Low Dose Radiation Therapy for Glioblastoma Multiforme

High Grade Glioma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01466686
• Other study ID #: J11120
• Secondary ID: NA_00065863
• Status: Completed
• Phase: Phase 2
• Start date: September 2012
• Est. completion date: December 2022

Study information

• Verified date: June 2023
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: December 2022
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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.

Related Conditions & MeSH terms

• Glioblastoma
• High Grade Glioma

Intervention

Radiation:
• Low Dose Fractionated Radiation Therapy (LDFRT)
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.

Drug:
• Temozolomide
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.

Locations

Country	Name	City	State
United States	The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Suburban Hospital	Bethesda	Maryland
United States	Sibley Memorial Hospital	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response Rate	To estimate the response rate to salvage temozolomide plus LDFRT.	3, 6 and 12 month follow-up after therapy has been completed
Primary	Overall Survival Rate	Overall survival rate is calculated as the median number of months that patients were alive for the cohort	up to 12 months after completion of temozolomide (48 weeks of treatment)
Secondary	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	up to 12 months after completion of temozolomide (48 weeks of treatment)
Secondary	Number of Patients With Hematologic Toxicities	The number of patients with grade 3+ hematologic toxicities.	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
Secondary	Number of Patients With Neurologic Toxicity	The number of patients with reported grade 3+ neurologic toxicities	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