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

NCT ID: NCT00004259

Last Updated: 2019-09-12

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

230 participants

Study Classification

INTERVENTIONAL

Study Start Date

2000-06-30

Study Completion Date

2018-05-14

Brief Summary

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RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy, such as temozolomide, carmustine, and lomustine, 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 or lomustine in treating patients with anaplastic astrocytoma or mixed gliomas.

Detailed Description

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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

* Pilot Arms I and II: Prior to initiating the randomization to 1 of 3 treatment arms in phase III, Patients are accrued to Arm III regimen to determine tolerability.

Phase III

* Patients are randomized to 1 of 2 treatment arms (3rd arm was dropped).

* 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 (dropped, did not open): 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: Phase I: 30 patients; Phase III: 454 patients (227 per treatment arm) within 4 years.

Conditions

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Brain and Central Nervous System Tumors

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Phase I (sequential) followed by phase III (parallel)
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Radiation therapy + temozolomide (TMZ)

Radiation therapy (RT) for 6 weeks concurrent with and followed by TMZ 200mg/m2 for twelve 28-day cycles

Group Type EXPERIMENTAL

TMZ 200mg/m2

Intervention Type DRUG

200 mg/m2 orally on days 1-5 of the first week of radiotherapy. Repeat every 28 days for a total of 12 cycles.

radiation therapy

Intervention Type RADIATION

1.8 Gy fractions (to isocenter), 1 fraction per day, 5 days per week to a dose of 59.4 Gy in 33 fractions.

RT + BCNU/CCNU

Radiation therapy for 6 weeks concurrent with and followed by BCNU 80mg/m2 or CCNU 130 mg/m2 for six 8-week cycles

Group Type ACTIVE_COMPARATOR

BCNU 80mg/m2

Intervention Type DRUG

BCNU 80 mg/m2 will be administered as an intravenous infusion on days 1, 2, and 3 of the first week of radiotherapy and on days 56, 57, and 58, then every eight weeks for four more cycles for a total of 6 cycles (maximum BCNU dose 1440 mg/m2).

radiation therapy

Intervention Type RADIATION

1.8 Gy fractions (to isocenter), 1 fraction per day, 5 days per week to a dose of 59.4 Gy in 33 fractions.

CCNU

Intervention Type DRUG

CCNU at 130 mg/m2 orally every 8 weeks for a total of 6 cycles. Administered on day 1 of the first week of radiotherapy and on day 56, then administered every 8 weeks for four more cycles for a total of 6 cycles.

Pilot Arm #1: RT+TMZ+BCNU

Radiation therapy for 6 weeks concurrent with and followed by BCNU 200mg/m2 and TMZ 150mg/m2 six 6-week cycles

Group Type EXPERIMENTAL

radiation therapy

Intervention Type RADIATION

1.8 Gy fractions (to isocenter), 1 fraction per day, 5 days per week to a dose of 59.4 Gy in 33 fractions.

BCNU 200mg/m2

Intervention Type DRUG

BCNU 200 mg/m2 will be administered as an intravenous infusion on day 1 of radiotherapy and will be repeated every six weeks for a total of 6 cycles (maximum BCNU dose 1200 mg/m2).

TMZ 150mg/m2 six 6-week cycles

Intervention Type DRUG

150 mg/m2 orally on days 1-5 of the first week of radiotherapy. Repeat for a total of six 6-week cycles

Pilot Arm #2: RT+TMZ+BCNU

Radiation therapy for 6 weeks concurrent with and followed by BCNU 150mg/m2 and TMZ 150mg/m2 six 8-week cycles

Group Type EXPERIMENTAL

radiation therapy

Intervention Type RADIATION

1.8 Gy fractions (to isocenter), 1 fraction per day, 5 days per week to a dose of 59.4 Gy in 33 fractions.

BCNU 150mg/m2

Intervention Type DRUG

BCNU 150 mg/m2 will be administered as an intravenous infusion on day 5 of radiotherapy, and it will be repeated every eight weeks for a total of six cycles (maximum total BCNU dose 900 mg/m2).

TMZ 150mg/m2 six 8-week cycles

Intervention Type DRUG

150 mg/m2 orally on days 1-5 of the first week of radiotherapy. Repeat for a total of six 8-week cycles

Interventions

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BCNU 80mg/m2

BCNU 80 mg/m2 will be administered as an intravenous infusion on days 1, 2, and 3 of the first week of radiotherapy and on days 56, 57, and 58, then every eight weeks for four more cycles for a total of 6 cycles (maximum BCNU dose 1440 mg/m2).

Intervention Type DRUG

TMZ 200mg/m2

200 mg/m2 orally on days 1-5 of the first week of radiotherapy. Repeat every 28 days for a total of 12 cycles.

