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

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

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.

Study Overview

• Status: Completed
• Conditions: Brain and Central Nervous System Tumors
• Intervention / Treatment: Radiation: radiation therapy; Drug: vincristine sulfate; Drug: lomustine; Drug: procarbazine hydrochloride

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 299
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36688
      • MBCCOP - Gulf Coast
  • Arizona
    • Phoenix, Arizona, United States, 85006-2726
      • CCOP - Greater Phoenix
    • Phoenix, Arizona, United States, 85012
      • Veterans Affairs Medical Center - Phoenix (Carl T. Hayden)
    • Tucson, Arizona, United States, 85724
      • Arizona Cancer Center
    • Tucson, Arizona, United States, 85723
      • Veterans Affairs Medical Center - Tucson
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
    • Little Rock, Arkansas, United States, 72205
      • Veterans Affairs Medical Center - Little Rock (McClellan)
  • California
    • Duarte, California, United States, 91010-3000
      • Cancer Center and Beckman Research Institute, City of Hope
    • Los Angeles, California, United States, 90095-1781
      • Jonsson Comprehensive Cancer Center, UCLA
    • Los Angeles, California, United States, 90033-0804
      • USC/Norris Comprehensive Cancer Center and Hospital
    • Los Angeles, California, United States, 90073
      • Veterans Affairs Medical Center - West Los Angeles
    • Martinez, California, United States, 94553
      • Veterans Affairs Outpatient Clinic - Martinez
    • Oakland, California, United States, 94609-3305
      • CCOP - Bay Area Tumor Institute
    • Orange, California, United States, 92868
      • Chao Family Comprehensive Cancer Center
    • Sacramento, California, United States, 95817
      • University of California Davis Medical Center
    • San Francisco, California, United States, 94143-0128
      • UCSF Cancer Center and Cancer Research Institute
    • Santa Rosa, California, United States, 95403
      • CCOP - Santa Rosa Memorial Hospital
    • Travis Air Force Base, California, United States, 94535
      • David Grant Medical Center
  • Colorado
    • Denver, Colorado, United States, 80220
      • Veterans Affairs Medical Center - Denver
    • Denver, Colorado, United States, 80010
      • University of Colorado Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30342-1701
      • CCOP - Atlanta Regional
    • Fort Gordon, Georgia, United States, 30905-5650
      • Dwight David Eisenhower Army Medical Center
  • Hawaii
    • Honolulu, Hawaii, United States, 96859-5000
      • Tripler Army Medical Center
    • Honolulu, Hawaii, United States, 96813-2424
      • Cancer Research Center of Hawaii
  • Illinois
    • Chicago, Illinois, United States, 60612-7323
      • MBCCOP - University of Illinois at Chicago
    • Chicago, Illinois, United States, 60612
      • Veterans Affairs Medical Center - Chicago (Westside Hospital)
    • Decatur, Illinois, United States, 62526
      • CCOP - Central Illinois
    • Hines, Illinois, United States, 60141
      • Veterans Affairs Medical Center - Hines (Hines Junior VA Hospital)
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Kansas
    • Kansas City, Kansas, United States, 66160-7353
      • University of Kansas Medical Center
    • Wichita, Kansas, United States, 67214-3882
      • CCOP - Wichita
    • Wichita, Kansas, United States, 67218
      • Veterans Affairs Medical Center - Wichita
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0084
      • Albert B. Chandler Medical Center, University of Kentucky
    • Lexington, Kentucky, United States, 40502-2236
      • Veterans Affairs Medical Center - Lexington
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University School of Medicine
    • New Orleans, Louisiana, United States, 70112
      • MBCCOP - LSU Health Sciences Center
    • Shreveport, Louisiana, United States, 71130-3932
      • Louisiana State University Health Sciences Center - Shreveport
    • Shreveport, Louisiana, United States, 71130
      • Veterans Affairs Medical Center - Shreveport
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
    • Jamaica Plain, Massachusetts, United States, 02130
      • Veterans Affairs Medical Center - Boston (Jamaica Plain)
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • Veterans Affairs Medical Center - Ann Arbor
    • Ann Arbor, Michigan, United States, 48106
      • CCOP - Ann Arbor Regional
    • Ann Arbor, Michigan, United States, 48109-0912
      • University of Michigan Comprehensive Cancer Center
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Detroit, Michigan, United States, 48201-1379
      • Barbara Ann Karmanos Cancer Institute
    • Detroit, Michigan, United States, 48201-1932
      • Veterans Affairs Medical Center - Detroit
    • Southfield, Michigan, United States, 48075-9975
      • Providence Hospital - Southfield
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • CCOP - Duluth
  • Mississippi
    • Biloxi, Mississippi, United States, 39531-2410
      • Veterans Affairs Medical Center - Biloxi
