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Low Dose Radiation Therapy for Glioblastoma Multiforme

Primary Purpose

High Grade Glioma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Low Dose Fractionated Radiation Therapy (LDFRT)
Temozolomide
Sponsored by
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for High Grade Glioma focused on measuring Recurrent Glioblastoma Multiforme, Recurrent Anaplastic Astrocytoma, Surgery, Adjuvant Radiation, Adjuvant Temozolomide

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients must have recurrent GBM (Glioblastoma Multiforme)or Anaplastic Astrocytoma.
  • The diagnosis of GBM or Anaplastic Astrocytoma.
  • Patients must have been previously treated with surgical resection (any extent okay) and adjuvant radiation therapy plus temozolomide.
  • Patients must be at least 12 months from completion of radiation therapy
  • At least 2 months from completion of temozolomide (to be consistent with the the "rechallenge" group from Perry et al. JCO 2010).
  • Age >18 years
  • ECOG performance status <2 (Karnofsky >60%, see appendix A).
  • There must be measurable disease on MRI.
  • Patients must have normal organ and marrow function as defined below:
  • Women must not be pregnant
  • Ability to understand and the willingness to sign a written informed consent document
  • Temozolomide re-treatment is planned by the treating neuro-oncologist.
  • The most recent brain tumor pathology obtained for the patient must be glioblastoma.

Exclusion Criteria:

  • Must be able to receive an MRI
  • Patients may not be receiving any other investigational cancer treatment agents at the time of enrollment.
  • Patients may not have previously failed treatment with salvage temozolomide.
  • Patients may not have previously failed treatment with a VEGF inhibitor.
  • Patients may not have previously been treated with >1 course of radiotherapy.
  • Patients may not have previously been treated with radiosurgery to the brain.
  • Uncontrolled intercurrent illness
  • Pregnant and breastfeeding women are excluded. Women of child-bearing potential who are unwilling or unable to use and acceptable method of birth control to avoid pregnancy for the entire study period and up to 12 weeks after the study are excluded. Male subjects must also agree to use effective contraception for the same period as above.

Sites / Locations

  • Sibley Memorial Hospital
  • The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Suburban Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Temozolomide with Low Dose Fractionated Radiation Therapy

Arm Description

All patients will receive temozolomide (150 to 200 mg per square meter for 5 days during each 28 day cycle) for a total of 1 year or until the time of disease progression. All patients will receive 0.5 Gy of radiation therapy twice daily. This study will include a safety run-in component. If > 33% of patients in the initial cohort of 6 experience grade 3 or greater hematologic toxicity according to the NCI Common Toxicity Criteria version 4, then a dose reduction will occur following the schedule listed below. Otherwise, following a 1 month waiting period after the first cycle of adjuvant LDFRT plus temozolomide for the first cohort of patients, the phase 2 study will open for full accrual. Patients will receive radiation with the first six 28-day cycles of temozolomide.

Outcomes

Primary Outcome Measures

Response Rate
To estimate the response rate to salvage temozolomide plus LDFRT.
Overall Survival Rate
Overall survival rate is calculated as the median number of months that patients were alive for the cohort

Secondary Outcome Measures

Progression Free Survival Rate
Progression free survival rate is calculated as the median number of months for the cohort until patient's disease worsened/progressed
Number of Patients With Hematologic Toxicities
The number of patients with grade 3+ hematologic toxicities.
Number of Patients With Neurologic Toxicity
The number of patients with reported grade 3+ neurologic toxicities

Full Information

First Posted
November 3, 2011
Last Updated
June 14, 2023
Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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1. Study Identification

Unique Protocol Identification Number
NCT01466686
Brief Title
Low Dose Radiation Therapy for Glioblastoma Multiforme
Official Title
A Phase II Trial of Low Dose Fractionated Radiation Therapy as a Chemo-Potentiator of Salvage Temozolomide for Recurrent Anaplastic Astrocytoma and Glioblastoma Multiforme
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
September 2012 (Actual)
Primary Completion Date
December 2021 (Actual)
Study Completion Date
December 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
To evaluate the safety and effectiveness of low dose rate radiation therapy plus temozolomide. This will be in patients with High Grade Glioma (to only include Anaplastic Astrocytoma or Glioblastoma Multiforme) who have previously been treated with surgery followed by radiation surgical resection followed by adjuvant radiation therapy plus temozolomide.
Detailed Description
In vitro and in vivo studies have suggested that low dose fractionated radiation therapy (LDFRT) may be used to potentiate full dose chemotherapy, decreasing the development of resistance found with standard doses of radiation and chemotherapy. This is a nonrandomized, open label, single institution phase II trial with a safety run-in to evaluate the safety and efficacy of LDFRT plus temozolomide in patients with High Grade Glioma (to only include Anaplastic Astrocytoma or Glioblastoma Multiforme) previously treated with surgical resection followed by adjuvant radiation therapy plus temozolomide. The primary objective of the phase II study is to estimate response rate in patients treated with twice daily fractions of low dose radiation plus temozolomide chemotherapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
High Grade Glioma
Keywords
Recurrent Glioblastoma Multiforme, Recurrent Anaplastic Astrocytoma, Surgery, Adjuvant Radiation, Adjuvant Temozolomide

