RATIONALE: Biological therapies such as gefitinib may interfere with the growth of the tumor cells and slow the growth of the tumor. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining gefitinib with radiation therapy may kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of combining gefitinib with radiation therapy in treating patients who have glioblastoma multiforme.

Condition	Treatment or Intervention	Phase
adult glioblastoma multiforme	Drug: gefitinib  Procedure: enzyme inhibitor therapy  Procedure: protein tyrosine kinase inhibitor therapy  Procedure: radiation therapy	Phase I Phase II

Further Study Details: 

OBJECTIVES:

• Determine the maximum tolerated dose of gefitinib when given concurrently with cranial radiotherapy in patients with glioblastoma multiforme.
• Determine the overall survival and progression-free survival of patients treated with this regimen.
• Determine the feasibility and toxicity of this regimen in these patients.

OUTLINE: This is a multicenter, dose-escalation study of gefitinib. Patients are stratified according to whether they are concurrently receiving enzyme-inducing anticonvulsant drugs (EIACD) (yes vs no).

• Patients receive oral gefitinib once daily for 7 weeks. Beginning 1 week after initiation of gefitinib, patients undergo cranial radiotherapy once daily 5 days a week for 6 weeks. After the completion of radiotherapy, patients continue to receive oral gefitinib once daily for 18 months in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of gefitinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
• Phase II:Patient receive oral gefitinib at the MTD as in phase I. Patients undergo cranial radiotherapy as in phase I. Patients in both phases are followed every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 30 patients (18 enzyme-inducing anticonvulsant drug [EIACD] patients and 12 non-EIACD patients) will be accrued for phase I of this study within 2 months. A maximum of 140 patients will be accrued for phase II of this study within 10 months.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed glioblastoma multiforme with areas of necrosis
• Tumor must be supratentorial
• Diagnosis made by surgical biopsy or excision
• No recurrent or multifocal disease
• No metastases detected below the tentorium or beyond the cranial vault
• Tumor tissue and serum samples required

PATIENT CHARACTERISTICS: Age:

• Adult

Performance status:

• Zubrod 0-1

Life expectancy:

• At least 8 weeks

Hematopoietic:

• Hemoglobin at least 10 g/dL (transfusions allowed)
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 2.0 mg/dL
• SGPT or SGOT no greater than 2 times normal

Renal:

• Creatinine no greater than 1.5 mg/dL
• BUN no greater than 25 mg/dL

Other:

• No known AIDS
• No other major medical illness or psychiatric impairment that would preclude study participation
• No active connective tissue disorders, including lupus and scleroderma
• No known multiple sclerosis
• No other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix or bladder
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy or radiosensitizers for cancers of the head and neck

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy to the head and neck except for T1 glottic tumors

Surgery:

• See Disease Characteristics
• No more than 5 weeks since prior surgery and recovered
• No concurrent ophthalmic surgery

Other:

• At least 30 days since prior participation in another clinical study
• No concurrent participation in another clinical study
• No concurrent systemic retinoids or herbal medicines
• No concurrent drugs that induce CytP4503A4 except enzyme-inducing anticonvulsant drugs