    • Jackson, Mississippi, United States, 39216-4505
      • University of Mississippi Medical Center
    • Jackson, Mississippi, United States, 39216
      • Veterans Affairs Medical Center - Jackson
    • Keesler Air Force Base, Mississippi, United States, 39534-2576
      • Keesler Medical Center - Keesler AFB
  • Missouri
    • Kansas City, Missouri, United States, 64128
      • Veterans Affairs Medical Center - Kansas City
    • Kansas City, Missouri, United States, 64131
      • CCOP - Kansas City
    • Saint Louis, Missouri, United States, 63141
      • CCOP - St. Louis-Cape Girardeau
    • Saint Louis, Missouri, United States, 63110
      • St. Louis University Health Sciences Center
    • Springfield, Missouri, United States, 65807
      • CCOP - Cancer Research for the Ozarks
  • Montana
    • Billings, Montana, United States, 59101
      • CCOP - Montana Cancer Consortium
  • New Mexico
    • Albuquerque, New Mexico, United States, 87108-5138
      • Veterans Affairs Medical Center - Albuquerque
    • Albuquerque, New Mexico, United States, 87131
      • MBCCOP - University of New Mexico HSC
  • New York
    • Albany, New York, United States, 12208
      • Veterans Affairs Medical Center - Albany
    • New York, New York, United States, 10032
      • Herbert Irving Comprehensive Cancer Center
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27104-4241
      • CCOP - Southeast Cancer Control Consortium
  • Ohio
    • Cincinnati, Ohio, United States, 45220-2288
      • Veterans Affairs Medical Center - Cincinnati
    • Cincinnati, Ohio, United States, 45267-0501
      • Barrett Cancer Center, The University Hospital
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center
    • Columbus, Ohio, United States, 43206
      • CCOP - Columbus
    • Dayton, Ohio, United States, 45428
      • Veterans Affairs Medical Center - Dayton
    • Kettering, Ohio, United States, 45429
      • CCOP - Dayton
    • Toledo, Ohio, United States, 43623-3456
      • CCOP - Toledo Community Hospital Oncology Program
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma Medical Research Foundation
    • Oklahoma City, Oklahoma, United States, 73104
      • Veterans Affairs Medical Center - Oklahoma City
  • Oregon
    • Portland, Oregon, United States, 97207
      • Veterans Affairs Medical Center - Portland
    • Portland, Oregon, United States, 97225
      • CCOP - Columbia River Program
    • Portland, Oregon, United States, 97239
      • OHSU Cancer Institute
  • South Carolina
    • Charleston, South Carolina, United States, 29425-0721
      • Medical University of South Carolina
    • Charleston, South Carolina, United States, 29401-5799
      • Veterans Affairs Medical Center - Charleston
    • Greenville, South Carolina, United States, 29615
      • CCOP - Greenville
    • Spartanburg, South Carolina, United States, 29303
      • CCOP - Upstate Carolina
  • Texas
    • Fort Sam Houston, Texas, United States, 78234-6200
      • Brooke Army Medical Center
    • Galveston, Texas, United States, 77555-0565
      • University of Texas Medical Branch
    • Houston, Texas, United States, 77030
      • Veterans Affairs Medical Center - Houston
    • Lubbock, Texas, United States, 79415
      • Texas Tech University Health Science Center
    • San Antonio, Texas, United States, 78284
      • Veterans Affairs Medical Center - San Antonio (Murphy)
    • San Antonio, Texas, United States, 78284-7845
      • University of Texas Health Science Center at San Antonio
    • Temple, Texas, United States, 76504
      • Veterans Affairs Medical Center - Temple
    • Temple, Texas, United States, 76508
      • CCOP - Scott and White Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84148
      • Veterans Affairs Medical Center - Salt Lake City
    • Salt Lake City, Utah, United States, 84112-5550
      • Huntsman Cancer Institute
  • Washington
    • Seattle, Washington, United States, 98101
      • CCOP - Virginia Mason Research Center
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute
    • Seattle, Washington, United States, 98108
      • Veterans Affairs Medical Center - Seattle
    • Tacoma, Washington, United States, 98405-0986
      • CCOP - Northwest
    • Tacoma, Washington, United States, 98431-5048
      • Madigan Army Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Radiation therapy (RT) alone; Radiation therapy (RT) alone - External Beam RT 59.4 Gy (1.8 Gy x 33 fractions, 5 days a week) to MR defined tumor volume.	Radiation: radiation therapy
Experimental: Intensive pre-treatment chemotherapy and radiation therapy; Intensive pre-treatment chemotherapy (Day 1 CCNU 130 mg/m2 p.o., Day 8 - Vincristine 1.4 mg/m2 i.v., Days 8-21 - Procarbazine 75 mg/m2 p.o., Day 29 - Vincristine 1.4 mg/m2 i.v.) followed by radiation therapy (External Beam RT 59.4 Gy (1.8 Gy x 33 fractions, 5 days a week) to MR defined tumor volume).	Radiation: radiation therapy; Drug: vincristine sulfate; Drug: lomustine; Drug: procarbazine hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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.
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.

