Low Dose Radiation Therapy for Glioblastoma Multiforme

A Phase II Trial of Low Dose Fractionated Radiation Therapy as a Chemo-Potentiator of Salvage Temozolomide for Recurrent Anaplastic Astrocytoma and Glioblastoma Multiforme

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.

Study Overview

• Status: Completed
• Conditions: High Grade Glioma
• Intervention / Treatment: Radiation: Low Dose Fractionated Radiation Therapy (LDFRT); Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20016
      • Sibley Memorial Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • Bethesda, Maryland, United States, 20814
      • Suburban Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

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: Temozolomide with Low Dose Fractionated Radiation Therapy; 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.

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate	To estimate the response rate to salvage temozolomide plus LDFRT.	3, 6 and 12 month follow-up after therapy has been completed
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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
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

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Investigators: Principal Investigator: Kristin Redmond, M.D., Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2012
• Primary Completion (Actual): December 1, 2021
• Study Completion (Actual): December 1, 2022

Study Registration Dates

• First Submitted: November 3, 2011
• First Submitted That Met QC Criteria: November 7, 2011
• First Posted (Estimated): November 8, 2011

Study Record Updates

• Last Update Posted (Actual): July 3, 2023
• Last Update Submitted That Met QC Criteria: June 14, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Surgery; Recurrent Glioblastoma Multiforme; Recurrent Anaplastic Astrocytoma; Adjuvant Temozolomide; Adjuvant Radiation
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: J11120; NA_00065863 (Other Identifier: Johns Hopkins University School of Medicine)