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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)


Phase 3
18 Years
N/A
Open (Enrolling)
Both
Brain and Central Nervous System Tumors

Thank you

Trial Information

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)


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 or lomustine 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
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.

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)

Inclusion 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 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

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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Outcome Measure:

Overall survival (OS)

Safety Issue:

No

Principal Investigator

Susan M. Chang, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of California, San Francisco

Authority:

United States: Federal Government

Study ID:

CDR0000067512

NCT ID:

NCT00004259

Start Date:

June 2000

Completion Date:

Related Keywords:

  • Brain and Central Nervous System Tumors
  • adult anaplastic astrocytoma
  • adult mixed glioma
  • Astrocytoma
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms
  • Glioma

Name

Location

Akron City Hospital Akron, Ohio  44304
CCOP - Wichita Wichita, Kansas  67214-3882
CCOP - Illinois Oncology Research Association Peoria, Illinois  61602
West Michigan Cancer Center Kalamazoo, Michigan  49007-3731
CCOP - Duluth Duluth, Minnesota  55805
Case Comprehensive Cancer Center Cleveland, Ohio  44106-5065
Natalie Warren Bryant Cancer Center at St. Francis Hospital Tulsa, Oklahoma  74136
Rapid City Regional Hospital Rapid City, South Dakota  57709
Methodist Medical Center of Illinois Peoria, Illinois  61636
CCOP - Montana Cancer Consortium Billings, Montana  59101
Reading Hospital and Medical Center Reading, Pennsylvania  19612-6052
Charles M. Barrett Cancer Center at University Hospital Cincinnati, Ohio  45267-0526
Kimmel Cancer Center at Thomas Jefferson University - Philadelphia Philadelphia, Pennsylvania  19107
Wesley Medical Center Wichita, Kansas  67214
Mobile Infirmary Medical Center Mobile, Alabama  36640-0460
St. John's Regional Health Center Springfield, Missouri  65804
Latter Day Saints Hospital Salt Lake City, Utah  84143
University of Florida Shands Cancer Center Gainesville, Florida  32610-0232
Via Christi Cancer Center at Via Christi Regional Medical Center Wichita, Kansas  67214
Mission Hospitals - Memorial Campus Asheville, North Carolina  28801
St. Vincent Hospital Regional Cancer Center Green Bay, Wisconsin  54307-3508
Bay Area Cancer Care Center at Bay Area Medical Center Marinette, Wisconsin  54143
Baptist Cancer Institute - Jacksonville Jacksonville, Florida  32207
Southwest Medical Center Liberal, Kansas  67901
Deaconess Billings Clinic - Downtown Billings, Montana  59101
Greenebaum Cancer Center at University of Maryland Medical Center Baltimore, Maryland  21201
CCOP - Nevada Cancer Research Foundation Las Vegas, Nevada  89109-2306
Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton Marlton, New Jersey  08053
Fox Chase Virtua Health Cancer Program at Virtua West Jersey Voorhees, New Jersey  08043
University Medical Center of Southern Nevada Las Vegas, Nevada  89102
North Bay Cancer Center Fairfield, California  94533
St. Joseph Medical Center Bloomington, Illinois  61701
Graham Hospital Canton, Illinois  61520
Memorial Hospital Carthage, Illinois  62321
Eureka Community Hospital Eureka, Illinois  61530
Galesburg Cottage Hospital Galesburg, Illinois  61401
Galesburg Clinic Galesburg, Illinois  61401
InterCommunity Cancer Center of Western Illinois Galesburg, Illinois  61401
Mason District Hospital Havana, Illinois  62644
Hopedale Medical Complex Hopedale, Illinois  61747
Kewanee Hospital Kewanee, Illinois  61443
McDonough District Hospital Macomb, Illinois  61455
BroMenn Regional Medical Center Normal, Illinois  61761
Community Cancer Center Normal, Illinois  61761
Community Hospital of Ottawa Ottawa, Illinois  61350
Oncology Hematology Associates of Central Illinois, PC - Ottawa Ottawa, Illinois  61350
Cancer Treatment Center at Pekin Hospital Pekin, Illinois  61554
Oncology Hematology Associates of Central Illinois, PC - Peoria Peoria, Illinois  61615
OSF St. Francis Medical Center Peoria, Illinois  61637
Proctor Hospital Peoria, Illinois  61614
Illinois Valley Community Hospital Peru, Illinois  61354
Perry Memorial Hospital Princeton, Illinois  61356
St. Margaret's Hospital Spring Valley, Illinois  61362
Valley Cancer Center Spring Valley, Illinois  61362
Cancer Center of Kansas, PA - Dodge City Dodge City, Kansas  67801
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida Tampa, Florida  33612
Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford Salem, Ohio  44460
Cancer Treatment Center Wooster, Ohio  44691
Allegheny Cancer Center at Allegheny General Hospital Pittsburgh, Pennsylvania  15212
John B. Amos Cancer Center Columbus, Georgia  31904
McFarland Clinic, PC Ames, Iowa  50010
Cancer Center of Kansas, PA - Chanute Chanute, Kansas  66720
Cancer Center of Kansas, PA - El Dorado El Dorado, Kansas  67042
Cancer Center of Kansas, PA - Kingman Kingman, Kansas  67068
Cancer Center of Kansas, PA - Newton Newton, Kansas  67114
Cancer Center of Kansas, PA - Parsons Parsons, Kansas  67357
Cancer Center of Kansas, PA - Pratt Pratt, Kansas  67124
Cancer Center of Kansas, PA - Salina Salina, Kansas  67401
Cotton-O'Neil Cancer Center Topeka, Kansas  66606
Cancer Center of Kansas, PA - Wellington Wellington, Kansas  67152
Cancer Center of Kansas, PA - Wichita Wichita, Kansas  67214
Associates in Womens Health, PA - North Review Wichita, Kansas  67208
Cancer Center of Kansas, PA - Medical Arts Tower Wichita, Kansas  67208
Cancer Center of Kansas, PA - Winfield Winfield, Kansas  67156
Guthrie Cancer Center at Guthrie Clinic Sayre Sayre, Pennsylvania  18840
Methodist Cancer Center at Methodist Hospital - Omaha Omaha, Nebraska  68114
Arizona Oncology Services Foundation Phoenix, Arizona  85013
Enloe Cancer Center at Enloe Medical Center Chico, California  95926
Good Samaritan Cancer Center at Good Samaritan Hospital Kearney, Nebraska  68848-1990
Theda Care Cancer Institute Appleton, Wisconsin  54911
Community Memorial Hospital Cancer Care Center Menomonee Falls, Wisconsin  53051
University of Wisconcin Cancer Center at Aspirus Wausau Hospital Wausau, Wisconsin  54401
Solano Radiation Oncology Center Vacaville, California  95687
Lynn Regional Cancer Center at Boca Raton Community Hospital - Main Center Boca Raton, Florida  33486
Florida Oncology Associates at Southside Cancer Center Jacksonville, Florida  32207
Integrated Community Oncology Network Jacksonville Beach, Florida  32250
Baptist Medical Center South Jascksonville, Florida  32258
Florida Oncology Associates Orange Park, Florida  32073
Florida Cancer Center - Palatka Palatka, Florida  32177
Flagler Cancer Center Saint Augustine, Florida  32086
Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare Vineland, New Jersey  08360
Lipson Cancer and Blood Center at Rochester General Hospital Rochester, New York  14621