Collaborators and Investigators

• Sponsor: Radiation Therapy Oncology Group
• Collaborators: National Cancer Institute (NCI); Eastern Cooperative Oncology Group; NCIC Clinical Trials Group; Southwest Oncology Group; North Central Cancer Treatment Group
• Investigators: Study Chair: Normand Laperriere, MD, FRCPC, Princess Margaret Hospital, Canada; Study Chair: J. Gregory Cairncross, MD, London Health Sciences Centre; Study Chair: Karen L. Fink, MD, PhD, Simmons Cancer Center; Study Chair: Richard M. Hellman, MD, Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center

Publications and helpful links

General Publications

• 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.
• 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); National Cancer Institute of Canada Clinical Trials Group (NCIC CTG); Eastern Cooperative Oncology Group (ECOG). Cognition and quality of life after chemotherapy plus radiotherapy (RT) vs. RT for pure and mixed anaplastic oligodendrogliomas: radiation therapy oncology group trial 9402. Int J Radiat Oncol Biol Phys. 2010 Jul 1;77(3):662-9. doi: 10.1016/j.ijrobp.2009.06.004. Epub 2009 Sep 23.
• 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 Group Trial 9402. Brain Pathol. 2008 Jul;18(3):360-9. doi: 10.1111/j.1750-3639.2008.00129.x. Epub 2008 Mar 26.
• 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 radiotherapy alone for pure and mixed anaplastic oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402. J Clin Oncol. 2006 Jun 20;24(18):2707-14. doi: 10.1200/JCO.2005.04.3414.
• 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 Oncol 22 (Suppl 14): A-1500, 107s, 2004.
• 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 Radiation Therapy Oncology Group (RTOG) - intergroup protocol 94-02. [Abstract] Int J Radiat Oncol Biol Phys 60 (1 Suppl 1): A-57, S163, 2004.
• 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. doi: 10.1097/00000421-200110000-00018.
• Lassman AB, Hoang-Xuan K, Polley MC, Brandes AA, Cairncross JG, Kros JM, Ashby LS, Taphoorn MJB, Souhami L, Dinjens WNM, Laack NN, Kouwenhoven MCM, Fink KL, French PJ, Macdonald DR, Lacombe D, Won M, Gorlia T, Mehta MP, van den Bent MJ. Joint Final Report of EORTC 26951 and RTOG 9402: Phase III Trials With Procarbazine, Lomustine, and Vincristine Chemotherapy for Anaplastic Oligodendroglial Tumors. J Clin Oncol. 2022 Aug 10;40(23):2539-2545. doi: 10.1200/JCO.21.02543. Epub 2022 Jun 22.
• Cairncross G, Wang M, Shaw E, Jenkins R, Brachman D, Buckner J, Fink K, Souhami L, Laperriere N, Curran W, Mehta M. Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. J Clin Oncol. 2013 Jan 20;31(3):337-43. doi: 10.1200/JCO.2012.43.2674. Epub 2012 Oct 15.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 1994
• Primary Completion (Actual): February 1, 2005
• Study Completion (Actual): May 21, 2018

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Actual): June 18, 2018
• Last Update Submitted That Met QC Criteria: June 15, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: adult anaplastic oligodendroglioma; adult mixed glioma
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Central Nervous System Neoplasms; Oligodendroglioma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Phytogenic; Vincristine; Lomustine; Procarbazine
• Other Study ID Numbers: RTOG-9402; CDR0000063603; CAN-NCIC-CE2; E-R9402; NCCTG-927252; SWOG-9402; INT-0149