Radiation Therapy With or Without Chemotherapy in Treating Patients With Anaplastic Oligodendroglioma

Brain and Central Nervous System Tumors Clinical Trial

Official title:

Phase III Intergroup Randomized Comparison of Radiation Alone vs. Pre-Radiation Chemotherapy for Pure and Mixed Anaplastic Oligodendrogliomas

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002569
• Other study ID #: RTOG-9402
• Secondary ID: CDR0000063603CAN
• Status: Completed
• Phase: Phase 3
• Start date: July 1994
• Est. completion date: May 21, 2018

Study information

• Verified date: June 2018
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy with radiation therapy may kill more tumor cells.

PURPOSE: Randomized phase III trial to compare the effectiveness of radiation therapy with or without chemotherapy in treating patients who have anaplastic oligodendroglioma.

Description:

OBJECTIVES:

• Compare the overall survival and time to tumor progression in patients with unifocal or multifocal, supratentorial, pure or mixed anaplastic oligodendroglioma treated with radiotherapy with or without procarbazine, lomustine, and vincristine (PCV).

• Compare the toxic effects of these 2 regimens in these patients.

• Compare the quality of life and neurologic function of patients treated with these 2 regimens.

OUTLINE: This is a randomized study. Patients are stratified by age (under 50 vs 50 and over), Karnofsky performance status (60-70% vs 80-100%), and tumor grade (moderately vs highly anaplastic). Within 8 weeks after diagnostic surgery, patients are randomized to 1 of 2 treatment arms.

• Arm I: Within 2 weeks after randomization, patients receive oral lomustine on day 1, oral procarbazine on days 8-21, and vincristine IV on days 8 and 29 (PCV). Treatment continues every 6 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Beginning within 6 weeks after day 29 of course 4, patients undergo radiotherapy 5 days a week for 5.6 weeks followed by boost radiotherapy 5 days a week for 1 week.

• Arm II: Within 2 weeks after randomization, patients undergo radiotherapy as in arm I.

Quality of life is assessed at baseline; at time of CT or MRI scans during study; and every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter after completion of study therapy.

Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 292 patients (146 per arm) will be accrued for this study within 5.4 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 299
• Est. completion date: May 21, 2018
• Est. primary completion date: February 2005
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically proven unifocal or multifocal, supratentorial, pure or mixed anaplastic oligodendroglioma

• Prior suspected or proven low-grade glioma allowed if current histologic proof of pure or mixed anaplastic oligodendroglioma

• Tumor must contain an unequivocal (at least 25%) oligodendroglial element and have 2 or more anaplastic features, 1 of which must be frequent mitoses or endothelial proliferation

• For mixed tumors, the non-oligodendroglial element must be astrocytic and the oligodendroglial or astroglial component may be anaplastic

• No evidence of spinal drop metastasis or spread to noncontiguous meninges

• MRI of spine not required for asymptomatic patients and patients not excluded based on pathologic evidence of local meningeal infiltration by underlying tumor

• No tumor that is predominantly located in the posterior fossa (i.e., brainstem or cerebellum)

• No spinal cord tumors

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• Not specified

Hematopoietic:

• Absolute granulocyte count at least 1,500/mm^3

• Platelet count at least 150,000/mm^3

Hepatic:

• Bilirubin no greater than 2 times normal

• Serum glutamate oxaloacetate transaminase (SGOT) no greater than 2 times normal

• Alkaline phosphatase no greater than 2 times normal

Renal:

• Creatinine no greater than 1.5 times normal

Pulmonary:

• No chronic lung disease unless diffusion capacity of lung for carbon monoxide (DLCO) is at least 60% predicted

Other:

• No active infection

• No other malignancy within the past 5 years except nonmelanomatous skin cancer or carcinoma in situ of the cervix

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• No concurrent steroids as antiemetics

• Concurrent steroids allowed to control central nervous system (CNS) symptoms due to tumor-associated or radiotherapy-associated cerebral edema

Radiotherapy:

• No prior radiotherapy to brain or head/neck

Surgery:

• Prior surgery allowed

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Nervous System Neoplasms
• Oligodendroglioma

