Primary Chemotherapy With Temozolomide Versus Radiotherapy in Patients With Low Grade Gliomas After Stratification for Genetic 1p Loss: A Phase III Study
18 Years
N/A
Both
Brain and Central Nervous System Tumors
Trial Information
Primary Chemotherapy With Temozolomide Versus Radiotherapy in Patients With Low Grade Gliomas After Stratification for Genetic 1p Loss: A Phase III Study
OBJECTIVES:
Primary
- Compare the progression-free survival of patients with low-grade gliomas treated with
radiotherapy vs temozolomide.
Secondary
- Compare the overall survival of patients treated with these regimens.
- Determine whether the incidence of late toxicity can be decreased in patients who are
randomized to receive temozolomide.
- Compare the toxic effects of these regimens in these patients.
- Compare the quality of life of patients treated with these regimens.
OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified
according to participating center, chromosome 1p status (deleted vs normal vs
undeterminable), contrast enhancement on MRI (yes vs no), age (< 40 years vs ≥ 40 years),
and WHO performance status (0 or 1 vs 2). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients undergo radiotherapy once daily, 5 days a week, for a total of 28
fractions (i.e., 5½ weeks).
- Arm II: Patients receive oral temozolomide once daily on days 1-21. Treatment repeats
every 28 days for up to 12 courses in the absence of disease progression or
unacceptable toxicity.
Quality of life is assessed at baseline and then every 3 months until disease progression.
After completion of study treatment, patients are followed every 6 months for survival.
Peer Reviewed and Funded or Endorsed by Cancer Research UK
PROJECTED ACCRUAL: A minimum of 699 patients (a total of 466 randomized [233 per treatment
arm]) will be accrued for this study within 5 years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed low-grade glioma, including any of the following types:
- Astrocytoma (gemistocytic, fibrillary, or protoplasmatic)
- Oligoastrocytoma
- Oligodendroglioma
- WHO grade II disease
- Supratentorial tumor location only
- RTOG neurological function 0-3
- Not a candidate for surgical treatment alone
- Requires treatment, as determined by ≥ 1 of the following criteria:
- Age ≥ 40 years
- Radiologically-proven progressive lesion
- New or worsening neurological symptoms other than seizures only (e.g., focal
deficits, signs of increased intracranial pressure, or mental deficits)
- Intractable seizures, defined by both of the following criteria:
- Experiences persistent seizures that interfere with everyday life
activities except driving a car
- Failed 3 anti-epileptic drug regimens, including ≥ 1 combination regimen
- Tumor material (paraffin-embedded) or histopathologic slides available
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- WHO 0-2
Life expectancy
- Not specified
Hematopoietic
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
Hepatic
- No chronic hepatitis B or C infection
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST or ALT ≤ 2.5 times ULN
- Alkaline phosphatase ≤ 2.5 times ULN
Renal
- Creatinine ≤ 1.5 times ULN
Other
- Not pregnant or nursing
- Fertile patients must use effective contraception during and for 6 months after
completion of study treatment
- No known HIV positivity
- No other serious medical condition
- No other prior or concurrent malignancy except surgically cured carcinoma in situ of
the cervix or nonmelanoma skin cancer
- No psychological, familial, sociological, or geographical condition that would
preclude study participation
- No medical condition that would preclude receiving oral medication (e.g., frequent
vomiting or partial bowel obstruction)
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No concurrent growth factors for elevating absolute neutrophil counts for the purpose
of temozolomide administration
- No concurrent epoetin alfa
- No concurrent immunotherapy or biologic therapy
Chemotherapy
- No prior chemotherapy
- No other concurrent chemotherapy, including adjuvant chemotherapy for patients
randomized to undergo radiotherapy
Endocrine therapy
- Not specified
Radiotherapy
- No prior radiotherapy to the brain
- No concurrent integrated boost with intensity-modulated radiotherapy
Surgery
- Recovered from prior surgery
- No concurrent surgical tumor debulking
Other
- No prior randomization to this study
- No other concurrent investigational drugs
- No concurrent regular use of agents known to be radiosensitizers or radioprotectors
(e.g., cyclooxygenase-2 inhibitors, thalidomide, or amifostine) during study
radiotherapy
- Occasional use of nonsteroidal anti-inflammatory drugs for pain allowed
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Progression-free survival
Outcome Time Frame:
5 years
Safety Issue:
No
Principal Investigator
Brigitta Baumert, MD, PhD
Investigator Role:
Study Chair
Investigator Affiliation:
Maastricht University Medical Center
Authority:
Canada: Health Canada
Study ID:
EORTC-22033-26033
NCT ID:
NCT00182819
Start Date:
July 2005
Completion Date:
Related Keywords:
- Brain and Central Nervous System Tumors
- adult oligodendroglioma
- adult diffuse astrocytoma
- adult mixed glioma
- Glioma
- Nervous System Neoplasms
- Central Nervous System Neoplasms
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