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

Sponsor

Radiation Therapy Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT00003375

Collaborator

National Cancer Institute (NCI) (NIH), Southwest Oncology Group (Other), North Central Cancer Treatment Group (Other), Eastern Cooperative Oncology Group (Other), NRG Oncology (Other)

370

Enrollment

Arms

235.4

Duration (Months)

Study Details

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

Study Type:

Interventional

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 :

Oct 1, 1998

Actual Primary Completion Date :

Aug 1, 2005

Actual Study Completion Date :

May 14, 2018

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

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 [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 [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 [From start of treatment to end of follow-up]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts 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