NCT00626990 · CITED IN SOURCE DOCUMENTS

Phase III Trial of Anaplastic Glioma Without 1p/19q Loss of Heterozygosity (LOH)

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: ACTIVE NOT RECRUITING
Registry last update: 2023-09-11

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. 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. Giving radiation therapy together with temozolomide may kill more tumor cells. It is not yet known whether giving temozolomide during and/or after radiation therapy is more effective than radiation therapy alone in treating anaplastic glioma. PURPOSE: This randomized phase III trial is studying giving temozolomide during and/or after radiation therapy to see how well it works compared to radiation therapy alone in treating patients with anaplastic glioma.

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What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Overall Survival as Measured From the Day of Randomization

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outcome · POSTED

Progression-free Survival

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outcome · NOT POSTED

Quality of Life of the Patient

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outcome · NOT POSTED

Neurological Deterioration Free Survival

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: DISEASE CHARACTERISTICS: * Histologically confirmed diagnosis of 1 of the following: * Anaplastic oligodendroglioma * Anaplastic oligoastrocytoma * Anaplastic astrocytoma * Newly diagnosed disease * Prior surgery for a low grade tumor is allowed, provided histological confirmation of an anaplastic tumor is present at the time of progression * Absence of combined 1p/19q loss * Tumor material available for central 1p/19q assessment, central O6-methylguanine-DNA methyltransferase promoter methylation status assessment, isocitrate dehydrogenase mutation analysis, and central pathology review * Patients must be on a stable or decreasing dose of steroids for at least two weeks prior to randomization PATIENT CHARACTERISTICS: * WHO performance status 0-2 * Absolute Neutrophil Count (ANC) ≥ 1.5 x 10\^9 cells/L * Platelet count ≥ 100 x 10\^9 cells/L * Bilirubin \< 1.5 x upper limit of normal (ULN) * Alkaline phosphatase \< 2.5 x ULN * Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) \< 2.5 x ULN * Serum creatinine \< 1.5 x ULN * Not pregnant or nursing * Fertile patients must use effective contraception * No known HIV infection or chronic hepatitis B or hepatitis C infection * No other serious medical condition that would interfere with follow-up * No medical condition that could interfere with oral medication intake (e.g., frequent vomiting or partial bowel obstruction) * No other prior malignancies except for any malignancy which was treated with curative intent more than 5 years prior to registration and adequately controlled limited basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix * No prior or concurrent malignancies at other sites except for surgically cured carcinoma in situ of the cervix or nonmelanoma skin cancer * No psychological, familial, sociological, or geographical condition that would potentially hamper compliance with the study protocol and follow-up schedule PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No prior chemotherapy, including carmustine-containing wafers (Gliadel®) * No prior radiotherapy to the brain * No concurrent growth factors unless vital for the patient * No other concurrent investigational treatment * No other concurrent anticancer agents
healthy Volunteers: false
maximum Age: 120 Years
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
radiation therapy alone
intervention Names
Genetic: DNA methylation analysis
Other: laboratory biomarker analysis
Procedure: quality-of-life assessment
Radiation: radiation therapy
label
Radiotherapy (RT) alone
type
ACTIVE_COMPARATOR
description
Radiotherapy and concurrent temozolomide chemotherapy
intervention Names
Drug: temozolomide
Genetic: DNA methylation analysis
Other: laboratory biomarker analysis
Procedure: quality-of-life assessment
Radiation: radiation therapy
label
RT & Concurrent CT
type
ACTIVE_COMPARATOR
description
Radiotherapy plus adjuvant temozolomide chemotherapy
intervention Names
Drug: temozolomide
Genetic: DNA methylation analysis
Other: laboratory biomarker analysis
Procedure: adjuvant therapy
Procedure: quality-of-life assessment
Radiation: radiation therapy
label
RT + Adjuvant CT
type
ACTIVE_COMPARATOR
description
Radiotherapy and concurrent chemotherapy plus adjuvant temozolomide chemotherapy
intervention Names
Drug: temozolomide
Genetic: DNA methylation analysis
Other: laboratory biomarker analysis
Procedure: adjuvant therapy
Procedure: quality-of-life assessment
Radiation: radiation therapy
label
RT & Concurrent CT + adjuvant CT
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
RT & Concurrent CT
RT & Concurrent CT + adjuvant CT
RT + Adjuvant CT
description
Patients randomized to concomitant temozolomide will receive temozolomide continuously at a daily dose of 75 mg/m² during radiotherapy.
name
temozolomide
other Names
Temodar
Temodal
type
DRUG
arm Group Labels
RT & Concurrent CT
RT & Concurrent CT + adjuvant CT
RT + Adjuvant CT
Radiotherapy (RT) alone
description
O6-Methylguanine-DNA Methyltransferase (MGMT) methylation status is used for stratification at randomization.
name
DNA methylation analysis
type
GENETIC
arm Group Labels
RT & Concurrent CT
RT & Concurrent CT + adjuvant CT
RT + Adjuvant CT
Radiotherapy (RT) alone
description
Prognostic factor analyses
name
laboratory biomarker analysis
type
OTHER
arm Group Labels
RT & Concurrent CT + adjuvant CT
RT + Adjuvant CT
description
Patients randomized to adjuvant temozolomide will start adjuvant temozolomide after a 4 week resting period after the end of radiotherapy.
name
adjuvant therapy
type
PROCEDURE
arm Group Labels
RT & Concurrent CT
RT & Concurrent CT + adjuvant CT
RT + Adjuvant CT
Radiotherapy (RT) alone
description
Quality of Life analysis will also be used to assess neurological deterioration free progression
name
quality-of-life assessment
type
PROCEDURE
arm Group Labels
RT & Concurrent CT
RT & Concurrent CT + adjuvant CT
RT + Adjuvant CT
Radiotherapy (RT) alone
description
Radiotherapy will consist of a conventionally fractionated regimen for 6.5 weeks in a once daily schedule
name
radiation therapy
type
RADIATION

