Low Dose Radiation Therapy for Glioblastoma Multiforme

This study is currently recruiting participants.
Verified November 2012 by Sidney Kimmel Comprehensive Cancer Center
Sponsor:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01466686
First received: November 3, 2011
Last updated: November 15, 2012
Last verified: November 2012
  Purpose

To evaluate the safety and effectiveness of low dose rate radiation therapy plus temozolomide. This will be in patients with recurrent glioblastoma Multiforme who have previously been treated with surgery followed by radiation surgical resection followed by adjuvant radiation therapy plus temozolomide.


Condition Intervention Phase
Glioblastoma Multiforme
Radiation: Low Dose Fractionated Radiation Therapy (LDFRT)
Drug: Temozolomide
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Low Dose Fractionated Radiation Therapy as a Chemo-progenitor of Salvage Temozolomide for Recurrent Glioblastoma Multiforme

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • Safety [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    To select a safe tolerated dose schedule (ie: number of consecutive twice daily fractions) of LDFRT + temozolomide based on hematologic toxicity at one month following initiation of therapy.

  • Tolerability [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    To select a tolerated dose schedule (ie: number of consecutive twice daily fractions) of LDFRT + temozolomide based on hematologic toxicity at one month following initiation of therapy.


Secondary Outcome Measures:
  • Radiation Toxicity [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    To estimate the acute and late radiation-associated neurologic toxicity of salvage LDFRT + temozolomide.


Estimated Enrollment: 49
Study Start Date: September 2012
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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. 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.
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.

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 recurrent GBM 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have recurrent GBM.
  • The diagnosis of GBM
  • At the time of initial diagnosis, patients must have been treated with surgical resection followed by adjuvant radiation therapy plus temozolomide
  • Patients must be at least 12 months from completion of radiation therapy
  • At least 9 months from completion of adjuvant temozolomide.
  • 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01466686

Contacts
Contact: Kristin Redmond, M.D. 410-614-1642 kjanson3@jhmi.edu
Contact: Kelly Szajna, R.N. 410-614-3950 kszajna1@jhmi.edu

Locations
United States, Maryland
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21231
Principal Investigator: Kristin Redmond, M.D.            
Sub-Investigator: Eric Ford, Ph.D.            
Sub-Investigator: Stuart Grossman, M.D.            
Sub-Investigator: Matthias Holdhoff, M.D.            
Sub-Investigator: John Lattera, M.D.            
Sub-Investigator: Jaishri Blakeley, M.D.            
Sub-Investigator: Xiaobu Ye, M.D.            
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Principal Investigator: Kristin Redmond, M.D. Johns Hopkins University
  More Information

No publications provided

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01466686     History of Changes
Other Study ID Numbers: J-11120, NA_00065863
Study First Received: November 3, 2011
Last Updated: November 15, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
Recurrent Glioblastoma Multiforme
Surgery
Adjuvant Radiation
Adjuvant Temozolomide

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 23, 2013