Leflunomide in Treating Patients With Anaplastic Astrocytoma in First Relapse
Leflunomide in Treating Patients With Anaplastic Astrocytoma in First Relapse
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
 they stop growing or die.

 PURPOSE: Phase II trial to study the effectiveness of leflunomide in treating patients who
 have anaplastic astrocytoma in first relapse.
OBJECTIVES: I. Determine the median time to progression, median survival, and objective
 response of patients with anaplastic astrocytoma or anaplastic oligoastrocytoma in first
 relapse treated with intravenous leflunomide (SU101). II. Assess the safety of SU101 in these
 patients. III. Describe the health-related quality of life of patients treated with
 intravenous SU101.

 OUTLINE: This is an open label, multicenter study. Patients receive leflunomide (SU101) IV
 over 6 hours on days 1-4. Patients then receive SU101 IV over 6 hours weekly for 6 weeks
 (beginning between days 8-12). Patients exhibiting complete response, partial response, or
 stable disease may continue on treatment for up to a year or until disease progression or
 unacceptable toxicity occurs. Patients continuing therapy receive SU101 IV over 6 hours every
 week for 7 weeks, followed by 1 week of rest. Quality of life is assessed every 8 weeks and
 at the end of the study. Patients are followed every 8 weeks or until tumor progression.

 PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.
DISEASE CHARACTERISTICS: Histologically confirmed anaplastic astrocytoma or anaplastic
 oligoastrocytoma in first relapse Recurrence or progression at least 6 months from initial
 diagnosis Must have received maximally feasible surgical resection and fractionated
 external beam radiotherapy Must have received no more than 1 prior systemic cytotoxic
 chemotherapy regimen for initial disease Bidimensionally measurable disease by MRI scan
 (stable dose of corticosteroids for at least 7 days prior to scan)

 PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life
 expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm3
 Platelet count at least 75,000/mm3 Hemoglobin at least 9 g/dL Hepatic: AST no greater than
 3 times upper limit of normal (ULN) Bilirubin less than 1.5 times ULN Renal: Creatinine no
 greater than 2 mg/dL OR Creatinine clearance at least 40 mL/min Other: Not pregnant or
 nursing Negative pregnancy test Fertile patients must use effective contraception during
 and for 3 months after the study No known allergy to etoposide No other acute or chronic
 medical illness or psychiatric disorder

 PRIOR CONCURRENT THERAPY: Biologic therapy: At least 4 weeks since prior epoetin alfa,
 filgrastim (G-CSF), or sargramostim (GM-CSF) and recovered No concurrent immunotherapy
 Chemotherapy: See Disease Characteristics At least 4 weeks since prior chemotherapy (2
 weeks since vincristine; 6 weeks since nitrosoureas or mitomycin) and recovered No prior
 leflunomide (SU101) therapy No other concurrent chemotherapy Endocrine therapy: No
 concurrent hormonal therapy (except medroxyprogesterone acetate for appetite stimulation)
 Radiotherapy: See Disease Characteristics No more than 1 prior course of radiotherapy At
 least 8 weeks since prior radiotherapy and recovered No prior interstitial radiotherapy or
 implanted carmustine wafers Prior radiosensitizer(s) concurrent with radiotherapy or used
 as neoadjuvant therapy allowed No concurrent radiotherapy Surgery: See Disease
 Characteristics No more than 2 prior surgical resections At least 1 week since prior
 surgery or biopsy for anaplastic astrocytoma No concurrent surgery (including resection,
 stereotactic surgery, or interstitial implants) Other: At least 4 weeks since prior
 investigational agents No other concurrent investigational agents