tumor extensively abutting or involving the optic structures or brainstem, as assessed by the treating radiation oncologist
  • Participants without a definable tumor cavity on MRI or CT obtained at study enrollment
  • Participants receiving concurrent cytotoxic chemotherapy (i.e. temozolomide, CCNU, vincristine, procarbazine) or concurrent immunotherapy (i.e. pembrolizumab, nivolumab); however, participants may receive sequential chemotherapy before or after radiation without limitation. Participants may receive concurrent corticosteroid and/or anti-angiogenic therapy (i.e. bevacizumab) if clinically indicated.

Sites / Locations

  • Brigham and Women's Hospital
  • Dana-Farber Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Mathematical Model-Adapted Radiation

Arm Description

Mathematical Model-Adapted Radiation Fractionation Schedule

Outcomes

Primary Outcome Measures

Number of Participants to Complete Model Adapted Radiations Fractionation Scheduled
Feasibility is defined as successful completion of radiation therapy for at least 13 of 14 patients. Successful completion of radiotherapy is defined as receipt of all scheduled fractions of daily radiotherapy within 24 hours of once daily fractions and within 1 hour of three-times daily fractions.

Secondary Outcome Measures

Quality of Life (MD Anderson Symptom Inventory Brain Tumor)
MDASI-BT index. 22 questions about different symptoms rated on a scale from 1 to 10, 1 being "not present" and 10 being "as bad as you can imagine," plus 5 questions about the impact of symptoms on quality of life on a scale from 1 to 10, 1 being "doesn't interfere" and 10 being "completely interferes." Subscales are not combined.
Quality of Life (MD Anderson Symptom Inventory Brain Tumor)
MDASI-BT index. 22 questions about different symptoms rated on a scale from 1 to 10, 1 being "not present" and 10 being "as bad as you can imagine," plus 5 questions about the impact of symptoms on quality of life on a scale from 1 to 10, 1 being "doesn't interfere" and 10 being "completely interferes." Subscales are not combined.
Incidence of Radiation Necrosis
Kaplan-Meier plot, Cox regression
Time to Development of Radiation Necrosis
Kaplan-Meier plot, Cox regression
Incidence of Seizures
Kaplan-Meier plot, Cox regression
Time to the Development of Seizures
Kaplan-Meier plot, Cox regression
Overall Survival
Kaplan-Meier plot, Cox regression
Karnofsky Performance Status
Longitudinal regression
Incidence of Grade 3+ Acute or Delayed CNS Toxicity
CTCAEv5.0; Exact binomial distribution with 95% confidence intervals
Time to the Development of Grade 3+ Acute or Delayed CNS Toxicity
CTCAEv5.0
Progression-free Survival
Kaplan-Meier plot, Cox regression
Local Recurrence
Kaplan-Meier plot
Incidence of Salvage Craniotomy
Kaplan-Meier plot, Cox regression
Time to Salvage Craniotomy
Kaplan-Meier plot, Cox regression
Incidence of Additional Systemic Treatments After Reirradiation
Kaplan-Meier plot, Cox regression
Time to Additional Systemic Treatments After Reirradiation
Kaplan-Meier plot, Cox regression
Tumor Volumes
Based on the intended radiation administration times and actual radiation administration times) will be compared to the measured tumor volumes obtained from the MRI data that will be collected for the RANO response criteria using residual sum of squares

Full Information

First Posted
May 23, 2018
Last Updated
June 15, 2021
Sponsor
Dana-Farber Cancer Institute
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1. Study Identification

Unique Protocol Identification Number
NCT03557372
Brief Title
Mathematical Model-Adapted Radiation In Glioblastoma
Official Title
Mathematical Model-Adapted Radiation Fractionation Schedule for Patients With Recurrent Glioblastoma (MARS-Glio)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Unknown status
Study Start Date
November 12, 2018 (Actual)
Primary Completion Date
June 1, 2020 (Actual)
Study Completion Date
June 1, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dana-Farber Cancer Institute

