Radiation Therapy With or Without Temozolomide in Treating Patients With Low-Grade Glioma - Full Text View

Sponsor:	Eastern Cooperative Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00978458

Purpose

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether radiation therapy is more effective when given together with or without temozolomide in treating patients with low-grade glioma.

PURPOSE: This randomized phase III trial is studying radiation therapy so see how well it works when given together with or without temozolomide in treating patients with low-grade glioma.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors Neurotoxicity	Drug: temozolomide Radiation: 3-dimensional conformal radiation therapy Radiation: intensity-modulated radiation therapy	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Primary Purpose: Treatment
Official Title:	Phase III Study of Radiation Therapy With or Without Temozolomide for Symptomatic or Progressive Low-Grade Gliomas

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Temozolomide

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Progression-free survival (PFS) [ Designated as safety issue: No ]
Overall survival (OS) [ Designated as safety issue: No ]

Secondary Outcome Measures:

Quality of life as assessed by the FACT-BR questionnaire at baseline, annually until disease progression, and at the time of disease progression [ Designated as safety issue: No ]
Neurocognitive functioning as assessed at baseline, annually until disease progression, and at the time of disease progression [ Designated as safety issue: No ]
Correlation of pre-treatment 1p and 19q levels in tumor tissue samples with PFS and OS [ Designated as safety issue: No ]

Estimated Enrollment:	540
Study Start Date:	September 2009
Estimated Primary Completion Date:	March 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Active Comparator Patients undergo 3-dimensional conformal or intensity-modulated radiotherapy once daily 5 days a week for 5½ weeks (28 fractions).	Radiation: 3-dimensional conformal radiation therapy Given once daily 5 days a week for 5½ weeks Radiation: intensity-modulated radiation therapy Given once daily 5 days a week for 5½ weeks
Arm II: Experimental Patients undergo radiotherapy as in arm I and receive concurrent oral temozolomide once daily for 5½ weeks. Beginning 28 days after completion of chemoradiotherapy, patients receive oral temozolomide alone once daily on days 1-5. Treatment with temozolomide repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.	Drug: temozolomide Given orally Radiation: 3-dimensional conformal radiation therapy Given once daily 5 days a week for 5½ weeks Radiation: intensity-modulated radiation therapy Given once daily 5 days a week for 5½ weeks

Detailed Description:

OBJECTIVES:

Primary

To determine whether the addition of temozolomide to fractionated radiotherapy improves the progression-free survival (PFS) of patients with symptomatic or progressive low-grade gliomas.
To determine whether the addition of temozolomide to fractionated radiotherapy improves the median overall survival (OS) of these patients.

Secondary

To determine whether combination therapy with temozolomide and radiotherapy improves or maintains cognition and quality of life compared to radiotherapy alone.
To compare the toxicities (severe or worse [≥ grade 3]) of radiotherapy with vs without temozolomide in these patients.
To assess the impact of the presence or absence of 1p and 19q deletion on PFS and OS.
To determine the impact of 1p and 19q status on PFS and OS of patients treated with temozolomide.
To create a tumor and tissue bank, including plasma and germ line DNA, within the ECOG Pathology Coordinating Office.

OUTLINE: This is a multicenter study. Patients are stratified according to age (< 40 years vs ≥ 40 years), 1p and 19q status (both deleted vs either/both intact vs undeterminable), pre-operative maximum tumor diameter (< 6 cm vs ≥ 6 cm [based on T2 or FLAIR MRI]), Karnofsky performance status (60-70% vs 80-100%), and contrast enhancement on pre-treatment MRI scan (present vs absent). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients undergo 3-dimensional conformal or intensity-modulated radiotherapy once daily 5 days a week for 5½ weeks (28 fractions).
Arm II: Patients undergo radiotherapy as in arm I and receive concurrent oral temozolomide once daily for 5½ weeks. Beginning 28 days after completion of chemoradiotherapy, patients receive oral temozolomide alone once daily on days 1-5. Treatment with temozolomide repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

Some patients undergo quality-of-life and neurocognitive (e.g., visual scanning speed, divided attention, language, memory, and fine motor skills) assessments at baseline, annually until disease progression, and at the time of disease progression.