Intervention

Drug:
• lomustine

• procarbazine hydrochloride

• vincristine sulfate

Radiation:
• radiation therapy

Locations

Country	Name	City	State
United States	Veterans Affairs Medical Center - Albany	Albany	New York
United States	MBCCOP - University of New Mexico HSC	Albuquerque	New Mexico
United States	Veterans Affairs Medical Center - Albuquerque	Albuquerque	New Mexico
United States	CCOP - Ann Arbor Regional	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Veterans Affairs Medical Center - Ann Arbor	Ann Arbor	Michigan
United States	CCOP - Atlanta Regional	Atlanta	Georgia
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Veterans Affairs Medical Center - Biloxi	Biloxi	Mississippi
United States	Boston Medical Center	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Veterans Affairs Medical Center - Charleston	Charleston	South Carolina
United States	MBCCOP - University of Illinois at Chicago	Chicago	Illinois
United States	Veterans Affairs Medical Center - Chicago (Westside Hospital)	Chicago	Illinois
United States	Barrett Cancer Center, The University Hospital	Cincinnati	Ohio
United States	Veterans Affairs Medical Center - Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	CCOP - Columbus	Columbus	Ohio
United States	Veterans Affairs Medical Center - Dayton	Dayton	Ohio
United States	CCOP - Central Illinois	Decatur	Illinois
United States	University of Colorado Cancer Center	Denver	Colorado
United States	Veterans Affairs Medical Center - Denver	Denver	Colorado
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	Veterans Affairs Medical Center - Detroit	Detroit	Michigan
United States	Cancer Center and Beckman Research Institute, City of Hope	Duarte	California
United States	CCOP - Duluth	Duluth	Minnesota
United States	Dwight David Eisenhower Army Medical Center	Fort Gordon	Georgia
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	University of Texas Medical Branch	Galveston	Texas
United States	CCOP - Greenville	Greenville	South Carolina
United States	Veterans Affairs Medical Center - Hines (Hines Junior VA Hospital)	Hines	Illinois
United States	Cancer Research Center of Hawaii	Honolulu	Hawaii
United States	Tripler Army Medical Center	Honolulu	Hawaii
United States	Veterans Affairs Medical Center - Houston	Houston	Texas
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Veterans Affairs Medical Center - Jackson	Jackson	Mississippi
United States	Veterans Affairs Medical Center - Boston (Jamaica Plain)	Jamaica Plain	Massachusetts
United States	CCOP - Kansas City	Kansas City	Missouri
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Veterans Affairs Medical Center - Kansas City	Kansas City	Missouri
United States	Keesler Medical Center - Keesler AFB	Keesler Air Force Base	Mississippi
United States	CCOP - Dayton	Kettering	Ohio
United States	Albert B. Chandler Medical Center, University of Kentucky	Lexington	Kentucky
United States	Veterans Affairs Medical Center - Lexington	Lexington	Kentucky
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Veterans Affairs Medical Center - Little Rock (McClellan)	Little Rock	Arkansas
United States	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	Veterans Affairs Medical Center - West Los Angeles	Los Angeles	California
United States	Texas Tech University Health Science Center	Lubbock	Texas
United States	Veterans Affairs Outpatient Clinic - Martinez	Martinez	California
United States	Loyola University Medical Center	Maywood	Illinois
United States	MBCCOP - Gulf Coast	Mobile	Alabama
United States	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana
United States	Tulane University School of Medicine	New Orleans	Louisiana
United States	Herbert Irving Comprehensive Cancer Center	New York	New York
United States	CCOP - Bay Area Tumor Institute	Oakland	California
United States	Oklahoma Medical Research Foundation	Oklahoma City	Oklahoma
United States	Veterans Affairs Medical Center - Oklahoma City	Oklahoma City	Oklahoma
United States	Chao Family Comprehensive Cancer Center	Orange	California
United States	CCOP - Greater Phoenix	Phoenix	Arizona
United States	Veterans Affairs Medical Center - Phoenix (Carl T. Hayden)	Phoenix	Arizona
United States	CCOP - Columbia River Program	Portland	Oregon
United States	OHSU Cancer Institute	Portland	Oregon
United States	Veterans Affairs Medical Center - Portland	Portland	Oregon
United States	University of Rochester Medical Center	Rochester	New York
United States	University of California Davis Medical Center	Sacramento	California
United States	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri
United States	St. Louis University Health Sciences Center	Saint Louis	Missouri
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	Veterans Affairs Medical Center - Salt Lake City	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Veterans Affairs Medical Center - San Antonio (Murphy)	San Antonio	Texas
United States	UCSF Cancer Center and Cancer Research Institute	San Francisco	California
United States	CCOP - Santa Rosa Memorial Hospital	Santa Rosa	California
United States	CCOP - Virginia Mason Research Center	Seattle	Washington
United States	Swedish Cancer Institute	Seattle	Washington
United States	Veterans Affairs Medical Center - Seattle	Seattle	Washington
United States	Louisiana State University Health Sciences Center - Shreveport	Shreveport	Louisiana
United States	Veterans Affairs Medical Center - Shreveport	Shreveport	Louisiana
United States	Providence Hospital - Southfield	Southfield	Michigan
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	CCOP - Cancer Research for the Ozarks	Springfield	Missouri
United States	CCOP - Northwest	Tacoma	Washington
United States	Madigan Army Medical Center	Tacoma	Washington
United States	CCOP - Scott and White Hospital	Temple	Texas
United States	Veterans Affairs Medical Center - Temple	Temple	Texas
United States	CCOP - Toledo Community Hospital Oncology Program	Toledo	Ohio
United States	David Grant Medical Center	Travis Air Force Base	California
United States	Arizona Cancer Center	Tucson	Arizona
United States	Veterans Affairs Medical Center - Tucson	Tucson	Arizona
United States	CCOP - Wichita	Wichita	Kansas
United States	Veterans Affairs Medical Center - Wichita	Wichita	Kansas
United States	CCOP - Southeast Cancer Control Consortium	Winston-Salem	North Carolina

