RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy, such as temozolomide and carmustine, use different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy with chemotherapy may kill more tumor cells.

PURPOSE: This randomized phase III trial is studying radiation therapy and temozolomide to see how well they work compared to radiation therapy and carmustine in treating patients with anaplastic astrocytoma or mixed gliomas.

Condition	Treatment or Intervention	Phase
adult anaplastic astrocytoma Mixed Gliomas	Drug: carmustine  Drug: temozolomide  Procedure: chemotherapy  Procedure: radiation therapy	Phase III

Further Study Details: 

OBJECTIVES:

• 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 vs temozolomide and carmustine (arm discontinued as of 8/15/02).
• Compare the relative toxic effects of these regimens in these patients.
• Correlate molecular analyses with overall survival and time to tumor progression in patients treated with these regimens.

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 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 over 3 hours on day 5 and oral temozolomide (2 hours after completion of carmustine 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.

PROJECTED ACCRUAL: 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)

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

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

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/mm^3
• Platelet count at least 150,000/mm^3

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 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 active infection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

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

Alabama
      MBCCOP - Gulf Coast, Mobile,  Alabama,  36607,  United States; Recruiting
      Mobile Infirmary Medical Center, Mobile,  Alabama,  36652-2144,  United States; Recruiting
Arizona
      CCOP - Mayo Clinic Scottsdale Oncology Program, Scottsdale,  Arizona,  85259-5404,  United States; Recruiting
      Foundation for Cancer Research and Education, Phoenix,  Arizona,  85013,  United States; Recruiting
California
      Enloe Cancer Center at Enloe Medical Center, Chico,  California,  95926,  United States; Recruiting
      UCSF Comprehensive Cancer Center, San Francisco,  California,  94115,  United States; Recruiting
      University of California Davis Cancer Center, Sacramento,  California,  95817,  United States; Recruiting
Colorado
      Poudre Valley Hospital, Fort Collins,  Colorado,  80524,  United States; Recruiting
      St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center, Grand Junction,  Colorado,  81502-1628,  United States; Recruiting
Florida
      Baptist Cancer Institute - Jacksonville, Jacksonville,  Florida,  32207,  United States; Recruiting
      Baptist-South Miami Regional Cancer Program, Miami,  Florida,  33176-2197,  United States; Recruiting
      CCOP - Mount Sinai Medical Center, Miami Beach,  Florida,  33140,  United States; Recruiting
      Mayo Clinic - Jacksonville, Jacksonville,  Florida,  32224,  United States; Recruiting
      University of Florida Shands Cancer Center, Gainesville,  Florida,  32610-0385,  United States; Recruiting
      University of Miami Sylvester Comprehensive Cancer Center, Miami,  Florida,  33136,  United States; Recruiting
Georgia
      CCOP - Atlanta Regional, Atlanta,  Georgia,  30342-1701,  United States; Recruiting
Hawaii
      MBCCOP - Hawaii, Honolulu,  Hawaii,  96813,  United States; Recruiting
Illinois
      CCOP - Carle Cancer Center, Urbana,  Illinois,  61801,  United States; Recruiting
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61615-7828,  United States; Recruiting
      Creticos Cancer Center at Advocate Illinois Masonic Medical Center, Chicago,  Illinois,  60657,  United States; Recruiting
      Good Shepherd Hospital, Barrington,  Illinois,  60010,  United States; Recruiting
      Hinsdale Hematology Oncology Associates, Hinsdale,  Illinois,  60521,  United States; Recruiting
      Ingalls Cancer Care Center at Ingalls Memorial Hospital, Harvey,  Illinois,  60426,  United States; Recruiting
      Lutheran General Cancer Care Center, Park Ridge,  Illinois,  60068,  United States; Recruiting
      Northwest Community Hospital, Arlington Heights,  Illinois,  60005,  United States; Recruiting
Indiana