Intervention Type DRUG

radiation therapy

1.8 Gy fractions (to isocenter), 1 fraction per day, 5 days per week to a dose of 59.4 Gy in 33 fractions.

Intervention Type RADIATION

CCNU

CCNU at 130 mg/m2 orally every 8 weeks for a total of 6 cycles. Administered on day 1 of the first week of radiotherapy and on day 56, then administered every 8 weeks for four more cycles for a total of 6 cycles.

Intervention Type DRUG

BCNU 150mg/m2

BCNU 150 mg/m2 will be administered as an intravenous infusion on day 5 of radiotherapy, and it will be repeated every eight weeks for a total of six cycles (maximum total BCNU dose 900 mg/m2).

Intervention Type DRUG

BCNU 200mg/m2

BCNU 200 mg/m2 will be administered as an intravenous infusion on day 1 of radiotherapy and will be repeated every six weeks for a total of 6 cycles (maximum BCNU dose 1200 mg/m2).

Intervention Type DRUG

TMZ 150mg/m2 six 6-week cycles

150 mg/m2 orally on days 1-5 of the first week of radiotherapy. Repeat for a total of six 6-week cycles

Intervention Type DRUG

TMZ 150mg/m2 six 8-week cycles

150 mg/m2 orally on days 1-5 of the first week of radiotherapy. Repeat for a total of six 8-week cycles

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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)
* Aspartate aminotransferase (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
Minimum Eligible Age

18 Years

Maximum Eligible Age

120 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

North Central Cancer Treatment Group

NETWORK

Sponsor Role collaborator

Eastern Cooperative Oncology Group

NETWORK

Sponsor Role collaborator

NRG Oncology

OTHER

Sponsor Role collaborator

Radiation Therapy Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Susan M. Chang, MD

Role: STUDY_CHAIR

University of California, San Francisco

Kurt A. Jaeckle, MD

Role: STUDY_CHAIR

Mayo Clinic

Peter Bushunow, MD

Role: STUDY_CHAIR

Lipson Cancer and Blood Center at Rochester General Hospital

Locations

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Mobile Infirmary Medical Center

