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

NCT ID: NCT00003375

Last Updated: 2024-07-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 370 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1998-10-31
• Study Completion Date: 2018-05-14

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.

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.

Conditions

Brain and Central Nervous System Tumors

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Observation

Observation only.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Radiation therapy

Radiation therapy only.

Group Type: EXPERIMENTAL

radiation therapy

Intervention Type: RADIATION

Radiation plus PCV chemotherapy

Radiation and Procarbazine/CCNU/Vincristine (PCV) chemotherapy

Group Type: EXPERIMENTAL

lomustine

Intervention Type: DRUG

procarbazine hydrochloride

Intervention Type: DRUG

vincristine sulfate

Intervention Type: DRUG

radiation therapy

Intervention Type: RADIATION

Interventions

lomustine

Intervention Type: DRUG

procarbazine hydrochloride

Intervention Type: DRUG

vincristine sulfate

Intervention Type: DRUG

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

SWOG Cancer Research Network

NETWORK

Sponsor Role: collaborator

North Central Cancer Treatment Group

NETWORK

Sponsor Role: collaborator

Eastern Cooperative Oncology Group

NETWORK

Sponsor Role: collaborator

NRG Oncology

OTHER

Sponsor Role: collaborator

Radiation Therapy Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Edward G. Shaw, MD

Role: STUDY_CHAIR

Wake Forest University Health Sciences

Geoffrey R. Barger, MD

Role: STUDY_CHAIR

Barbara Ann Karmanos Cancer Institute

Jan C. Buckner, MD

Role: STUDY_CHAIR

Mayo Clinic

Minesh P. Mehta, MD

Role: STUDY_CHAIR

University of Wisconsin, Madison

References

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.

Reference Type: RESULT

PMID: 24419119 (View on PubMed)

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.

Reference Type: RESULT

PMID: 22851558 (View on PubMed)

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.

Reference Type: RESULT

PMID: 18976072 (View on PubMed)

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.

Reference Type: RESULT

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.

Reference Type: RESULT

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.

Reference Type: DERIVED

PMID: 32706640 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27050206 (View on PubMed)

Related Links

https://nctn-data-archive.nci.nih.gov/

Related Info

Other Identifiers

CDR0000066367

Identifier Type: -

Identifier Source: secondary_id

E-R9802

Identifier Type: -

Identifier Source: secondary_id

NCCTG-R9802

Identifier Type: -

Identifier Source: secondary_id

SWOG-R9802

Identifier Type: -

Identifier Source: secondary_id

RTOG-9802

Identifier Type: -

Identifier Source: org_study_id