Clinical trial NCT00841555: Temozolomide and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme or Anaplastic Astrocytoma
Official title: A Phase I Trial of Hypofraction Radiotherapy + Temozolomide in the Treatment of Patients With Glioblastoma Multiforme and Anaplastic Astrocytoma of the Brain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Glioblastoma Multiforme/Anaplastic Astrocytoma
Keywords: adult giant cell glioblastoma
adult gliosarcoma
adult anaplastic astrocytoma
adult glioblastoma
GBM/AA
Lead sponsor: Ohio State University Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2009-02-11
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Giving chemotherapy together with radiation therapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of temozolomide when given together with radiation therapy in treating patients with newly diagnosed glioblastoma multiforme or anaplastic astrocytoma.

Detailed description: OBJECTIVES:

Primary

* To determine the maximum tolerated dose of temozolomide when given in combination with hypofractionated intensity-modulated conformal stereotactic radiotherapy in patients with newly diagnosed de novo glioblastoma multiforme or anaplastic astrocytoma.

Secondary

* To determine the time to neuroradiological evidence of tumor recurrence or progression in patients treated with this regimen.
* To determine the survival time of patients treated with this regimen.
* To determine the time spent in a Karnofsky performance status of 60-100%.

OUTLINE: This is a dose-escalation study of temozolomide.

Beginning 1-3 weeks following surgery or biopsy, patients receive oral temozolomide once daily for 5 weeks. Beginning 1 week after starting temozolomide, patients also undergo hypofractionated intensity-modulated conformal stereotactic radiotherapy once daily 5 days a week for 3 weeks.

After completion of study treatment, patients are followed at 1 month, 2 months, and 3 months, and then every 3 months thereafter.

Eligibility criteria: Inclusion Criteria:

* Patients who have De novo glioblastoma multiforme, anaplastic astrocytoma, anaplastic oligodendrogliomas, mixed anaplastic oligoastrocytomas, gliosarcoma of the Brain, not involving the brain stem or optics chiasm, diagnosed following biopsy or tumor removal.
* Age \> 18 years
* Given written consent
* Adequate bone marrow reserve(hemoglobin \> 10 grams, Absolute neutrophil count \> 1500 / mm3, platelets \> 100,000/ mm3)
* Normal renal function(BUN \< 24 mg/dL, Creatinine \< 1.3 mg/dL)
* Normal liver function(Total Bilirubin \< 1.5 mg/dL, SGPT/ALT \< 60 U/L)

Exclusion Criteria:

* Have a Karnofsky score of \< 60 \[Appendix B\] or age \< 18 years.
* Prior chemotherapy and/or radiotherapy of their glioblastomamultiforme, anaplastic astrocytoma, anaplastic oligodendrogliomas, mixed anaplastic oligoastrocytomas, gliosarcoma.
* Tumors located in the brainstem or optic chiasm.
* Prior radiation therapy to the brain
* Prior chemotherapy within the past 6 weeks.

Primary outcomes:
measure: Maximum Tolerated Dose(MTD)of Temozolomide(TMZ)
timeFrame: up to 12-16 months
Secondary outcomes:
measure: Time to Neuroradiological Evidence of Tumor Recurrence or Progression
timeFrame: up to 12-16 months
measure: Survival Time
timeFrame: up to 2 years
measure: Time Spent in a Karnofsky Performance Status of 60-100%
timeFrame: up to 12-16 months
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Ohio State University Comprehensive Cancer Center
name: Mario Ammirati, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ammirati M, Chotai S, Newton H, Lamki T, Wei L, Grecula J. Hypofractionated intensity modulated radiotherapy with temozolomide in newly diagnosed glioblastoma multiforme. J Clin Neurosci. 2014 Apr;21(4):633-7. doi: 10.1016/j.jocn.2013.09.005. Epub 2013 Oct 3.