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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Mario Ammirati, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00841555
First received: February 10, 2009
Last updated: March 24, 2016
Last verified: March 2016
  Purpose

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.


Condition Intervention Phase
Glioblastoma Multiforme/Anaplastic Astrocytoma
Drug: temozolomide
Radiation: Hypofractionated radiation therapy
Radiation: Intensity-modulated radiation therapy
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial of Hypofraction Radiotherapy + Temozolomide in the Treatment of Patients With Glioblastoma Multiforme and Anaplastic Astrocytoma of the Brain

Resource links provided by NLM:


Further study details as provided by Ohio State University Comprehensive Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose(MTD)of Temozolomide(TMZ) [ Time Frame: up to 12-16 months ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Time to Neuroradiological Evidence of Tumor Recurrence or Progression [ Time Frame: up to 12-16 months ] [ Designated as safety issue: No ]
    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 time of death ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 9
Study Start Date: February 2009
Study Completion Date: November 2014
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hypofractionation Radiotherapy+Temozolomide
Patients will receive temozolomide PO daily for 5 weeks. Beginning week 1 after initiation of temozolomide therapy, patients undergo HIMRT times a week for a total of 15 fractions.
Drug: temozolomide

Chemotherapy will be given for 5 weeks; it will start 1 week before Radiotherapy, will continue for the 3 weeks of Radiotherapy, and will continue for 1 week post-Radiotherapy.

Dose Level 1: 50 mg/m2 x first 4 weeks/75 mg/m2 x last 1 weeks of treatment Dose Level 2: 65 mg/m2 x first 4 weeks/75 mg/m2 x last 1 weeks of treatment Dose Level 3: 75 mg/m2 over the entire 5 weeks of treatment

Other Names:
  • Temodar
  • Temodal
Radiation: Hypofractionated radiation therapy
Patients will undergo HIMRT
Radiation: Intensity-modulated radiation therapy
Patients undergo HIMRT
Other Name: IMRT

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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00841555

Locations
United States, Ohio
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Ohio State University Comprehensive Cancer Center
Investigators
Principal Investigator: Mario Ammirati, MD Ohio State University Comprehensive Cancer Center
  More Information

Additional Information:
Responsible Party: Mario Ammirati, Principal Investigator, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00841555     History of Changes
Other Study ID Numbers: OSU-08119  NCI-2011-03149 
Study First Received: February 10, 2009
Results First Received: March 24, 2016
Last Updated: March 24, 2016
Health Authority: United States: Institutional Review Board

Keywords provided by Ohio State University Comprehensive Cancer Center:
adult giant cell glioblastoma
adult gliosarcoma
adult anaplastic astrocytoma
adult glioblastoma
GBM/AA

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
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 30, 2016