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 751
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
The duration of survival is the time interval between randomization and the date of death due to any cause. Patients not reported dead or lost to follow up will be censored at the date of the last follow up examination.
measure
Overall Survival as Measured From the Day of Randomization
time Frame
from date from enrollment till the date of death (time till death is up to 10.9 years after patient enrollment in the study)

secondary Outcomes

description
Disease progression is defined as radiological or neurological/clinical progression (whichever occurs first); progression free survival (PFS) is the time interval between the date of randomization and the date of disease progression or death whichever occurs first. If neither event has been observed, the patient is censored at the date of the last follow up examination. Radiological progression was defined as increase of contrast enhancing area on MRI or CT scans of more than 25% as measured by two perpendicular diameters compared to the smallest measurements ever recorded for the same lesion by the same technique. The appearance of new lesions with or without contrast enhancement Neurological/clinical progression was defined as:decrease in WHO performance status,deterioration of neurological functions,appearance of signs/symptoms of increased intracranial pressure,and/or start of corticosteroid or increase of corticosteroid dosage by 50% for control of neurological symptoms.
measure
Progression-free Survival
time Frame
from randomization till the date of disease progression or death (time till death is up to 10.9 years after patient enrollment in the study)
description
Quality of life was assessed by the EORTC Quality of Life Questionnaire (QLQ-C30) version 3 and the Brain Cancer Module-20
measure
Quality of Life of the Patient
time Frame
from 14 days prior to randomization till five years or death (time till death is up to 10.9 years after patient enrollment in the study)
description
Neurological deterioration is defined as a decrease in WHO performance status as follows: decrease in WHO performance status * for patients with baseline WHO performance status 0: deterioration to WHO performance status 2 or worse for which no other explanation is present, and which is maintained for at least three months * for patients with baseline WHO performance status 1 or 2: deterioration to WHO performance status 3 or worse for which no other explanation is present and which is maintained for at least three months The date of neurological deterioration will be the first date the persistent decrease in performance status was diagnosed. Neurological deterioration free progression is the time interval between the date of randomization and the date of neurological deterioration or death whichever occurs first. If neither event has been observed, the patient is censored at the date of the last follow up examination
measure
Neurological Deterioration Free Survival
time Frame
within 2 weeks of randomization; during radiotherapy at week 4 and 6; 4 weeks after the end of radiotherapy; Six monthly after the end of radiotherapy; Prior to each cycle of adjuvant therapy; Every six months after the documentation of first progression.