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.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This research study is studying a new schedule of radiation therapy for recurrent glioblastoma as a possible treatment for this diagnosis. This radiation schedule is based on a new model for radiation resistance in glioblastoma. The name of the radiation schedule involved in this study is: - Re-irradiation for glioblastoma using a novel Mathematical Model-Adapted Radiation Fractionation Schedule
Detailed Description
This research study is a Feasibility Study, which means that this is the first time that investigators are examining this new radiation schedule for recurrent glioblastoma. The FDA (the U.S. Food and Drug Administration) has approved radiation therapy as a treatment option for your disease. This is the first time that this particular radiation schedule will be tested in humans. There many other studies which have tested different radiation schedules in glioblastoma. In this research study, investigators are adapting a standard two-week schedule of radiation commonly used for recurrent glioblastoma using a mathematical model. This study uses the same total dose of radiation as standard treatments but breaks up the dose into different amounts daily to maximize tumor kill. investigators have used a new mathematical model to create this schedule of radiation. This model was created to better represent how glioblastoma cells can escape the damaging effects of radiation. Based on the results of several laboratory studies, it is possible that this model may result in improved outcomes compared to standard radiation schedules. The primary question of this study is to see whether participants can complete this new radiation schedule at the scheduled times. In addition, investigators will follow participants to ensure that this treatment is safe. If this treatment proves feasible, investigators hope to compare this treatment directly with standard radiation schedules for newly diagnosed and recurrent glioblastoma.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Glioblastoma
Keywords
Recurrent glioblastoma, Radiation Therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Mathematical Model-Adapted Radiation
Arm Type
Experimental
Arm Description
Mathematical Model-Adapted Radiation Fractionation Schedule
Intervention Type
Radiation
Intervention Name(s)
Mathematical Model-Adapted Radiation Fractionation Schedule
Intervention Description
Re-irradiation with 35 Gy delivered over 2 weeks, based upon reference dosing of 35 Gy in 10 Fractions over 2 weeks Radiation therapy is delivered on Monday-Friday during standard clinic hours in our department. Each treatment may take 20-40 minutes. Treatment will be once daily for the first 7 days of treatment and then three-times daily for the last three days of treatment.
Primary Outcome Measure Information:
Title
Number of Participants to Complete Model Adapted Radiations Fractionation Scheduled
Description
Feasibility is defined as successful completion of radiation therapy for at least 13 of 14 patients. Successful completion of radiotherapy is defined as receipt of all scheduled fractions of daily radiotherapy within 24 hours of once daily fractions and within 1 hour of three-times daily fractions.
Time Frame
10 Days
Secondary Outcome Measure Information:
Title
Quality of Life (MD Anderson Symptom Inventory Brain Tumor)
Description
MDASI-BT index. 22 questions about different symptoms rated on a scale from 1 to 10, 1 being "not present" and 10 being "as bad as you can imagine," plus 5 questions about the impact of symptoms on quality of life on a scale from 1 to 10, 1 being "doesn't interfere" and 10 being "completely interferes." Subscales are not combined.
Time Frame
Baseline and 4 weeks after Completion of Reirradiation
Title
Quality of Life (MD Anderson Symptom Inventory Brain Tumor)
Description
MDASI-BT index. 22 questions about different symptoms rated on a scale from 1 to 10, 1 being "not present" and 10 being "as bad as you can imagine," plus 5 questions about the impact of symptoms on quality of life on a scale from 1 to 10, 1 being "doesn't interfere" and 10 being "completely interferes." Subscales are not combined.
Time Frame
6 months
Title
Incidence of Radiation Necrosis
Description
Kaplan-Meier plot, Cox regression
Time Frame
6 months
Title
Time to Development of Radiation Necrosis
Description
Kaplan-Meier plot, Cox regression
Time Frame
6 months
Title
Incidence of Seizures
Description
Kaplan-Meier plot, Cox regression
Time Frame
6 months
Title
Time to the Development of Seizures
Description
Kaplan-Meier plot, Cox regression
Time Frame
6 months
Title
Overall Survival
Description
Kaplan-Meier plot, Cox regression
Time Frame
6 months
Title
Karnofsky Performance Status
Description
Longitudinal regression
Time Frame
6 months
Title
Incidence of Grade 3+ Acute or Delayed CNS Toxicity
Description
CTCAEv5.0; Exact binomial distribution with 95% confidence intervals
Time Frame
6 Months
Title
Time to the Development of Grade 3+ Acute or Delayed CNS Toxicity
Description
CTCAEv5.0
Time Frame
6 Months
Title
Progression-free Survival
Description
Kaplan-Meier plot, Cox regression
Time Frame
6 Months
Title
Local Recurrence
Description
Kaplan-Meier plot
Time Frame
6 Months
Title
Incidence of Salvage Craniotomy
Description
Kaplan-Meier plot, Cox regression
Time Frame
6 Months
Title
Time to Salvage Craniotomy
Description
Kaplan-Meier plot, Cox regression
Time Frame
6 Months
Title
Incidence of Additional Systemic Treatments After Reirradiation
Description
Kaplan-Meier plot, Cox regression
Time Frame
6 Months
Title
Time to Additional Systemic Treatments After Reirradiation
Description
Kaplan-Meier plot, Cox regression
Time Frame
6 Months
Title
Tumor Volumes
Description
Based on the intended radiation administration times and actual radiation administration times) will be compared to the measured tumor volumes obtained from the MRI data that will be collected for the RANO response criteria using residual sum of squares
Time Frame
6 Months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participants must have recurrent glioblastoma (WHO Grade IV), as defined on brain imaging with CT or MRI, after prior receipt of definitive therapy including neurosurgical biopsy or resection and radiation therapy with or without systemic therapy. Participants must be deemed appropriate candidates for re-irradiation Histopathologic confirmation of disease as part of routine clinical care is required either at the time of initial diagnosis and/or at the time of recurrent disease. There is no requirement for central pathologic review. Age ≥ 18 years at the time of enrollment Karnofsky Performance Status (KPS) of at least 70 Exclusion Criteria Participants who have received more than one prior course of radiotherapy to the local site of progressive disease Participants who have received prior radiotherapy to the local site of progressive disease within < 3 months of the anticipated start of re-irradiation Participants with recurrent tumor extensively abutting or involving the optic structures or brainstem, as assessed by the treating radiation oncologist Participants without a definable tumor cavity on MRI or CT obtained at study enrollment Participants receiving concurrent cytotoxic chemotherapy (i.e. temozolomide, CCNU, vincristine, procarbazine) or concurrent immunotherapy (i.e. pembrolizumab, nivolumab); however, participants may receive sequential chemotherapy before or after radiation without limitation. Participants may receive concurrent corticosteroid and/or anti-angiogenic therapy (i.e. bevacizumab) if clinically indicated.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shyam Tanguturi, MD
Organizational Affiliation
Brigham and Women's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States

12. IPD Sharing Statement

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Mathematical Model-Adapted Radiation In Glioblastoma

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