Alabama
      Mobile Infirmary Medical Center, Mobile,  Alabama,  36652-2144,  United States
Arizona
      Foundation for Cancer Research and Education, Phoenix,  Arizona,  85013,  United States
California
      CCOP - Bay Area Tumor Institute, Oakland,  California,  94609-3305,  United States
      Pomona Valley Hospital Medical Center, Pomona,  California,  91767,  United States
Colorado
      Memorial Hospital Cancer Center, Colorado Springs,  Colorado,  80909,  United States
      University of Colorado Cancer Center at University of Colorado Health Sciences Center, Denver,  Colorado,  80010,  United States
Connecticut
      Yale Comprehensive Cancer Center, New Haven,  Connecticut,  06520-8040,  United States
Delaware
      CCOP - Christiana Care Health Services, Newark,  Delaware,  19713,  United States
Florida
      Baptist Hospital of Miami, Miami,  Florida,  33256-2110,  United States
      H. Lee Moffitt Cancer Center and Research Institute, Tampa,  Florida,  33612-9497,  United States
      University of Miami Sylvester Cancer Center, Miami,  Florida,  33136,  United States
Idaho
      Saint Alphonsus Regional Medical Center, Boise,  Idaho,  83706,  United States
Illinois
      Alexian Brothers Cancer Care Center, Elk Grove Village,  Illinois,  60007,  United States
      Ingalls Memorial Hospital, Harvey,  Illinois,  60426,  United States
      Northwest Community Hospital, Arlington Heights,  Illinois,  60005,  United States
Indiana
      Union Hospital, Terre Haute,  Indiana,  47804,  United States
Iowa
      Alegent Health Community Memorial Hospital, Missouri Valley,  Iowa,  51555-1199,  United States
      Burgess Health Center, Onawa,  Iowa,  51040,  United States
Kentucky
      Markey Cancer Center at University of Kentucky Chandler Medical Center, Lexington,  Kentucky,  40536-0293,  United States
Louisiana
      Baton Rouge General Medical Center, Baton Rouge,  Louisiana,  70821-2511,  United States
      Mary Bird Perkins Cancer Center, Baton Rouge,  Louisiana,  70809,  United States
      MBCCOP - LSU Health Sciences Center, New Orleans,  Louisiana,  70112,  United States
      Stanley S. Scott Cancer Center at Louisiana State University Medical Center - New Orleans, New Orleans,  Louisiana,  70140-1015,  United States
      Tulane University School of Medicine, New Orleans,  Louisiana,  70112-2699,  United States
Massachusetts
      Massachusetts General Hospital, Boston,  Massachusetts,  02114,  United States
Michigan
      West Michigan Cancer Center, Kalamazoo,  Michigan,  49007,  United States
Minnesota
      CCOP - Metro-Minnesota, Saint Louis Park,  Minnesota,  55416,  United States
      Fairview University Medical Center - University Campus, Minneapolis,  Minnesota,  55455,  United States
      Hubert H. Humphrey Cancer Center at North Memorial Medical Center, Robbinsdale,  Minnesota,  55422,  United States
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905-0001,  United States
      Mercy Hospital, Coon Rapids,  Minnesota,  55433,  United States
      Ridgeview Medical Center, Waconia,  Minnesota,  55387,  United States
      United Hospital, Saint Paul,  Minnesota,  55102,  United States
Nebraska
      Alegent Health - Immanuel Medical Center, Omaha,  Nebraska,  68122,  United States
      Bergan Mercy Medical Center, Omaha,  Nebraska,  68124,  United States
      CCOP - Missouri Valley Cancer Consortium, Omaha,  Nebraska,  68106,  United States
      Creighton University Medical Center, Omaha,  Nebraska,  68131-2197,  United States
      Methodist Hospital Cancer Center at Nebraska Methodist Hospital - Omaha, Omaha,  Nebraska,  68114-4199,  United States
      Midlands Cancer Center at Midlands Community Hospital, Papillion,  Nebraska,  68046-4194,  United States
New Jersey
      Monmouth Medical Center, Long Branch,  New Jersey,  07740-6395,  United States
New York
      New York Methodist Hospital, Brooklyn,  New York,  11215,  United States
North Carolina
      Moses Cone Regional Cancer Center at Wesley Long Community Hospital, Greensboro,  North Carolina,  27403-1199,  United States
      Wayne Memorial Hospital, Inc., Goldsboro,  North Carolina,  27533,  United States
Ohio
      Akron City Hospital, Akron,  Ohio,  44304,  United States
      Akron General Medical Center, Akron,  Ohio,  44302,  United States
      Cancer Care Center, Incorporated, Salem,  Ohio,  44460,  United States
      Cancer Treatment Center, Wooster,  Ohio,  44691,  United States
Oklahoma
      Frank C. Love Cancer Institute at St. Anthony Hospital, Oklahoma City,  Oklahoma,  73102,  United States
Pennsylvania
      Bryn Mawr Hospital, Bryn Mawr,  Pennsylvania,  19010,  United States
      CCOP - MainLine Health, Wynnewood,  Pennsylvania,  19096,  United States
      Fox Chase Cancer Center, Philadelphia,  Pennsylvania,  19111,  United States
      Kimmel Cancer Center at Thomas Jefferson University - Philadelphia, Philadelphia,  Pennsylvania,  19107-5541,  United States
      Lankenau Cancer Center at Lankenau Hospital, Wynnewood,  Pennsylvania,  19096,  United States
      Mercy Hospital Cancer Center - Scranton, Scranton,  Pennsylvania,  18501,  United States
      Mercy Hospital of Pittsburgh, Pittsburgh,  Pennsylvania,  15219,  United States
      Paoli Memorial Hospital, Paoli,  Pennsylvania,  19301-1792,  United States
      Pocono Cancer Center, East Stroudsburg,  Pennsylvania,  18301,  United States
      Wellspan Health - York Cancer Center, York,  Pennsylvania,  17403,  United States
      Western Pennsylvania Hospital, Pittsburgh,  Pennsylvania,  15224,  United States
South Carolina
      Gibbs Regional Cancer Center at Spartanburg Regional Medical Center, Spartanburg,  South Carolina,  29303,  United States
South Dakota
      Rapid City Regional Hospital, Rapid City,  South Dakota,  57709,  United States
Tennessee
      West Tennessee Cancer Center at Jackson-Madison County General Hospital, Jackson,  Tennessee,  38301,  United States
Utah
      Dixie Regional Medical Center, Saint George,  Utah,  84770,  United States
      LDS Hospital, Salt Lake City,  Utah,  84143,  United States
      McKay-Dee Hospital Center, Ogden,  Utah,  84403,  United States
      Utah Valley Regional Medical Center - Provo, Provo,  Utah,  84604,  United States
Vermont
      Vermont Cancer Center at University of Vermont, Burlington,  Vermont,  05405-0075,  United States
Virginia
      Bon Secours - St. Mary's Hospital, Richmond,  Virginia,  23226,  United States
      Cancer Center at the University of Virginia, Charlottesville,  Virginia,  22908,  United States
Washington
      Yakima Valley Memorial Hospital, Yakima,  Washington,  98902,  United States
Wisconsin
      All Saints Cancer Center at All Saints Healthcare, Racine,  Wisconsin,  53405,  United States
      CCOP - Marshfield Clinic Research Foundation, Marshfield,  Wisconsin,  54449,  United States
      Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center, La Crosse,  Wisconsin,  54601,  United States
      Medical College of Wisconsin Cancer Center, Milwaukee,  Wisconsin,  53226,  United States
      St. Vincent Hospital, Green Bay,  Wisconsin,  54307-3508,  United States
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-6164,  United States

Study chairs or principal investigators

Arnab Chakravarti, MD,  Study Chair,  Massachusetts General Hospital   

Study ID Numbers:  CDR0000069330; RTOG-0211; RTOG-BR-0211; RTOG-DEV-1007
Record last reviewed:  June 2004
Last Updated:  October 13, 2004
Record first received:  January 24, 2003
ClinicalTrials.gov Identifier:  NCT00052208
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08