Sponsors (6)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	Eastern Cooperative Oncology Group, National Cancer Institute (NCI), NCIC Clinical Trials Group, North Central Cancer Treatment Group, Southwest Oncology Group

Country where clinical trial is conducted

United States, 

References & Publications (7)

Cairncross G, Seiferheld W, Shaw E, et al.: An intergroup randomized controlled clinical trial (RCT) of chemotherapy plus radiation (RT) versus RT alone for pure and mixed anaplastic oligodendrogliomas: initial report of RTOG 94-02. [Abstract] J Clin Onco

Cairncross JG, Wang M, Shaw EG, et al.: Chemotherapy plus radiotherapy (CT-RT) versus RT alone for patients with anaplastic oligodendroglioma: long-term results of the RTOG 9402 phase III study. [Abstract] J Clin Oncol 30 (Suppl 15): A-2008b, 2012.

Giannini C, Burger PC, Berkey BA, Cairncross JG, Jenkins RB, Mehta M, Curran WJ, Aldape K. Anaplastic oligodendroglial tumors: refining the correlation among histopathology, 1p 19q deletion and clinical outcome in Intergroup Radiation Therapy Oncology Gro — View Citation

Intergroup Radiation Therapy Oncology Group Trial 9402, Cairncross G, Berkey B, Shaw E, Jenkins R, Scheithauer B, Brachman D, Buckner J, Fink K, Souhami L, Laperierre N, Mehta M, Curran W. Phase III trial of chemotherapy plus radiotherapy compared with ra — View Citation

Jenkins RB, Curran W, Scott CB, Cairncross G. Pilot evaluation of 1p and 19q deletions in anaplastic oligodendrogliomas collected by a national cooperative cancer treatment group. Am J Clin Oncol. 2001 Oct;24(5):506-8. — View Citation

Shaw EG, Seiferheld W, Cairncross JG, et al.: Radiation therapy (RT) alone vs intensive procarbazine-CCNU-vincristine (I-PCV) chemotherapy followed by radiation therapy for anaplastic oligodendroglioma (AO) and mixed oligo-astrocytoma (MOA): results of Ra

Wang M, Cairncross G, Shaw E, Jenkins R, Scheithauer B, Brachman D, Buckner J, Fink K, Souhami L, Laperriere N, Mehta M, Curran W; Radiation Therapy Oncology Group (RTOG); North Central Cancer Treatment Group (NCCTG); Southwest Oncology Group (SWOG); Nati — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival		From randomization to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 3 years.
Secondary	Time to tumor progression		From randomization to date of progression or last follow-up. Analysis occurs after all patients have been potentially followed for 3 years.
Secondary	Frequency of severe (>= Grade 3) toxicities		From randomization to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 3 years.