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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Southwest Oncology Group
North Central Cancer Treatment Group
Eastern Cooperative Oncology Group
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00003375
First received: November 1, 1999
Last updated: November 27, 2013
Last verified: November 2013
  Purpose

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 Intervention Phase
Brain and Central Nervous System Tumors
Drug: lomustine
Drug: procarbazine hydrochloride
Drug: vincristine sulfate
Radiation: radiation therapy
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
  • The severe or worse toxicities (>= grade 3) of unfavorable patients [ Time Frame: From start of treatment to end of follow-up ] [ Designated as safety issue: Yes ]

Enrollment: 370
Study Start Date: October 1998
Primary Completion Date: August 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003375

Sponsors and Collaborators
Radiation Therapy Oncology Group
Southwest Oncology Group
North Central Cancer Treatment Group
Eastern Cooperative Oncology Group
Investigators
Study Chair: Edward G. Shaw, MD Comprehensive Cancer Center of Wake Forest University
Study Chair: Geoffrey R. Barger, MD Barbara Ann Karmanos Cancer Institute
Study Chair: Jan C. Buckner, MD Mayo Clinic
Study Chair: Minesh P. Mehta, MD University of Wisconsin, Madison
  More Information

Additional Information:
Publications:
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.
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.

Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00003375     History of Changes
Other Study ID Numbers: RTOG-9802, CDR0000066367, E-R9802, NCCTG-R9802, SWOG-R9802, RTOG-DEV-1012
Study First Received: November 1, 1999
Last Updated: November 27, 2013
Health Authority: United States: Federal Government

Keywords provided by Radiation Therapy Oncology Group:
adult oligodendroglioma
adult diffuse astrocytoma
adult pilocytic astrocytoma

Additional relevant MeSH terms:
Glioma
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases
Lomustine
Procarbazine
Vincristine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on July 29, 2014