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

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

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.

Study Overview

• Status: Completed
• Conditions: Glioblastoma Multiforme/Anaplastic Astrocytoma
• Intervention / Treatment: Drug: temozolomide; Radiation: Hypofractionated radiation therapy; Radiation: Intensity-modulated radiation therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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 Names: IMRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose(MTD)of Temozolomide(TMZ)	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.	up to 12-16 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Neuroradiological Evidence of Tumor Recurrence or Progression	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.	up to 12-16 months
Survival Time	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.	up to 2 years
Time Spent in a Karnofsky Performance Status of 60-100%	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.	up to 12-16 months

Collaborators and Investigators

• Sponsor: Ohio State University Comprehensive Cancer Center
• Investigators: Principal Investigator: Mario Ammirati, MD, Ohio State University Comprehensive Cancer Center

Publications and helpful links

General Publications

• 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.

Helpful Links

• Jamesline

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2009
• Primary Completion (Actual): February 13, 2013
• Study Completion (Actual): November 25, 2014

Study Registration Dates

• First Submitted: February 10, 2009
• First Submitted That Met QC Criteria: February 10, 2009
• First Posted (Estimate): February 11, 2009

Study Record Updates

• Last Update Posted (Actual): April 18, 2018
• Last Update Submitted That Met QC Criteria: April 16, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma; adult anaplastic astrocytoma; GBM/AA
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Astrocytoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: OSU-08119; NCI-2011-03149 (Registry Identifier: Clinical Trial Reporting Program (CTRP))