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
31 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Temozolomide with Low Dose Fractionated Radiation Therapy
Arm Type
Experimental
Arm Description
All patients will receive temozolomide (150 to 200 mg per square meter for 5 days during each 28 day cycle) for a total of 1 year or until the time of disease progression. All patients will receive 0.5 Gy of radiation therapy twice daily. This study will include a safety run-in component. If > 33% of patients in the initial cohort of 6 experience grade 3 or greater hematologic toxicity according to the NCI Common Toxicity Criteria version 4, then a dose reduction will occur following the schedule listed below. Otherwise, following a 1 month waiting period after the first cycle of adjuvant LDFRT plus temozolomide for the first cohort of patients, the phase 2 study will open for full accrual. Patients will receive radiation with the first six 28-day cycles of temozolomide.
Intervention Type
Radiation
Intervention Name(s)
Low Dose Fractionated Radiation Therapy (LDFRT)
Intervention Description
All patients will receive 0.5 Gy of radiation therapy twice daily. This study will include a safety run-in component. If > 33% of patients in the initial cohort of 6 experience grade 3 or greater hematologic toxicity according to the NCI Common Toxicity Criteria version 4, then a dose reduction will occur following the schedule listed below.
Intervention Type
Drug
Intervention Name(s)
Temozolomide
Intervention Description
All patients will receive temozolomide (150 to 200 mg per square meter for 5 days during each 28 day cycle) for a total of 1 year or until the time of disease progression.
Primary Outcome Measure Information:
Title
Response Rate
Description
To estimate the response rate to salvage temozolomide plus LDFRT.
Time Frame
3, 6 and 12 month follow-up after therapy has been completed
Title
Overall Survival Rate
Description
Overall survival rate is calculated as the median number of months that patients were alive for the cohort
Time Frame
up to 12 months after completion of temozolomide (48 weeks of treatment)
Secondary Outcome Measure Information:
Title
Progression Free Survival Rate
Description
Progression free survival rate is calculated as the median number of months for the cohort until patient's disease worsened/progressed
Time Frame
up to 12 months after completion of temozolomide (48 weeks of treatment)
Title
Number of Patients With Hematologic Toxicities
Description
The number of patients with grade 3+ hematologic toxicities.
Time Frame
Approximately every month from study start until 48 weeks, and then up to 12 months after completion of temozolomide at 3, 6, and 12 months follow up
Title
Number of Patients With Neurologic Toxicity
Description
The number of patients with reported grade 3+ neurologic toxicities
Time Frame
Approximately every month from study start until 48 weeks, and then up to 12 months after completion of temozolomide at 3, 6, and 12 months follow up

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have recurrent GBM (Glioblastoma Multiforme)or Anaplastic Astrocytoma. The diagnosis of GBM or Anaplastic Astrocytoma. Patients must have been previously treated with surgical resection (any extent okay) and adjuvant radiation therapy plus temozolomide. Patients must be at least 12 months from completion of radiation therapy At least 2 months from completion of temozolomide (to be consistent with the the "rechallenge" group from Perry et al. JCO 2010). Age >18 years ECOG performance status <2 (Karnofsky >60%, see appendix A). There must be measurable disease on MRI. Patients must have normal organ and marrow function as defined below: Women must not be pregnant Ability to understand and the willingness to sign a written informed consent document Temozolomide re-treatment is planned by the treating neuro-oncologist. The most recent brain tumor pathology obtained for the patient must be glioblastoma. Exclusion Criteria: Must be able to receive an MRI Patients may not be receiving any other investigational cancer treatment agents at the time of enrollment. Patients may not have previously failed treatment with salvage temozolomide. Patients may not have previously failed treatment with a VEGF inhibitor. Patients may not have previously been treated with >1 course of radiotherapy. Patients may not have previously been treated with radiosurgery to the brain. Uncontrolled intercurrent illness Pregnant and breastfeeding women are excluded. Women of child-bearing potential who are unwilling or unable to use and acceptable method of birth control to avoid pregnancy for the entire study period and up to 12 weeks after the study are excluded. Male subjects must also agree to use effective contraception for the same period as above.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kristin Redmond, M.D.
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sibley Memorial Hospital
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20016
Country
United States
Facility Name
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
Facility Name
Suburban Hospital
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20814
Country
United States

12. IPD Sharing Statement

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Low Dose Radiation Therapy for Glioblastoma Multiforme

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