Mobile, Alabama, United States

Site Status

Arizona Oncology Services Foundation

Phoenix, Arizona, United States

Site Status

Enloe Cancer Center at Enloe Medical Center

Chico, California, United States

Site Status

North Bay Cancer Center

Fairfield, California, United States

Site Status

Solano Radiation Oncology Center

Vacaville, California, United States

Site Status

Lynn Regional Cancer Center at Boca Raton Community Hospital - Main Center

Boca Raton, Florida, United States

Site Status

University of Florida Shands Cancer Center

Gainesville, Florida, United States

Site Status

Baptist Cancer Institute - Jacksonville

Jacksonville, Florida, United States

Site Status

Florida Oncology Associates at Southside Cancer Center

Jacksonville, Florida, United States

Site Status

Baptist Medical Center South

Jacksonville, Florida, United States

Site Status

Integrated Community Oncology Network

Jacksonville Beach, Florida, United States

Site Status

Florida Oncology Associates

Orange Park, Florida, United States

Site Status

Florida Cancer Center - Palatka

Palatka, Florida, United States

Site Status

Flagler Cancer Center

Saint Augustine, Florida, United States

Site Status

H. Lee Moffitt Cancer Center and Research Institute at University of South Florida

Tampa, Florida, United States

Site Status

John B. Amos Cancer Center

Columbus, Georgia, United States

Site Status

St. Joseph Medical Center

Bloomington, Illinois, United States

Site Status

Graham Hospital

Canton, Illinois, United States

Site Status

Memorial Hospital

Carthage, Illinois, United States

Site Status

Eureka Community Hospital

Eureka, Illinois, United States

Site Status

Galesburg Clinic

Galesburg, Illinois, United States

Site Status

Galesburg Cottage Hospital

Galesburg, Illinois, United States

Site Status

InterCommunity Cancer Center of Western Illinois

Galesburg, Illinois, United States

Site Status

Mason District Hospital

Havana, Illinois, United States

Site Status

Hopedale Medical Complex

Hopedale, Illinois, United States

Site Status

Kewanee Hospital

Kewanee, Illinois, United States

Site Status

McDonough District Hospital

Macomb, Illinois, United States

Site Status

BroMenn Regional Medical Center

Normal, Illinois, United States

Site Status

Community Cancer Center

Normal, Illinois, United States

Site Status

Community Hospital of Ottawa

Ottawa, Illinois, United States

Site Status

Oncology Hematology Associates of Central Illinois, PC - Ottawa

Ottawa, Illinois, United States

Site Status

Cancer Treatment Center at Pekin Hospital

Pekin, Illinois, United States

Site Status

Proctor Hospital

Peoria, Illinois, United States

Site Status

OSF St. Francis Medical Center

Peoria, Illinois, United States

Site Status

CCOP - Illinois Oncology Research Association

Peoria, Illinois, United States

Site Status

Oncology Hematology Associates of Central Illinois, PC - Peoria

Peoria, Illinois, United States

Site Status

Methodist Medical Center of Illinois

Peoria, Illinois, United States

Site Status

Illinois Valley Community Hospital

Peru, Illinois, United States

Site Status

Perry Memorial Hospital

Princeton, Illinois, United States

Site Status

St. Margaret's Hospital

Spring Valley, Illinois, United States

Site Status

Valley Cancer Center

Spring Valley, Illinois, United States

Site Status

McFarland Clinic, PC

Ames, Iowa, United States

Site Status

Cancer Center of Kansas, PA - Chanute

Chanute, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Dodge City

Dodge City, Kansas, United States

Site Status

Cancer Center of Kansas, PA - El Dorado

El Dorado, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Kingman

Kingman, Kansas, United States

Site Status

Southwest Medical Center

Liberal, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Newton

Newton, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Parsons

Parsons, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Pratt

Pratt, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Salina

Salina, Kansas, United States

Site Status

Cotton-O'Neil Cancer Center

Topeka, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Wellington

Wellington, Kansas, United States

Site Status

Associates in Womens Health, PA - North Review

Wichita, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Medical Arts Tower

Wichita, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Wichita

Wichita, Kansas, United States

Site Status

CCOP - Wichita

Wichita, Kansas, United States

Site Status

Via Christi Cancer Center at Via Christi Regional Medical Center

Wichita, Kansas, United States

Site Status

Wesley Medical Center

Wichita, Kansas, United States

Site Status

Cancer Center of Kansas, PA - Winfield

Winfield, Kansas, United States

Site Status

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, United States

Site Status

West Michigan Cancer Center

Kalamazoo, Michigan, United States

Site Status

CCOP - Duluth

Duluth, Minnesota, United States

Site Status

St. John's Regional Health Center

Springfield, Missouri, United States

Site Status

CCOP - Montana Cancer Consortium

Billings, Montana, United States

Site Status

Deaconess Billings Clinic - Downtown

Billings, Montana, United States

Site Status

Good Samaritan Cancer Center at Good Samaritan Hospital

Kearney, Nebraska, United States

Site Status

Methodist Cancer Center at Methodist Hospital - Omaha

Omaha, Nebraska, United States

Site Status

University Medical Center of Southern Nevada

Las Vegas, Nevada, United States

Site Status

CCOP - Nevada Cancer Research Foundation

Las Vegas, Nevada, United States

Site Status

Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton

Marlton, New Jersey, United States

Site Status

Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare

Vineland, New Jersey, United States

Site Status

Fox Chase Virtua Health Cancer Program at Virtua West Jersey

Voorhees Township, New Jersey, United States

Site Status

Lipson Cancer and Blood Center at Rochester General Hospital

Rochester, New York, United States

Site Status

Mission Hospitals - Memorial Campus

Asheville, North Carolina, United States

Site Status

Akron City Hospital

Akron, Ohio, United States

Site Status

Charles M. Barrett Cancer Center at University Hospital

Cincinnati, Ohio, United States

Site Status

Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Site Status

Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford

Salem, Ohio, United States

Site Status

Cancer Treatment Center

Wooster, Ohio, United States

Site Status

Natalie Warren Bryant Cancer Center at St. Francis Hospital

Tulsa, Oklahoma, United States

Site Status

Kimmel Cancer Center at Thomas Jefferson University - Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Allegheny Cancer Center at Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Site Status

Reading Hospital and Medical Center

Reading, Pennsylvania, United States

Site Status

Guthrie Cancer Center at Guthrie Clinic Sayre

Sayre, Pennsylvania, United States

Site Status

Rapid City Regional Hospital

Rapid City, South Dakota, United States

Site Status

Latter Day Saints Hospital

Salt Lake City, Utah, United States

Site Status

Theda Care Cancer Institute

Appleton, Wisconsin, United States

Site Status

St. Vincent Hospital Regional Cancer Center

Green Bay, Wisconsin, United States

Site Status

Bay Area Cancer Care Center at Bay Area Medical Center

Marinette, Wisconsin, United States

Site Status

Community Memorial Hospital Cancer Care Center

Menomonee Falls, Wisconsin, United States

Site Status

University of Wisconcin Cancer Center at Aspirus Wausau Hospital

Wausau, Wisconsin, United States

Site Status

Countries

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United States

References

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Chang SM, Seiferheld W, Curran W, Share R, Atkins J, Choucair A, Kresl J, Thoron L, Cairncross G, Gilbert M, Bahary JP, Dolinskas C, Louis DN, Bushunow P, Buckner J, Barger G, Mehta M. 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. 2004 Jul 15;59(4):1122-6. doi: 10.1016/j.ijrobp.2004.01.002.

Reference Type RESULT
PMID: 15234047 (View on PubMed)

Other Identifiers

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CDR0000067512

Identifier Type: -

Identifier Source: secondary_id

ECOG-R9813

Identifier Type: -

Identifier Source: secondary_id

NCCTG-RTOG-9813

Identifier Type: -

Identifier Source: secondary_id

RTOG-9813

Identifier Type: -

Identifier Source: org_study_id

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