Temozolomide Plus Lomustine Followed by Radiation Therapy in Treating Patients With High-Grade Malignant Glioma

Children's Oncology Group

Status and phase: Completed; Phase 1

Conditions: Brain Tumor; Central Nervous System Tumor

Treatments: Drug: temozolomide; Drug: lomustine

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00006024

COG-ADVL0011 (Other Identifier)

CCG-A0993 (Other Identifier)

ADVL0011

CDR0000068036 (Other Identifier)

CCG-ADVL0011 (Other Identifier)

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining more than one chemotherapy drug with radiation therapy may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of temozolomide plus lomustine followed by radiation therapy in treating patients who have high-grade malignant glioma.

Full description

OBJECTIVES:

• Determine the maximum tolerated dose of temozolomide when administered with lomustine in patients with high-grade malignant gliomas.
• Determine the dose-limiting toxic effects of this regimen in these patients.
• Evaluate the feasibility of radiotherapy after this treatment regimen in this patient population.
• Evaluate the radiographic responses in patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of temozolomide.

Patients receive oral temozolomide on days 1-5 and oral lomustine on day 1. Treatment continues every 28 days, if blood counts have recovered, for 2 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo radiotherapy on days 1-5 weekly for 6 weeks. Patients continue the same chemotherapy regimen for up to 6 more courses beginning 4 weeks after completion of radiotherapy.

Cohorts of 3-6 patients receive escalating doses of temozolomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for this study.

Enrollment: 32 patients

Sex: All

Ages: 3 to 21 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed high-grade malignant glioma of one of the following subtypes:

  • Glioblastoma
  • Anaplastic astrocytoma
  • Anaplastic oligoastrocytoma
  • Gliomatosis cerebri

• No disseminated disease or primary spinal cord malignancies

• Measurable intracranial residual disease by MRI

PATIENT CHARACTERISTICS:

Age:

• 3 and over
• Under 22 at time of diagnosis

Performance status:

• Karnofsky 50-100% if over 10 years of age
• Lansky 50-100% if 10 years of age or under

Life expectancy:

• At least 8 weeks

Hematopoietic:

• Absolute neutrophil count at least 1,000/mm^3
• Platelet count at least 100,000/mm^3 (transfusion independent)
• Hemoglobin at least 8.0 g/dL (RBC transfusions allowed)

Hepatic:

• Bilirubin no greater than 1.5 times normal for age
• SGPT no greater than 2.5 times normal for age
• Albumin at least 2 g/dL

Renal:

• Creatinine no greater than 1.5 times normal for age OR
• Creatinine clearance or radioisotope glomerular filtration rate at least lower limit of normal for age

Pulmonary:

• No dyspnea at rest
• No exercise intolerance
• Pulse oximetry at least 94%

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No uncontrolled infection

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior biologic therapy
• No concurrent prophylactic hematopoietic growth factors

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Prior corticosteroid therapy allowed
• No concurrent corticosteroids as antiemetic

Radiotherapy:

• No prior radiotherapy

Surgery:

• No more than 31 days since prior maximal neurosurgical procedure

Other:

• No concurrent phenobarbital or cimetidine

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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32 participants in 1 patient group

Pre and Post radiation Chemotherapy

Experimental group

Treatment:

Drug: temozolomide

Drug: lomustine