      Indiana University Cancer Center, Indianapolis,  Indiana,  46202-5289,  United States; Recruiting
      Methodist Cancer Center at Methodist Hospital, Indianapolis,  Indiana,  46206-1367,  United States; Recruiting
Iowa
      CCOP - Cedar Rapids Oncology Project, Cedar Rapids,  Iowa,  52403-1206,  United States; Recruiting
      CCOP - Iowa Oncology Research Association, Des Moines,  Iowa,  50309-1016,  United States; Recruiting
      Cedar Rapids Oncology Associates, Cedar Rapids,  Iowa,  52403,  United States; Recruiting
      McFarland Clinic, P.C., Ames,  Iowa,  50010,  United States; Recruiting
      Mercy Cancer Center at Mercy Medical Center - Des Moines, Des Moines,  Iowa,  50314,  United States; Recruiting
      Siouxland Hematology-Oncology, Sioux City,  Iowa,  51101-1733,  United States; Recruiting
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States; Recruiting
      Via Christi Cancer Center at Via Christi Regional Medical Center, Wichita,  Kansas,  67214,  United States; Recruiting
Kentucky
      Esther Marie Hatton Cancer Care Center at St. Elizabeth Medical Center, Edgewood,  Kentucky,  41017,  United States; Recruiting
Louisiana
      CCOP - Ochsner, New Orleans,  Louisiana,  70121,  United States; Recruiting
      Louisiana State University Medical Center, Lafayette,  Louisiana,  70502-4016,  United States; Recruiting
Maryland
      DeCesaris Cancer Institute at Anne Arundel Medical Center, Annapolis,  Maryland,  21401,  United States; Recruiting
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231-2410,  United States; Recruiting
Michigan
      CCOP - Michigan Cancer Research Consortium, Ann Arbor,  Michigan,  48106,  United States; Recruiting
      Upper Michigan Cancer Center at Marquette General Hospital, Marquette,  Michigan,  49855,  United States; Recruiting
      West Michigan Cancer Center, Kalamazoo,  Michigan,  49007,  United States; Recruiting
Minnesota
      CCOP - Metro-Minnesota, Saint Louis Park,  Minnesota,  55416,  United States; Recruiting
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905-0001,  United States; Recruiting
Missouri
      CCOP - Kansas City, Kansas City,  Missouri,  64131,  United States; Recruiting
Nebraska
      CCOP - Missouri Valley Cancer Consortium, Omaha,  Nebraska,  68106,  United States; Recruiting
      Methodist Hospital Cancer Center at Nebraska Methodist Hospital - Omaha, Omaha,  Nebraska,  68114-4199,  United States; Recruiting
Nevada
      CCOP - Southern Nevada Cancer Research Foundation, Las Vegas,  Nevada,  89106,  United States; Recruiting
New Jersey
      John F. Kennedy Medical Center, Edison,  New Jersey,  08818,  United States; Recruiting
      Monmouth Medical Center, Long Branch,  New Jersey,  07740-6395,  United States; Recruiting
      South Jersey Regional Cancer Center, Millville,  New Jersey,  08332,  United States; Recruiting
New York
      James P. Wilmot Cancer Center at University of Rochester Medical Center, Rochester,  New York,  14642,  United States; Recruiting
      Lipson Cancer and Blood Center at Rochester General Hospital, Rochester,  New York,  14621,  United States; Recruiting
North Carolina
      Wayne Memorial Hospital, Incorporated, Goldsboro,  North Carolina,  27533,  United States; Recruiting
North Dakota
      Altru Cancer Center, Grand Forks,  North Dakota,  58201,  United States; Recruiting
      Medcenter One Health System, Bismarck,  North Dakota,  58501-5505,  United States; Recruiting
      Trinity Cancer Care Center, Minot,  North Dakota,  58701,  United States; Recruiting
Ohio
      Akron City Hospital at Summa Health System, Akron,  Ohio,  44304,  United States; Recruiting
      CCOP - Dayton, Dayton,  Ohio,  45429,  United States; Recruiting
      CCOP - Toledo Community Hospital, Toledo,  Ohio,  43623-3456,  United States; Recruiting
Oklahoma
      CCOP - Oklahoma, Tulsa,  Oklahoma,  74136,  United States; Recruiting
      Natalie Warren Bryant Cancer Center at St. Francis Hospital, Tulsa,  Oklahoma,  74136,  United States; Recruiting
Oregon
      Salem Hospital Regional Cancer Center, Salem,  Oregon,  97309-5014,  United States; Recruiting
Pennsylvania
      Albert Einstein Cancer Center, Philadelphia,  Pennsylvania,  19141-3098,  United States; Recruiting
      Allegheny General Hospital, Pittsburgh,  Pennsylvania,  15212-4772,  United States; Recruiting
