Clinical Trial: Temozolomide and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme or Anaplastic Astrocytoma

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase I Trial of Hypofraction Radiotherapy + Temozolomide in the Treatment of Patients With Glioblastoma Multiforme and Anaplastic Astrocytoma of the Brain

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 Summary:

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.


Sponsor: Ohio State University Comprehensive Cancer Center

Current Primary Outcome: Maximum Tolerated Dose(MTD)of Temozolomide(TMZ) [ Time Frame: up to 12-16 months ]

This study is designed as a phase I dose escalation trial using the Standard Method of dose escalation of three patients per dose level to determine the MTD of TMZ (up to 75 mg/m 2 /day) when TMZ is used with HIMRT for patients with glioblastoma multiforme(GBM) or Anaplastic Astrocytoma(AA)of the brain. The 3 dose levels will be evaluated using the standard method to determine if either represents an MTD based on DLT. If DLT is not observed at all doses level, the greater of the three levels will be recommended for phase II evaluations of treatment effect.


Original Primary Outcome: Maximum tolerated dose of temozolomide

Current Secondary Outcome:

  • Time to Neuroradiological Evidence of Tumor Recurrence or Progression [ Time Frame: up to 12-16 months ]
    As a small phase I study, no inferential statistical tests of hypotheses are planned. Data collected will be providing descriptive summary statistics. However, these estimates will allow statistically sound experimental designs and sample size calculations for subsequent studies of therapeutic effect.
  • Survival Time [ Time Frame: up to 2 years ]
    All patients will be followed to death. Active follow-up with disease evaluation with scans will be terminated if the patient's physician deems it in the patient's interest not to continue or upon patient request.
  • Time Spent in a Karnofsky Performance Status of 60-100% [ Time Frame: up to 12-16 months ]
    Time spent in a KPS ≥70 was calculated from the date of diagnosis of Karonofsky Performance Status decline (KPS<70) or censored at the last date the patient was known with KPS ≥70. The KPS higher scores indicates normal activity status.


Original Secondary Outcome:

  • Time to Neuroradiological Evidence of Tumor Recurrence or Progression
  • Survival Time
  • Time Spent in a Karnofsky Performance Status of 60-100%


Information By: Ohio State University Comprehensive Cancer Center

Dates:
Date Received: February 10, 2009
Date Started: February 13, 2009
Date Completion:
Last Updated: February 22, 2017
Last Verified: February 2017