Radiation Therapy, Temozolomide, and Irinotecan in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

Radiation Therapy Oncology Group

Status and phase

Completed

Phase 2

Conditions

Brain and Central Nervous System Tumors

Treatments

Procedure: adjuvant therapy

Drug: irinotecan hydrochloride

Drug: temozolomide

Radiation: radiation therapy

Study type

Interventional

Funder types

NETWORK

NIH

Identifiers

NCT00099125

RTOG-0420

CDR0000389229

Details and patient eligibility

About

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy, such as temozolomide and irinotecan, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy with chemotherapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well radiation therapy, temozolomide, and irinotecan work in treating patients with newly diagnosed glioblastoma multiforme.

Full description

OBJECTIVES:

Compare overall survival of patients with newly diagnosed supratentorial glioblastoma multiforme treated with radiotherapy and temozolomide followed by temozolomide and irinotecan with historical controls from the RTOG database.
Determine the short- and long-term toxicity of this regimen in these patients.
Determine progression-free survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

Chemoradiotherapy: Patients undergo radiotherapy once daily, 5 days a week, for 6 weeks. Concurrently with radiotherapy, patients receive oral temozolomide once daily, 7 days a week, for 6 weeks.
Post-radiotherapy chemotherapy: Beginning 4-6 weeks after the completion of chemoradiotherapy, patients receive irinotecan IV on days 1 and 15 and oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months for 2 years and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 157 patients will be accrued for this study within 11 months.

Enrollment

170 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically confirmed newly diagnosed supratentorial glioblastoma multiforme by surgical biopsy or excision
- No gliomas graded less than glioblastoma multiforme
- No recurrent malignant gliomas
No tumor foci below the tentorium or beyond the cranial vault
Study therapy must begin ≤ 5 weeks after surgery

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

Zubrod 0-1

Life expectancy

At least 8 weeks

Hematopoietic

Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Hemoglobin ≥ 10 g/dL*
Hematocrit ≥ 30%* NOTE: *Transfusion allowed

Hepatic

Bilirubin ≤ 0.5 mg/dL
ALT or AST ≤ 2 times upper limit of normal

Renal

Creatinine ≤ 1.5 mg/dL
BUN ≤ 25 mg/dL

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective double-barrier contraception during and for 2 months after study participation
No AIDS
No other malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix or bladder
No other major medical illness or psychiatric impairment that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

No concurrent sargramostim (GM-CSF)

Chemotherapy

No other concurrent chemotherapy

Endocrine therapy

Concurrent steroid therapy allowed provided patient is on a stable or decreasing dose for at least 2 weeks before study entry

Radiotherapy

No prior radiotherapy to the head or neck resulting in overlap of radiotherapy fields
- Prior radiotherapy for stage T1 glottic cancer allowed

Surgery

See Disease Characteristics
Recovered from prior surgery

Other

No enzyme-inducing antiepileptic drugs within 14 days before the initiation of irinotecan
- Concurrent non-enzyme-inducing antiepileptic drugs allowed