      Cancer Center at Paoli Memorial Hospital, Paoli,  Pennsylvania,  19301-1792,  United States; Recruiting
      CCOP - Geisinger Clinic and Medical Center, Danville,  Pennsylvania,  17822-2001,  United States; Recruiting
      CCOP - MainLine Health, Wynnewood,  Pennsylvania,  19096,  United States; Recruiting
      Dale and Frances Hughes Cancer Center at Pocono Medical Center, East Stroudsburg,  Pennsylvania,  18301,  United States; Recruiting
      Delaware County Regional Cancer Center at Delaware County Memorial Hospital, Drexel Hill,  Pennsylvania,  19026,  United States; Recruiting
      Fox Chase Cancer Center, Philadelphia,  Pennsylvania,  19111,  United States; Recruiting
      Guthrie Medical Center - Sayre, Sayre,  Pennsylvania,  18840,  United States; Recruiting
      John and Dorothy Morgan Cancer Center at Lehigh Valley Hospital, Allentown,  Pennsylvania,  18105-1556,  United States; Recruiting
      Kimmel Cancer Center at Thomas Jefferson University - Philadelphia, Philadelphia,  Pennsylvania,  19107-5541,  United States; Recruiting
      Lankenau Cancer Center at Lankenau Hospital, Wynnewood,  Pennsylvania,  19096,  United States; Recruiting
      Mercy Hospital Cancer Center - Scranton, Scranton,  Pennsylvania,  18501,  United States; Recruiting
      Mercy Hospital of Pittsburgh, Pittsburgh,  Pennsylvania,  15219,  United States; Recruiting
      Reading Hospital and Medical Center, Reading,  Pennsylvania,  19612-6052,  United States; Recruiting
South Carolina
      CCOP - Upstate Carolina, Spartanburg,  South Carolina,  29303,  United States; Recruiting
South Dakota
      Avera McKennan Hospital and University Health Center, Sioux Falls,  South Dakota,  57105-1080,  United States; Recruiting
      CCOP - Sioux Community Cancer Consortium, Sioux Falls,  South Dakota,  57104,  United States; Recruiting
      Medical X-Ray Center, Sioux Falls,  South Dakota,  57105,  United States; Recruiting
      Rapid City Regional Hospital, Rapid City,  South Dakota,  57709,  United States; Recruiting
      Sioux Valley Hospital and University of South Dakota Medical Center, Sioux Falls,  South Dakota,  57117-5039,  United States; Recruiting
Texas
      CCOP - Scott and White Hospital, Temple,  Texas,  76508,  United States; Recruiting
      MD Anderson Cancer Center at University of Texas, Houston,  Texas,  77030-4009,  United States; Recruiting
Utah
      Dixie Regional Medical Center, Saint George,  Utah,  84770,  United States; Recruiting
      LDS Hospital, Salt Lake City,  Utah,  84143,  United States; Recruiting
Virginia
      Bon Secours Cancer Care at St. Mary's Hospital, Richmond,  Virginia,  23226,  United States; Recruiting
Washington
      Cancer Institute at Virginia Mason Medical Center, Seattle,  Washington,  98111,  United States; Recruiting
      Yakima Valley Memorial Hospital, Yakima,  Washington,  98902,  United States; Recruiting
West Virginia
      West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division, Charleston,  West Virginia,  25302,  United States; Recruiting
Wisconsin
      CCOP - Marshfield Clinic Research Foundation, Marshfield,  Wisconsin,  54449,  United States; Recruiting
      CCOP - St. Vincent Hospital Cancer Center, Green Bay, Green Bay,  Wisconsin,  54301,  United States; Recruiting
      Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center, La Crosse,  Wisconsin,  54601,  United States; Recruiting
      Medical College of Wisconsin Cancer Center, Milwaukee,  Wisconsin,  53226-3596,  United States; Recruiting
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-0001,  United States; Recruiting
Canada, Quebec
      McGill Cancer Centre at McGill University, Montreal,  Quebec,  H2W 1S6,  Canada; Recruiting
Canada, Saskatchewan
      Allan Blair Cancer Centre at Pasqua Hospital, Regina,  Saskatchewan,  S4T 7T1,  Canada; Recruiting

Study chairs or principal investigators

Susan Marina Chang, MD,  Study Chair,  University of California, San Francisco   
Kurt A. Jaeckle, MD,  Study Chair,  Mayo Clinic - Jacksonville   
Peter Bushunow, MD,  Study Chair,  Lipson Cancer and Blood Center at Rochester General Hospital   

Study ID Numbers:  CDR0000067512; RTOG-9813; ECOG-R9813; NCCTG-RTOG-9813; NCT00004259
Record last reviewed:  February 2005
Last Updated:  April 5, 2005
Record first received:  January 28, 2000
ClinicalTrials.gov Identifier:  NCT00004259
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08