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

NCT00004259 | Completed Phase 3 Results DMC

• 4 other identifiers: RTOG-9813CDR0000067512ECOG-R9813NCCTG-RTOG-9813
• Study Type: interventional
• Target: 230
• Locations: 1 country
• Sites: 92

Brief Summary

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.

Conditions

Brain and Central Nervous System Tumors

Keywords

adult anaplastic astrocytoma; adult mixed glioma

Outcome Measures

Primary Outcomes (2)

• (Phase III) Overall Survival (OS)

  Survival time is defined as time from randomization to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. Per the protocol, the pilot arms were not included in the Phase III analyses.

  From randomization to date of death. Patients are followed until death. Analysis occurs after 155 deaths have been reported, estimated at 5.5 years from the study opening.

• (Phase I) Number of Subjects With Dose Limiting Toxicities (DLT) on the Two Pilot Arms

  Adverse events were graded using CTCAE v2.0. Grade refers to the severity of the adverse event (AE). The CTCAE v2.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. Dose limiting toxicity (DLT) was defined as grade 3+ pulmonary toxicity, grade 4+ thrombocytopenia (\< 25,000 for 5 days), neutropenia (\< 500/microl for 7 days), or neutropenia of any duration with fever requiring hospital admission after one dose reduction of 50% in BCNU. A 20% rate of grade 3+ pulmonary toxicities or a 40% rate of grade 4+ thrombocytopenia and neutropenia was considered unacceptable for a treatment arm combining RT, TMZ, and BCNU.

  From start of treatment to 3 months

Secondary Outcomes (4)

• (Phase III) Time to Tumor Progression (TTP)

  From randomization to date of death. Patients are followed until death. Analysis occurs after 155 deaths have been reported, estimated at 5.5 years from the study opening.

• (Phase III) Number of Patients With Grade 3 or Higher Toxicity

  From randomization to date of death. Patients are followed until death. Analysis occurs after 155 deaths have been reported, estimated at 5.5 years from the study opening.

• (Phase III) Survival Time by MGMT Status

  From randomization to date of death. Patients are followed until death. Analysis occurs after 155 deaths have been reported, estimated at 5.5 years from the study opening.

• (Phase III) Progression-free Survival by MGMT Status

  From randomization to date of death. Patients are followed until death. Analysis occurs after 155 deaths have been reported, estimated at 5.5 years from the study opening.

Study Arms (4)

Radiation therapy + temozolomide (TMZ)

EXPERIMENTAL

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

Drug: TMZ 200mg/m2; Radiation: radiation therapy

RT + BCNU/CCNU

ACTIVE COMPARATOR

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

Drug: BCNU 80mg/m2; Radiation: radiation therapy; Drug: CCNU

Pilot Arm #1: RT+TMZ+BCNU

EXPERIMENTAL

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

Radiation: radiation therapy; Drug: BCNU 200mg/m2; Drug: TMZ 150mg/m2 six 6-week cycles

Pilot Arm #2: RT+TMZ+BCNU

EXPERIMENTAL

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

Radiation: radiation therapy; Drug: BCNU 150mg/m2; Drug: TMZ 150mg/m2 six 8-week cycles

Interventions

BCNU 80mg/m2 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).

RT + BCNU/CCNU

TMZ 200mg/m2 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 + temozolomide (TMZ)

radiation therapy 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.

Pilot Arm #1: RT+TMZ+BCNU; Pilot Arm #2: RT+TMZ+BCNU; RT + BCNU/CCNU; Radiation therapy + temozolomide (TMZ)

CCNU 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.

RT + BCNU/CCNU

BCNU 150mg/m2 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).

Pilot Arm #2: RT+TMZ+BCNU

BCNU 200mg/m2 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).

Pilot Arm #1: RT+TMZ+BCNU

TMZ 150mg/m2 six 6-week cycles 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 #1: RT+TMZ+BCNU

TMZ 150mg/m2 six 8-week cycles DRUG

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

Pilot Arm #2: RT+TMZ+BCNU

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically proven unifocal anaplastic astrocytoma or mixed gliomas, including the following: * Anaplastic astrocytoma * 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) * 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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Radiation Therapy Oncology Group: lead
• National Cancer Institute (NCI): collaborator
• North Central Cancer Treatment Group: collaborator
• Eastern Cooperative Oncology Group: collaborator
• NRG Oncology: collaborator

Study Sites (92)

