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

Radiation Therapy Oncology Group

Status and phase: Completed; Phase 3; Phase 2

Conditions: Brain and Central Nervous System Tumors

Treatments: Drug: procarbazine hydrochloride; Drug: lomustine; Radiation: radiation therapy; Drug: vincristine sulfate

Study type: Interventional

Funder types: Other; NETWORK; NIH

Identifiers

NCT00003375

SWOG-R9802

CDR0000066367

E-R9802

RTOG-9802

NCCTG-R9802

Details and patient eligibility

About

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.

Full 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.

Enrollment: 370 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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370 participants in 3 patient groups

Observation

No Intervention group

Description:

Observation only.

Radiation therapy

Experimental group

Description:

Radiation therapy only.

Treatment:

Radiation: radiation therapy

Radiation plus PCV chemotherapy

Experimental group

Description:

Radiation and Procarbazine/CCNU/Vincristine (PCV) chemotherapy

Treatment:

Radiation: radiation therapy

Drug: vincristine sulfate

Drug: lomustine

Drug: procarbazine hydrochloride