Clinical trial NCT01466686: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: High Grade Glioma
Keywords: Recurrent Glioblastoma Multiforme
Recurrent Anaplastic Astrocytoma
Surgery
Adjuvant Radiation
Adjuvant Temozolomide
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
First posted: 2011-11-08
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Response Rate
timeFrame: 3, 6 and 12 month follow-up after therapy has been completed
measure: Overall Survival Rate
timeFrame: up to 12 months after completion of temozolomide (48 weeks of treatment)
Secondary outcomes:
measure: Progression Free Survival Rate
timeFrame: up to 12 months after completion of temozolomide (48 weeks of treatment)
measure: Number of Patients With Hematologic Toxicities
timeFrame: 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
measure: Number of Patients With Neurologic Toxicity
timeFrame: 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
Other outcomes:
Locations:
city: Washington
country: United States
facility: Sibley Memorial Hospital
state: District of Columbia
city: Baltimore
country: United States
facility: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Bethesda
country: United States
facility: Suburban Hospital
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Kristin Redmond, M.D.
role: PRINCIPAL_INVESTIGATOR
References: