Expired Study
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Vacaville, California 95687


Purpose:

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.


Study summary:

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.


Criteria:

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


Study is Available At:


Original ID:

RTOG-9813


NCT ID:

NCT00004259


Secondary ID:

CDR0000067512


Study Acronym:


Brief Title:

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


Official Title:

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)


Overall Status:

Completed


Study Phase:

Phase 3


Genders:

N/A


Minimum Age:

18 Years


Maximum Age:

120 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

Radiation Therapy Oncology Group


Oversight Authority:

United States: Food and Drug Administration


Reasons Why Stopped:


Study Type:

Interventional


Study Design:


Number of Arms:

4


Number of Groups:

0


Total Enrollment:

230


Enrollment Type:

Actual


Overall Contact Information

Official Name:Susan M. Chang, MD
Study Chair
University of California, San Francisco

Study Dates

Start Date:June 2000
Completion Date:May 14, 2018
Completion Type:Actual
Primary Completion Date:February 1, 2015
Primary Completion Type:Actual
Verification Date:August 2019
Last Changed Date:August 28, 2019
First Received Date:January 28, 2000
First Results Date:May 25, 2017

Study Outcomes

Outcome Type:Secondary Outcome
Measure:(Phase III) Progression-free Survival by MGMT Status
Time Frame:From randomization to date of death. Patients are followed until death. Analysis occurs after 155 de
Safety Issues:False
Description:Progression is defined as a radiographic increase in size of the lesion by > 25%, recurrence of the study lesion, or the development of new lesions, confirmed by imaging. Progression-free survival time is defined as time from randomization to date of p
Outcome Type:Secondary Outcome
Measure:(Phase III) Survival Time by MGMT Status
Time Frame:From randomization to date of death. Patients are followed until death. Analysis occurs after 155 de
Safety Issues:False
Description: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. Tumor tissue samples were analyzed for methylation s
Outcome Type:Secondary Outcome
Measure:(Phase III) Number of Patients With Grade 3 or Higher Toxicity
Time Frame:From randomization to date of death. Patients are followed until death. Analysis occurs after 155 de
Safety Issues:False
Description:Adverse events were graded using CTCAE v2.0. Grade refers to the severity of the 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,
Outcome Type:Secondary Outcome
Measure:(Phase III) Time to Tumor Progression (TTP)
Time Frame:From randomization to date of death. Patients are followed until death. Analysis occurs after 155 de
Safety Issues:False
Description:Three-year rate is reported. Progression is defined as a radiographic increase in size of the lesion by > 25%, recurrence of the study lesion, or the development of new lesions, confirmed by imaging. Time to tumor progression was estimated using the cu
Outcome Type:Primary Outcome
Measure:(Phase I) Number of Subjects With Dose Limiting Toxicities (DLT) on the Two Pilot Arms
Time Frame:From start of treatment to 3 months
Safety Issues:False
Description: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, Grad
Outcome Type:Primary Outcome
Measure:(Phase III) Overall Survival (OS)
Time Frame:From randomization to date of death. Patients are followed until death. Analysis occurs after 155 de
Safety Issues:False
Description: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 i

Study Interventions

Intervention Type:Drug
Name:BCNU 80mg/m2
Description: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).
Arm Name:RT + BCNU/CCNU
Intervention Type:Drug
Name:TMZ 200mg/m2
Description:200 mg/m2 orally on days 1-5 of the first week of radiotherapy. Repeat every 28 days for a total of 12 cycles.
Arm Name:Radiation therapy + temozolomide (TMZ)
Intervention Type:Radiation
Name:radiation therapy
Description:1.8 Gy fractions (to isocenter), 1 fraction per day, 5 days per week to a dose of 59.4 Gy in 33 fractions.
Arm Name:Radiation therapy + temozolomide (TMZ)
Intervention Type:Drug
Name:CCNU
Description: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.
Arm Name:RT + BCNU/CCNU
Intervention Type:Drug
Name:BCNU 150mg/m2
Description: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).
Arm Name:Pilot Arm #2: RT+TMZ+BCNU
Intervention Type:Drug
Name:BCNU 200mg/m2
Description: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).
Arm Name:Pilot Arm #1: RT+TMZ+BCNU
Intervention Type:Drug
Name:TMZ 150mg/m2 six 6-week cycles
Description:150 mg/m2 orally on days 1-5 of the first week of radiotherapy. Repeat for a total of six 6-week cycles
Arm Name:Pilot Arm #1: RT+TMZ+BCNU
Intervention Type:Drug
Name:TMZ 150mg/m2 six 8-week cycles
Description:150 mg/m2 orally on days 1-5 of the first week of radiotherapy. Repeat for a total of six 8-week cycles
Arm Name:Pilot Arm #2: RT+TMZ+BCNU

Study Arms

Study Arm Type:Experimental
Arm Name:Radiation therapy + temozolomide (TMZ)
Description:Radiation therapy (RT) for 6 weeks concurrent with and followed by TMZ 200mg/m2 for twelve 28-day cycles
Study Arm Type:Active Comparator
Arm Name:RT + BCNU/CCNU
Description:Radiation therapy for 6 weeks concurrent with and followed by BCNU 80mg/m2 or CCNU 130 mg/m2 for six 8-week cycles
Study Arm Type:Experimental
Arm Name:Pilot Arm #1: RT+TMZ+BCNU
Description:Radiation therapy for 6 weeks concurrent with and followed by BCNU 200mg/m2 and TMZ 150mg/m2 six 6-week cycles
Study Arm Type:Experimental
Arm Name:Pilot Arm #2: RT+TMZ+BCNU
Description:Radiation therapy for 6 weeks concurrent with and followed by BCNU 150mg/m2 and TMZ 150mg/m2 six 8-week cycles

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:Radiation Therapy Oncology Group
Agency Class:NIH
Agency Type:Collaborator
Agency Name:National Cancer Institute (NCI)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Results Reference
Citation: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.
PMID:15234047

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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