Full study description

brief Summary: RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. 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. Giving radiation therapy together with temozolomide may kill more tumor cells. It is not yet known whether giving temozolomide during and/or after radiation therapy is more effective than radiation therapy alone in treating anaplastic glioma. PURPOSE: This randomized phase III trial is studying giving temozolomide during and/or after radiation therapy to see how well it works compared to radiation therapy alone in treating patients with anaplastic glioma.
detailed Description: OBJECTIVES: Primary * To assess whether concurrent radiotherapy with daily temozolomide improves overall survival as compared to no daily temozolomide in patients with non-1p/19q deleted anaplastic glioma. * To assess whether adjuvant temozolomide improves survival as compared to no adjuvant temozolomide in patients with non-1p/19q deleted anaplastic glioma. Secondary * To assess whether concurrent and adjuvant temozolomide prolongs progression-free survival and neurological deterioration-free survival in patients with non-1p/19q deleted anaplastic glioma. * To assess the safety of concurrent and adjuvant temozolomide in patients with non-1p/19q deleted anaplastic glioma, including late effects on cognition. * To assess the impact of concurrent and adjuvant temozolomide on the quality of life of patients with non-1p/19q deleted anaplastic glioma. OUTLINE: This is a multicenter study. Patients are stratified according to institution, World Health Organization (WHO) performance status (0 vs \> 0), age (≤ 50 vs \> 50), presence of 1p LOH only (yes vs no), presence of oligodendroglial elements (yes vs no), and O6-methylguanine-DNA methyltransferase promoter methylation status (methylated vs unmethylated vs indeterminate). Patients are randomized to 1 of 4 treatment arms. * Arm I: Patients undergo radiotherapy\* once daily, 5 days a week, for 6.5 weeks (total of 33 fractions). * Arm II: Patients undergo radiotherapy\* once daily, 5 days a week and receive oral temozolomide once daily for 6.5 weeks (total of 33 fractions of radiotherapy). * Arm III: Patients undergo radiotherapy\* once daily, 5 days a week for 6.5 weeks (total of 33 fractions). Beginning 4 weeks after completion of radiotherapy, patients receive adjuvant oral temozolomide once daily on days 1-5. Treatment with adjuvant temozolomide repeats every 28 days for up to 12 courses. * Arm IV: Patients undergo radiotherapy\* once daily, 5 days a week and receive oral temozolomide once daily for 6.5 weeks (total of 33 fractions of radiotherapy). Beginning 4 weeks after completion of radiotherapy, patients receive adjuvant oral temozolomide once daily on days 1-5. Treatment with adjuvant temozolomide repeats every 28 days for up to 12 courses. * Patients must begin radiotherapy within 8 days after randomization and within 7 weeks after surgery. In all arms, treatment continues in the absence of disease progression or unacceptable toxicity. Patients complete quality-of-life questionnaires, including EORTC core quality of life questionnaire (QLQ-C30) version 3, EORTC brain cancer module (BCM20), and the Mini Mental Status Exam at baseline, 4 weeks after the completion of radiotherapy, and then every 3 months for 5 years. Tissue samples are collected at baseline for histology review, 1p/19q analysis, methylation status of the O6-methylguanine-DNA methyltransferase promoter, and isocitrate dehydrogenase mutation analysis. After completion of study treatment, patients are followed every 3 months.

Source references

references

citation
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pmid
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type
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citation
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pmid
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type
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28801186
type
DERIVED