Mobile Infirmary Medical Center

Mobile, Alabama, 36652-2144, United States

Location

Arizona Oncology Services Foundation

Phoenix, Arizona, 85013, United States

Location

Enloe Cancer Center at Enloe Medical Center

Chico, California, 95926, United States

Location

North Bay Cancer Center

Fairfield, California, 94533, United States

Location

Solano Radiation Oncology Center

Vacaville, California, 95687, United States

Location

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

Boca Raton, Florida, 33486, United States

Location

University of Florida Shands Cancer Center

Gainesville, Florida, 32610-0232, United States

Location

Baptist Cancer Institute - Jacksonville

Jacksonville, Florida, 32207, United States

Location

Florida Oncology Associates at Southside Cancer Center

Jacksonville, Florida, 32207, United States

Location

Baptist Medical Center South

Jacksonville, Florida, 32258, United States

Location

Integrated Community Oncology Network

Jacksonville Beach, Florida, 32250, United States

Location

Florida Oncology Associates

Orange Park, Florida, 32073, United States

Location

Florida Cancer Center - Palatka

Palatka, Florida, 32177, United States

Location

Flagler Cancer Center

Saint Augustine, Florida, 32086, United States

Location

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

Tampa, Florida, 33612-9497, United States

Location

John B. Amos Cancer Center

Columbus, Georgia, 31904, United States

Location

St. Joseph Medical Center

Bloomington, Illinois, 61701, United States

Location

Graham Hospital

Canton, Illinois, 61520, United States

Location

Memorial Hospital

Carthage, Illinois, 62321, United States

Location

Eureka Community Hospital

Eureka, Illinois, 61530, United States

Location

Galesburg Clinic

Galesburg, Illinois, 61401, United States

Location

Galesburg Cottage Hospital

Galesburg, Illinois, 61401, United States

Location

InterCommunity Cancer Center of Western Illinois

Galesburg, Illinois, 61401, United States

Location

Mason District Hospital

Havana, Illinois, 62644, United States

Location

Hopedale Medical Complex

Hopedale, Illinois, 61747, United States

Location

Kewanee Hospital

Kewanee, Illinois, 61443, United States

Location

McDonough District Hospital

Macomb, Illinois, 61455, United States

Location

BroMenn Regional Medical Center

Normal, Illinois, 61761, United States

Location

Community Cancer Center

Normal, Illinois, 61761, United States

Location

Community Hospital of Ottawa

Ottawa, Illinois, 61350, United States

Location

Oncology Hematology Associates of Central Illinois, PC - Ottawa

Ottawa, Illinois, 61350, United States

Location

Cancer Treatment Center at Pekin Hospital

Pekin, Illinois, 61554, United States

Location

Proctor Hospital

Peoria, Illinois, 61614, United States

Location

OSF St. Francis Medical Center

Peoria, Illinois, 61615-7827, United States

Location

CCOP - Illinois Oncology Research Association

Peoria, Illinois, 61615, United States

Location

Oncology Hematology Associates of Central Illinois, PC - Peoria

Peoria, Illinois, 61615, United States

Location

Methodist Medical Center of Illinois

Peoria, Illinois, 61636, United States

Location

Illinois Valley Community Hospital

Peru, Illinois, 61354, United States

Location

Perry Memorial Hospital

Princeton, Illinois, 61356, United States

Location

St. Margaret's Hospital

Spring Valley, Illinois, 61362, United States

Location

Valley Cancer Center

Spring Valley, Illinois, 61362, United States

Location

McFarland Clinic, PC

Ames, Iowa, 50010, United States

Location

Cancer Center of Kansas, PA - Chanute

Chanute, Kansas, 66720, United States

Location

Cancer Center of Kansas, PA - Dodge City

Dodge City, Kansas, 67801, United States

Location

Cancer Center of Kansas, PA - El Dorado

El Dorado, Kansas, 67042, United States

Location

Cancer Center of Kansas, PA - Kingman

Kingman, Kansas, 67068, United States

Location

Southwest Medical Center

Liberal, Kansas, 67901, United States

Location

Cancer Center of Kansas, PA - Newton

Newton, Kansas, 67114, United States

Location

Cancer Center of Kansas, PA - Parsons

Parsons, Kansas, 67357, United States

Location

Cancer Center of Kansas, PA - Pratt

Pratt, Kansas, 67124, United States

Location

Cancer Center of Kansas, PA - Salina

Salina, Kansas, 67042, United States

Location

Cotton-O'Neil Cancer Center

Topeka, Kansas, 66604, United States

Location

Cancer Center of Kansas, PA - Wellington

Wellington, Kansas, 67152, United States

Location

Associates in Womens Health, PA - North Review

Wichita, Kansas, 67203, United States

Location

Cancer Center of Kansas, PA - Medical Arts Tower

Wichita, Kansas, 67208, United States

Location

Cancer Center of Kansas, PA - Wichita

Wichita, Kansas, 67214, United States

Location

