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

Brain and Central Nervous System Tumors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003375
• Other study ID #: RTOG-9802
• Secondary ID: CDR0000066367E-R
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: October 1998
• Est. completion date: May 14, 2018

Study information

• Verified date: May 2018
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 370
• Est. completion date: May 14, 2018
• Est. primary completion date: August 2005
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Nervous System Neoplasms

Intervention

Drug:
• lomustine

• procarbazine hydrochloride

• vincristine sulfate

Radiation:
• radiation therapy

Locations

Country	Name	City	State
n/a

Sponsors (6)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	Eastern Cooperative Oncology Group, National Cancer Institute (NCI), North Central Cancer Treatment Group, NRG Oncology, Southwest Oncology Group

References & Publications (5)

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- — View 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 cli — View 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.

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 — View 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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival		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	Progression-free Survival		From randomization to the date of progression, death or last follow-up. Analysis ours at the same time as the primary outcome analysis.
Secondary	The severe or worse toxicities (>= grade 3) of unfavorable patients		From start of treatment to end of follow-up