Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Radiation Therapy Combined With Chemotherapy in Treating Patients With Anaplastic Astrocytoma or Mixed Gliomas

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Closed 18 and over NCI RTOG-9813 ECOG-R9813, NCCTG-RTOG-9813, RTOG-98-13, NCT00004259

Objectives

1. Compare the overall survival and time to tumor progression in patients with anaplastic astrocytoma or mixed gliomas treated with radiotherapy combined with temozolomide vs carmustine or lomustine vs temozolomide and carmustine (arm discontinued as of 8/15/02).
2. Compare the relative toxic effects of these regimens in these patients.
3. Correlate molecular analyses with overall survival and time to tumor progression in patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Histologically proven unifocal anaplastic astrocytoma or mixed gliomas, including the following:
  • Anaplastic oligoastrocytoma
  • Mixed oligodendroglial/astrocytic tumors
    • Oligodendroglial component must be no greater than 25%



• No vascular proliferation and necrosis



• Increased cellularity, pleomorphism, and nuclear atypia allowed



• No tumor predominantly located in the posterior fossa (i.e., brainstem or cerebellum)



• Patients with prior biopsy proven low grade astrocytoma who now have anaplastic astrocytoma and have had no prior radiotherapy or chemotherapy also eligible



• Study therapy must begin within 6 weeks of diagnosis



• No spinal cord tumors, spinal drop metastases, or metastases to noncontiguous meninges
  • Pathologic evidence of local meningeal infiltration by underlying tumor allowed

Prior/Concurrent Therapy:

Biologic therapy:

• No prior biologic therapy

Chemotherapy:

• See Disease Characteristics
• No prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• No prior radiotherapy to brain or head and neck

Surgery:

• Not specified

Other:

• No other concurrent anticancer treatment for anaplastic astrocytoma until a recurrence is detected

Patient Characteristics:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• At least 1 year

Hematopoietic:

• Hemoglobin at least 10 g/dL
• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 150,000/mm³

Hepatic:

• Bilirubin less than 2 times upper limit of normal (ULN)
• AST less than 2 times ULN
• Alkaline phosphatase less than 2 times ULN

Renal:

• Blood urea nitrogen no greater than 25 mg/dL
• Creatinine less than 1.5 times normal

Pulmonary:

• No pre-existing lung disease that, in the investigator's opinion, would preclude administration of carmustine or lomustine or completion of therapy

Other:

• No other major medical illness or psychiatric impairment that would preclude study compliance
• No other malignancy within the past 5 years except nonmelanomatous skin cancer or carcinoma in situ of the cervix
• No known hypersensitivity to 1 of the components of carmustine, lomustine, temozolomide, dacarbazine, or any other nitrosourea
• No active infection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

Expected Enrollment

A total of 30 patients will be accrued for phase I of the study and then a total of 454 patients (227 per treatment arm) will be accrued for phase III of the study within 4 years. (Phase I closed as of 8/15/02)

Outcomes

Overall survival (OS)
Time to tumor progression (TTP)
Toxicity
Correlation of molecular analyses with OS and TTP

Outline

This is a randomized, multicenter study. Patients are stratified according to age (under 50 vs 50 and over), Karnofsky performance status (60-80% vs 90-100%), and prior surgery (biopsy only vs resection).

Phase I (closed as of 8/15/02)

• Prior to initiating the randomization to 1 of 3 treatment arms in phase III, 15 patients are accrued to arm III. If 2 or more of the first 15 patients experience grade 3 or worse pulmonary toxicity OR if 5 or more of the first 15 patients experience grade 4-5 thrombocytopenia/neutropenia, then arm III treatment is discontinued.

Phase III

• Patients are randomized to 1 of 2 treatment arms.
  • Arm I: Patients undergo radiotherapy 5 days a week for 6 weeks. Patients receive oral temozolomide on days 1-5 of the first week of radiotherapy. Chemotherapy repeats every 4 weeks for a total of 12 courses.
  
  
  
  • Arm II: Patients undergo radiotherapy as in arm I. Patients receive carmustine IV or lomustine IV over 1-2 hours on days 1-3 of the first week of radiotherapy and a second course on days 56-58. Chemotherapy repeats every 8 weeks for a total of 6 courses.
  
  
  
  • Arm III (discontinued as of 8/15/02): Patients undergo radiotherapy as in arm I. Patients receive carmustine IV or lomustine IV over 3 hours on day 5 and oral temozolomide (2 hours after completion of carmustine or lomustine infusion) on days 1-5 of the first week of radiotherapy. Combination chemotherapy repeats every 8 weeks for 6 courses.
  
  
  

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

Chang SM, Seiferheld W, Curran W, et al.: Phase I study pilot arms of radiotherapy and carmustine with temozolomide for anaplastic astrocytoma (Radiation Therapy Oncology Group 9813): implications for studies testing initial treatment of brain tumors. Int J Radiat Oncol Biol Phys 59 (4): 1122-6, 2004.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Radiation Therapy Oncology Group

Susan Chang, MD, Protocol chair		Ph: 415-353-2966; 800-888-8664 Email: changs@neurosurg.ucsf.edu

North Central Cancer Treatment Group

Kurt Jaeckle, MD, Protocol chair		Ph: 904-953-7102

Eastern Cooperative Oncology Group

Peter Bushunow, MD, Protocol chair		Ph: 585-922-4020 Email: peter.bushunow@viahealth.org

Registry Information
Official Title		A Phase III Randomized Study (phase I closed) of Radiation Therapy and Temozolomide Versus Radiation Therapy and Nitrosourea for Anaplastic Astrocytoma And Mixed Anaplastic Oligoastrocytoma (Astrocytoma Dominant)
Trial Start Date		2000-06-16
Registered in ClinicalTrials.gov		NCT00004259
Date Submitted to PDQ		2000-01-04
Information Last Verified		2007-03-22
NCI Grant/Contract Number		CA21661

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