Observation or Radiation Therapy With or Without Combination Chemotherapy in Treating Patients With Low-Grade Glioma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT00003375

Recruitment Status : Completed

First Posted : January 27, 2003

Last Update Posted : October 19, 2020

View this study on the modernized ClinicalTrials.gov

Sponsor:

Collaborators:

National Cancer Institute (NCI)

SWOG Cancer Research Network

North Central Cancer Treatment Group

Eastern Cooperative Oncology Group

NRG Oncology

Information provided by (Responsible Party):

Radiation Therapy Oncology Group

Study Description

Brief Summary:

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether radiation therapy combined with chemotherapy is more effective than radiation therapy alone in treating patients with low-grade glioma.

PURPOSE: Phase II/III trial to evaluate observation and to compare the effectiveness of radiation therapy with or without combination chemotherapy in treating patients with low-grade glioma.

Condition or disease	Intervention/treatment	Phase
Brain and Central Nervous System Tumors	Drug: lomustine Drug: procarbazine hydrochloride Drug: vincristine sulfate Radiation: radiation therapy	Phase 2 Phase 3

Detailed Description:

OBJECTIVES:

Identify the overall survival of low-risk adult patients with supratentorial low-grade glioma who are observed postoperatively.
Compare the overall survival of high-risk adult patients with supratentorial low-grade glioma who receive postoperative external beam radiotherapy with or without procarbazine, lomustine, and vincristine (PCV) chemotherapy.
Compare the toxic effects of postoperative radiotherapy with or without PCV chemotherapy in patients with unfavorable low-grade glioma.

OUTLINE: This is a randomized study. Patients are stratified according to tumor subtype (astrocytoma [mixed-astro dominant or equal astro/oligo mix] vs oligodendroglioma [mixed-oligo dominant]), age (younger than 40 vs at least 40), Karnofsky performance status (60-80% vs 90-100%), and contrast enhancement on preoperative scan (present vs absent). Patients with low-risk disease (younger than 40 years old whose tumors have been surgically removed) are assigned to arm I. Patients with high-risk disease (at least 40 years old or who have had incomplete tumor removal) are randomized to arm II or III.

Arm I (low-risk patients): Patients are observed. Patients may receive treatment if tumor recurs.
Arm II (high-risk patients): Patients receive daily external beam radiotherapy 5 days a week for 6 weeks.
Arm III (high-risk patients): Patients receive radiotherapy as in arm II followed by chemotherapy 1 month later. Chemotherapy consists of oral lomustine on day 1, vincristine IV on days 8 and 29, and oral procarbazine on days 8-21. Each course of chemotherapy lasts 8 weeks. Patients may receive up to 6 courses of chemotherapy.

Patients are followed every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 252 patients will be accrued within 5.25 years.

Study Design

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	370 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase II Study of Observation in Favorable Low-Grade Glioma and a Phase II Study of Radiation With or Without PCV Chemotherapy in Unfavorable Low-Grade Glioma
Study Start Date :	October 1998
Actual Primary Completion Date :	August 2005
Actual Study Completion Date :	May 14, 2018

Resource links provided by the National Library of Medicine

Genetic and Rare Diseases Information Center resources: Glioma Oligodendroglioma Diffuse Astrocytoma Pilocytic Astrocytoma

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
No Intervention: Observation Observation only.
Experimental: Radiation therapy Radiation therapy only.	Radiation: radiation therapy
Experimental: Radiation plus PCV chemotherapy Radiation and Procarbazine/CCNU/Vincristine (PCV) chemotherapy	Drug: lomustine Drug: procarbazine hydrochloride Drug: vincristine sulfate Radiation: radiation therapy

Outcome Measures

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 5 years or 80 deaths have been reported. ]

Secondary Outcome Measures :

Progression-free Survival [ Time Frame: From randomization to the date of progression, death or last follow-up. Analysis ours at the same time as the primary outcome analysis. ]
The severe or worse toxicities (>= grade 3) of unfavorable patients [ Time Frame: From start of treatment to end of follow-up ]

Eligibility Criteria

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Layout table for eligibility information

Ages Eligible for Study:	18 Years to 120 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed unifocal or multifocal supratentorial WHO grade II astrocytoma (diffuse fibrillary, protoplasmic, or gemistocytic), oligodendroglioma, or oligoastrocytoma
Patients with neurofibromatosis are eligible
No other low-grade histologies, including:
- Pilocytic astrocytoma
- Subependymal giant cell astrocytoma of tuberous sclerosis
- Subependymoma
- Pleomorphic xanthoastrocytoma
- Presence of a neuronal element such as ganglioglioma
- Dysneuroembryoplastic epithelial tumor
No presence of any high-grade glioma, including:
- Anaplastic astrocytoma
- Glioblastoma multiforme
- Anaplastic oligodendroglioma
- Anaplastic oligoastrocytoma
No tumors in nonsupratentorial or other locations including optic chiasm, optic nerve(s), pons, medulla, cerebellum, or spinal cord
No evidence of spread to spinal meninges or noncontiguous cranial meninges (i.e., leptomeningeal gliomatosis)
No gliomatosis cerebri

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

Karnofsky 60-100%

Hematopoietic:

For high-risk patients:
- Granulocyte count at least 1,500/mm^3
- Platelet count normal

Hepatic:

Bilirubin no greater than 2 times normal
SGOT or SGPT no greater than 4 times normal
Alkaline phosphatase no greater than 2 times normal

Renal:

Creatinine no greater than 2 times normal

Pulmonary:

No chronic lung disease (unless DLCO at least 60%)

Neurological:

Neurologic function score no greater than 3

Other:

Not pregnant or nursing
Fertile patients must use effective contraception
No other malignancy within the past 5 years except carcinoma in situ of the cervix or nonmelanoma skin cancer
No active infection

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

Chemotherapy:

No prior chemotherapy

Endocrine therapy:

Not specified

Radiotherapy:

No prior radiotherapy to the head or neck (unless brain is clearly excluded, such as radiotherapy for localized vocal cord cancer)

Surgery:

Not specified

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00003375

Sponsors and Collaborators

Radiation Therapy Oncology Group

National Cancer Institute (NCI)

SWOG Cancer Research Network

North Central Cancer Treatment Group

Eastern Cooperative Oncology Group

NRG Oncology

Investigators

Layout table for investigator information

Study Chair:	Edward G. Shaw, MD	Wake Forest University Health Sciences
Study Chair:	Geoffrey R. Barger, MD	Barbara Ann Karmanos Cancer Institute
Study Chair:	Jan C. Buckner, MD	Mayo Clinic
Study Chair:	Minesh P. Mehta, MD	University of Wisconsin, Madison

More Information

Publications of Results:

Prabhu RS, Won M, Shaw EG, Hu C, Brachman DG, Buckner JC, Stelzer KJ, Barger GR, Brown PD, Gilbert MR, Mehta MP. Effect of the addition of chemotherapy to radiotherapy on cognitive function in patients with low-grade glioma: secondary analysis of RTOG 98-02. J Clin Oncol. 2014 Feb 20;32(6):535-41. doi: 10.1200/JCO.2013.53.1830. Epub 2014 Jan 13.

Shaw EG, Wang M, Coons SW, Brachman DG, Buckner JC, Stelzer KJ, Barger GR, Brown PD, Gilbert MR, Mehta MP. Randomized trial of radiation therapy plus procarbazine, lomustine, and vincristine chemotherapy for supratentorial adult low-grade glioma: initial results of RTOG 9802. J Clin Oncol. 2012 Sep 1;30(25):3065-70. doi: 10.1200/JCO.2011.35.8598. Epub 2012 Jul 30.

Shaw EG, Berkey B, Coons SW, Bullard D, Brachman D, Buckner JC, Stelzer KJ, Barger GR, Brown PD, Gilbert MR, Mehta M. Recurrence following neurosurgeon-determined gross-total resection of adult supratentorial low-grade glioma: results of a prospective clinical trial. J Neurosurg. 2008 Nov;109(5):835-41. doi: 10.3171/JNS/2008/109/11/0835.

Shaw EG, Wang S, Coons S, et al.: Final report of Radiation Therapy Oncology Group (RTOG) protocol 9802: radiation therapy (RT) versus RT + procarbazine, CCNU, and vincristine (PCV) chemotherapy for adult low-grade glioma (LGG). [Abstract] J Clin Oncol 26 (Suppl 15): A-2006, 2008.

Shaw EG, Berkey B, Coons SW, et al.: Initial report of Radiation Therapy Oncology Group (RTOG) 9802: prospective studies in adult low-grade glioma (LGG). [Abstract] J Clin Oncol 24 (Suppl 18): A-1500, 2006.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Bell EH, Zhang P, Shaw EG, Buckner JC, Barger GR, Bullard DE, Mehta MP, Gilbert MR, Brown PD, Stelzer KJ, McElroy JP, Fleming JL, Timmers CD, Becker AP, Salavaggione AL, Liu Z, Aldape K, Brachman DG, Gertler SZ, Murtha AD, Schultz CJ, Johnson D, Laack NN, Hunter GK, Crocker IR, Won M, Chakravarti A. Comprehensive Genomic Analysis in NRG Oncology/RTOG 9802: A Phase III Trial of Radiation Versus Radiation Plus Procarbazine, Lomustine (CCNU), and Vincristine in High-Risk Low-Grade Glioma. J Clin Oncol. 2020 Oct 10;38(29):3407-3417. doi: 10.1200/JCO.19.02983. Epub 2020 Jul 24.

Buckner JC, Shaw EG, Pugh SL, Chakravarti A, Gilbert MR, Barger GR, Coons S, Ricci P, Bullard D, Brown PD, Stelzer K, Brachman D, Suh JH, Schultz CJ, Bahary JP, Fisher BJ, Kim H, Murtha AD, Bell EH, Won M, Mehta MP, Curran WJ Jr. Radiation plus Procarbazine, CCNU, and Vincristine in Low-Grade Glioma. N Engl J Med. 2016 Apr 7;374(14):1344-55. doi: 10.1056/NEJMoa1500925.

Layout table for additonal information

Responsible Party:	Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:	NCT00003375
Other Study ID Numbers:	RTOG-9802 CDR0000066367 E-R9802 NCCTG-R9802 SWOG-R9802
First Posted:	January 27, 2003 Key Record Dates
Last Update Posted:	October 19, 2020
Last Verified:	May 2018

Keywords provided by Radiation Therapy Oncology Group:


adult oligodendroglioma adult diffuse astrocytoma adult pilocytic astrocytoma

Additional relevant MeSH terms:

Layout table for MeSH terms

Nervous System Neoplasms Central Nervous System Neoplasms Neoplasms Neoplasms by Site Nervous System Diseases Vincristine Lomustine Procarbazine	Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Alkylating Alkylating Agents

To Top