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

Primary Purpose

Brain and Central Nervous System Tumors

Status

Completed

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

lomustine

procarbazine hydrochloride

vincristine sulfate

radiation therapy

About this trial

This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring adult oligodendroglioma, adult diffuse astrocytoma, adult pilocytic astrocytoma

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

No Intervention

Experimental

Arm Label

Observation

Radiation therapy

Radiation plus PCV chemotherapy

Arm Description

Observation only.

Radiation therapy only.

Radiation and Procarbazine/CCNU/Vincristine (PCV) chemotherapy

Outcomes

Primary Outcome Measures

Overall Survival

Secondary Outcome Measures

Progression-free Survival

The severe or worse toxicities (>= grade 3) of unfavorable patients

Full Information

NCT ID

NCT00003375

First Posted

November 1, 1999

Last Updated

October 15, 2020

Sponsor

Radiation Therapy Oncology Group

Collaborators

National Cancer Institute (NCI), SWOG Cancer Research Network, North Central Cancer Treatment Group, Eastern Cooperative Oncology Group, NRG Oncology

1. Study Identification

Unique Protocol Identification Number

NCT00003375

Brief Title

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

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 Type

Interventional

2. Study Status

Record Verification Date

May 2018

Overall Recruitment Status

Completed

Study Start Date

October 1998 (undefined)

Primary Completion Date

August 2005 (Actual)

Study Completion Date

May 14, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Radiation Therapy Oncology Group

Collaborators

National Cancer Institute (NCI), SWOG Cancer Research Network, North Central Cancer Treatment Group, Eastern Cooperative Oncology Group, NRG Oncology

4. Oversight

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Brain and Central Nervous System Tumors

Keywords

adult oligodendroglioma, adult diffuse astrocytoma, adult pilocytic astrocytoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

370 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Observation

Arm Type

No Intervention

Arm Description

Observation only.

Arm Title

Radiation therapy

Arm Type

Experimental

Arm Description

Radiation therapy only.

Arm Title

Radiation plus PCV chemotherapy

Arm Type

Experimental

Arm Description

Radiation and Procarbazine/CCNU/Vincristine (PCV) chemotherapy

Intervention Type

Drug

Intervention Name(s)

lomustine

Intervention Type

Drug

Intervention Name(s)

procarbazine hydrochloride

Intervention Type

Drug

Intervention Name(s)

vincristine sulfate

Intervention Type

Radiation

Intervention Name(s)

radiation therapy

Primary Outcome Measure Information:

Title

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 Measure Information:

Title

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.

Title

The severe or worse toxicities (>= grade 3) of unfavorable patients

Time Frame

From start of treatment to end of follow-up

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

120 Years

Accepts Healthy Volunteers

Eligibility Criteria

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Edward G. Shaw, MD

Organizational Affiliation

Wake Forest University Health Sciences

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Geoffrey R. Barger, MD

Organizational Affiliation

Barbara Ann Karmanos Cancer Institute

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Jan C. Buckner, MD

Organizational Affiliation

Mayo Clinic

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Minesh P. Mehta, MD

Organizational Affiliation

University of Wisconsin, Madison

Official's Role

Study Chair

12. IPD Sharing Statement

Citations:

PubMed Identifier

24419119

Citation

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.

Results Reference

result

PubMed Identifier

22851558

Citation

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.

Results Reference

result

PubMed Identifier

18976072

Citation

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.

Results Reference

result

Citation

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.

Results Reference

result

Citation

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.

Results Reference

result

PubMed Identifier

32706640

Citation

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.

Results Reference

derived

PubMed Identifier

27050206

Citation

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.

Results Reference

derived

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

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