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

This study has been completed.
Sponsor:
Collaborators:
North Central Cancer Treatment Group
Southwest Oncology Group
Eastern Cooperative Oncology Group
NCIC Clinical Trials Group
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00002569
First received: November 1, 1999
Last updated: September 27, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: lomustine
Drug: procarbazine hydrochloride
Drug: vincristine sulfate
Radiation: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase III Intergroup Randomized Comparison of Radiation Alone vs. Pre-Radiation Chemotherapy for Pure and Mixed Anaplastic Oligodendrogliomas

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: From randomization to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 3 years. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to tumor progression [ Time Frame: From randomization to date of progression or last follow-up. Analysis occurs after all patients have been potentially followed for 3 years. ] [ Designated as safety issue: No ]
  • Frequency of severe (>= Grade 3) toxicities [ Time Frame: From randomization to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 3 years. ] [ Designated as safety issue: Yes ]

Enrollment: 299
Study Start Date: July 1994
Primary Completion Date: February 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).
Drug: lomustine Drug: procarbazine hydrochloride Drug: vincristine sulfate Radiation: radiation therapy

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002569

  Show 95 Study Locations
Sponsors and Collaborators
Radiation Therapy Oncology Group
North Central Cancer Treatment Group
Southwest Oncology Group
Eastern Cooperative Oncology Group
NCIC Clinical Trials Group
Investigators
Study Chair: J. Gregory Cairncross, MD London Regional Cancer Program at London Health Sciences Centre
Study Chair: Steven R. Alberts, MD Mayo Clinic
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
Study Chair: Normand Laperriere, MD, FRCPC Princess Margaret Hospital, Canada
  More Information

Additional Information:
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.
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.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00002569     History of Changes
Other Study ID Numbers: RTOG-9402, CDR0000063603, CAN-NCIC-CE2, E-R9402, NCCTG-927252, SWOG-9402, INT-0149
Study First Received: November 1, 1999
Last Updated: September 27, 2013
Health Authority: United States: Federal Government

Keywords provided by Radiation Therapy Oncology Group:
adult anaplastic oligodendroglioma
adult mixed glioma

Additional relevant MeSH terms:
Nervous System Neoplasms
Oligodendroglioma
Central Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Nervous System Diseases
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Lomustine
Procarbazine
Vincristine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on August 26, 2014