Tumor tissue samples are collected at baseline for confirmation of diagnosis and determination of 1p and 19q deletion status. Peripheral blood, serum, and additional tumor tissue samples may be collected for further research studies.

After completion of study treatment, patients are followed up periodically for up to 15 years.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed* supratentorial low-grade glioma, including 1 of the following:
- Grade 2 astrocytoma
- Grade 2 oligodendroglioma
- Grade 2 oligoastrocytoma (mixed glioma containing astrocytoma and oligodendroglioma)
NOTE: *If the pathology from multiple procedures supports the diagnosis of a brain tumor, the qualifying pathology of grade 2 astrocytoma, oligodendroglioma, or oligoastrocytoma must be the most recent pathological diagnosis; no pathological diagnosis of grade 3 or 4 glioma at any time
Paraffin-embedded tumor specimen available for submission for confirmation of pathological diagnosis and determination of 1p and 19q deletion status
Patients must currently meet ≥ 1 of the following criteria*:
- Uncontrolled symptoms, defined as any of the following:
  - Headaches associated with mass effect
  - Uncontrolled seizures despite two different antiepileptic drug regimens (i.e., two antiepileptic drugs tested either sequentially or in combination)
  - Focal neurological symptoms
  - Cognitive symptoms or deficits
- Tumor progression by serial MRIs, defined as any of the following:
  - New or progressive enhancement
  - New or progressive T2 or FLAIR signal abnormality
- Age ≥ 40 years
NOTE: *Patients < 40 years of age whose only symptom of low-grade glioma is seizures that are well-controlled on antiepileptic drugs AND who have no evidence of radiographic progression are not eligible.
Patients who have undergone gross total resection and have no detectable residual disease are eligible
No pilocytic astrocytoma, ganglioglioma, pleomorphic xanthoastrocytoma, or dysembryoplastic neuroepithelial tumors

PATIENT CHARACTERISTICS:

Karnofsky performance status 60-100%
WBC ≥ 3,000/mm^3
ANC ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Hematocrit ≥ 30%
Bilirubin ≤ 2 times upper limit of normal (ULN)
AST and ALT ≤ 3 times ULN
Creatinine ≤ 2.0 times ULN
Not pregnant or nursing
Negative pregnancy test
Able to undergo MRI with and without contrast
No other malignancy within the past 5 years, except for nonmelanoma skin cancer or cervical carcinoma in situ
No uncontrolled infection
No known HIV positivity
No medical disorder that would increase risks associated with radiotherapy and temozolomide
No other disorder that would limit life expectancy to < 5 years

PRIOR CONCURRENT THERAPY:

No prior radiotherapy, cytotoxic chemotherapy, radiosurgery, or investigational therapy directed at the brain tumor
- Any number of prior surgical procedures for the brain tumor allowed
No prior radiotherapy to the head unless the radiotherapy ports entirely excluded the brain
At least 2 weeks since prior brain surgery

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00978458

Show 184 Study Locations

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

David Schiff, MD

University of Virginia

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	ECOG Group Chair's Office ( Robert L. Comis )
ClinicalTrials.gov Identifier:	NCT00978458 History of Changes
Other Study ID Numbers:	CDR0000654697, ECOG-E3F05
Study First Received:	September 16, 2009
Last Updated:	August 31, 2010
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

neurotoxicity
adult diffuse astrocytoma
adult oligodendroglioma
recurrent adult brain tumor
adult mixed glioma

Additional relevant MeSH terms:

Temozolomide
Glioma
Nervous System Neoplasms
Central Nervous System Neoplasms
Neurotoxicity Syndromes
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
Poisoning
Disorders of Environmental Origin
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 07, 2010