CCOP - Wichita

Wichita, Kansas, 67214, United States

Location

Via Christi Cancer Center at Via Christi Regional Medical Center

Wichita, Kansas, 67214, United States

Location

Wesley Medical Center

Wichita, Kansas, 67214, United States

Location

Cancer Center of Kansas, PA - Winfield

Winfield, Kansas, 67156, United States

Location

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

West Michigan Cancer Center

Kalamazoo, Michigan, 49007-3731, United States

Location

CCOP - Duluth

Duluth, Minnesota, 55805, United States

Location

St. John's Regional Health Center

Springfield, Missouri, 65804, United States

Location

CCOP - Montana Cancer Consortium

Billings, Montana, 59101, United States

Location

Deaconess Billings Clinic - Downtown

Billings, Montana, 59107-7000, United States

Location

Good Samaritan Cancer Center at Good Samaritan Hospital

Kearney, Nebraska, 68848-1990, United States

Location

Methodist Cancer Center at Methodist Hospital - Omaha

Omaha, Nebraska, 68114, United States

Location

University Medical Center of Southern Nevada

Las Vegas, Nevada, 89102, United States

Location

CCOP - Nevada Cancer Research Foundation

Las Vegas, Nevada, 89106, United States

Location

Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton

Marlton, New Jersey, 08053, United States

Location

Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare

Vineland, New Jersey, 08360, United States

Location

Fox Chase Virtua Health Cancer Program at Virtua West Jersey

Voorhees Township, New Jersey, 08043, United States

Location

Lipson Cancer and Blood Center at Rochester General Hospital

Rochester, New York, 14621, United States

Location

Mission Hospitals - Memorial Campus

Asheville, North Carolina, 28801, United States

Location

Akron City Hospital

Akron, Ohio, 44309-2090, United States

Location

Charles M. Barrett Cancer Center at University Hospital

Cincinnati, Ohio, 45267, United States

Location

Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

Location

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

Salem, Ohio, 44460, United States

Location

Cancer Treatment Center

Wooster, Ohio, 44691, United States

Location

Natalie Warren Bryant Cancer Center at St. Francis Hospital

Tulsa, Oklahoma, 74136, United States

Location

Kimmel Cancer Center at Thomas Jefferson University - Philadelphia

Philadelphia, Pennsylvania, 19107-5541, United States

Location

Allegheny Cancer Center at Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

Reading Hospital and Medical Center

Reading, Pennsylvania, 19612-6052, United States

Location

Guthrie Cancer Center at Guthrie Clinic Sayre

Sayre, Pennsylvania, 18840, United States

Location

Rapid City Regional Hospital

Rapid City, South Dakota, 57701, United States

Location

Latter Day Saints Hospital

Salt Lake City, Utah, 84143, United States

Location

Theda Care Cancer Institute

Appleton, Wisconsin, 54911, United States

Location

St. Vincent Hospital Regional Cancer Center

Green Bay, Wisconsin, 54307-3508, United States

Location

Bay Area Cancer Care Center at Bay Area Medical Center

Marinette, Wisconsin, 54143, United States

Location

Community Memorial Hospital Cancer Care Center

Menomonee Falls, Wisconsin, 53051, United States

Location

University of Wisconcin Cancer Center at Aspirus Wausau Hospital

Wausau, Wisconsin, 54401, United States

Location

Related Publications (1)

• 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.

  PMID: 15234047 RESULT

MeSH Terms

Conditions

Central Nervous System Neoplasms; Astrocytoma; Glioma

Interventions

Carmustine; Temozolomide; Radiotherapy; Lomustine

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds; Dacarbazine; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics

Limitations and Caveats

Accrual to the TMZ BCNU arm required an acceptable toxicity profile from a pilot arm. Treatment cessation/reduction for toxicity caused the combination arm to be dropped. Per the protocol, the pilot arms were not included in the Phase III analyses.

Results Point of Contact

• Title: Wendy Seiferheld, M.S.
• Organization: NRG Oncology

seiferheldw@nrgoncology.org

Study Officials

• Susan M. Chang, MD

  University of California, San Francisco

  STUDY CHAIR

• Kurt A. Jaeckle, MD

  Mayo Clinic

  STUDY CHAIR

• Peter Bushunow, MD

  Lipson Cancer and Blood Center at Rochester General Hospital

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: Phase I (sequential) followed by phase III (parallel)

Study Record Dates

• First Submitted: January 28, 2000
• First Posted: January 27, 2003
• Study Start: June 1, 2000
• Primary Completion: February 1, 2015
• Study Completion: May 14, 2018
• Last Updated: September 12, 2019
• Results First Posted: November 13, 2017

Record last verified: 2019-08

Locations

US (92)