Radiation Therapy with or without Temozolomide in Treating Patients with Anaplastic Glioma

Status: Closed to Accrual

Description

This randomized phase III trial studies temozolomide given during and / or after radiation therapy to see how well it works compared to radiation therapy alone in treating patients with anaplastic glioma. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving radiation therapy together with temozolomide may kill more tumor cells. It is not yet known whether giving temozolomide during and / or after radiation therapy is more effective than radiation therapy alone in treating anaplastic glioma.

Eligibility Criteria

Inclusion Criteria

  • Histologically confirmed diagnosis of 1 of the following: * Anaplastic oligodendroglioma * Anaplastic oligoastrocytoma * Anaplastic astrocytoma
  • Newly diagnosed disease
  • Prior surgery for a low grade tumor is allowed, provided histological confirmation of anaplastic tumor is present at the time of progression
  • Absence of combined 1p/19q loss
  • Tumor material available for central 1p/19q assessment, central O6-methylguanine-deoxyribonucleic acid (DNA) methyltransferase promoter methylation status assessment, isocitrate dehydrogenase mutation analysis, and central pathology review
  • Patients must be on a stable or decreasing dose of steroids for at least two weeks prior to randomization
  • World Health Organization (WHO) performance status 0-2
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9 cells/L
  • Platelet count >= 100 x 10^9 cells/L
  • Bilirubin < 1.5 x upper limit of normal (ULN)
  • Alkaline phosphatase < 2.5 x ULN
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x ULN
  • Serum creatinine < 1.5 x ULN
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No known human immunodeficiency virus (HIV) infection or chronic hepatitis B or hepatitis C infection
  • No other serious medical condition that would interfere with follow-up
  • No medical condition that could interfere with oral medication intake (e.g., frequent vomiting or partial bowel obstruction)
  • No prior or concurrent malignancies at other sites except for surgically cured carcinoma in situ of the cervix or nonmelanoma skin cancer
  • No psychological, familial, sociological, or geographical condition that would potentially hamper compliance with the study protocol and follow-up schedule
  • No prior chemotherapy, including carmustine-containing wafers (Gliadel®)
  • No prior radiotherapy to the brain
  • No concurrent growth factors unless vital for the patient
  • No other concurrent investigational treatment
  • No other concurrent anticancer agents

Locations & Contacts

See trial information on ClinicalTrials.gov for a list of participating sites.

Trial Objectives and Outline

PRIMARY OBJECTIVES:

l. To assess whether concurrent radiotherapy with daily temozolomide improves overall survival as compared to no daily temozolomide in patients with non-1p/19q deleted anaplastic glioma.

II. To assess whether adjuvant temozolomide improves survival as compared to no adjuvant temozolomide in patients with non-1p/19q deleted anaplastic glioma.

SECONDARY OBJECTIVES:

I. To assess whether concurrent and adjuvant temozolomide prolongs progression-free survival and neurological deterioration-free survival in patients with non-1p/19q deleted anaplastic glioma.

II. To assess the safety of concurrent and adjuvant temozolomide in patients with non-1p/19q deleted anaplastic glioma, including late effects on cognition.

III. To assess the impact of concurrent and adjuvant temozolomide on the quality of life of patients with non-1p/19q deleted anaplastic glioma.

OUTLINE: Patients are randomized to 1 of 4 treatment arms.

ARM I: Patients undergo radiation therapy once daily (QD) 5 days a week, for 6.5 weeks (total of 33 fractions).

ARM II: Patients undergo radiation therapy as in Arm I and receive temozolomide orally (PO) QD for 6.5 weeks (total of 33 fractions of radiation therapy).

ARM III: Patients undergo radiation therapy as in Arm I. Beginning 4 weeks after completion of radiotherapy, patients receive adjuvant temozolomide PO QD on days 1-5. Treatment with adjuvant temozolomide repeats every 28 days for up to 12 courses.

ARM IV: Patients undergo radiation therapy and temozolomide PO as in Arm I. Beginning 4 weeks after completion of radiation therapy, patients receive adjuvant temozolomide as in Arm III.

In all arms, treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

Trial Phase & Type

Trial Phase

Phase III

Trial Type

Treatment

Lead Organization

Lead Organization
NRG Oncology

Principal Investigator
Michael A. Vogelbaum

Trial IDs

Primary ID RTOG-0834
Secondary IDs NCI-2011-02070, MERCK-EORTC-26053, EORTC-22054, EORTC-26053, EUDRACT-2006-001533-17, COGNO-EORTC-26053, MRC-BR14, CDR0000582632, CAN-NCIC-CEC1
Clinicaltrials.gov ID NCT00626990