Low Dose Radiation Therapy for Glioblastoma Multiforme

NCT01466686 | Completed Phase 2 Results DMC

• 2 other identifiers: J11120NA_00065863
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 3

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.

Conditions

High Grade Glioma

Keywords

Recurrent Glioblastoma Multiforme; Recurrent Anaplastic Astrocytoma; Surgery; Adjuvant Radiation; Adjuvant Temozolomide

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Progression Free Survival Rate

  up to 12 months after completion of temozolomide (48 weeks of treatment)

• Number of Patients With 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

  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

Study Arms (1)

Temozolomide with Low Dose Fractionated Radiation Therapy

EXPERIMENTAL

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); Drug: Temozolomide

Interventions

Low Dose Fractionated Radiation Therapy (LDFRT) RADIATION

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.

Temozolomide with Low Dose Fractionated Radiation Therapy

Temozolomide DRUG

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.

Temozolomide with Low Dose Fractionated Radiation Therapy

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead

Study Sites (3)

Sibley Memorial Hospital

Washington D.C., District of Columbia, 20016, United States

Location

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

Suburban Hospital

Bethesda, Maryland, 20814, United States

Location

MeSH Terms

Conditions

Glioma; Glioblastoma; Astrocytoma

Interventions

Temozolomide

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Kristin Redmond, MD
• Organization: Sidney Kimmel Comprehensive Cancer Center @ Johns Hopkins Medicine

kjanson3@jhmi.edu

4109556980

Study Officials

• Kristin Redmond, M.D.

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2011
• First Posted: November 8, 2011
• Study Start: September 1, 2012
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2022
• Last Updated: July 3, 2023
• Results First Posted: July 3, 2023

Record last verified: 2023-06

Locations

US (3)