Fenretinide in Treating Patients With Recurrent Malignant Glioma

OBJECTIVES: I. Determine the efficacy of fenretinide as assessed by 6-month progression- free
survival in patients with recurrent malignant glioma. II. Determine the rate of measurable
clinical response, time to progression, and overall survival of patients treated with this
drug. III. Determine the unexpected toxicity of this drug in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to disease type
(glioblastoma multiforme (closed to accrual as of 05/31/2001) and gliosarcoma (closed to
accrual as of 05/31/2001) vs anaplastic astrocytoma, anaplastic oligodendroglioma, and mixed
malignant glioma). Patients receive oral fenretinide twice daily during weeks 1 and 4.
Treatment repeats every 6 weeks in the absence of disease progression or unacceptable
toxicity. Quality of life is assessed at baseline and then before each course of
chemotherapy. Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 41-85 patients (21-45 with anaplastic astrocytoma, anaplastic
oligodendroglioma, and mixed malignant glioma and 20-40 with glioblastoma multiforme (closed
to accrual as of 05/31/2001) and gliosarcoma (closed to accrual as of 05/31/2001)) will be
accrued for this study.

DISEASE CHARACTERISTICS: Histologically confirmed supratentorial malignant primary glioma
Glioblastoma multiforme (closed to accrual as of 05/31/2001) Gliosarcoma (closed to accrual
as of 05/31/2001) Anaplastic astrocytoma Anaplastic oligodendroglioma Mixed malignant
gliomas Original histological diagnosis of low-grade glioma allowed if a subsequent
histological diagnosis of malignant glioma is confirmed Prior treatment for no more than 2
prior relapses allowed Disease progression documented by at least 2 pre-study brain scans
Recent prior tumor resection of recurrent or progressive tumor allowed if recovered from
the effects of prior surgery

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 70-100% Life
expectancy: More than 8 weeks Hematopoietic: Absolute neutrophil count at least 1,500/mm3
Platelet count at least 100,000/mm3 Hemoglobin at least 10 g/dL (may be transfusion
dependent) Hepatic: Bilirubin less than 2 times upper limit of normal (ULN) SGOT less than
2 times ULN Renal: Creatinine less than 1.5 mg/dL Creatinine clearance at least 60 mL/min
Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective
barrier contraception during and for at least 2 months after study Able to swallow capsules
No active infection No disease or other serious concurrent medical illness that would
preclude study

PRIOR CONCURRENT THERAPY: Biologic therapy: At least 1 week since prior interferon At least
1 week since prior thalidomide Chemotherapy: Recovered from prior chemotherapy At least 4
weeks since prior cytotoxic therapy (2 weeks for vincristine, 3 weeks for procarbazine, or
6 weeks for nitrosoureas) Endocrine therapy: At least 1 week since prior tamoxifen Prior
steroids allowed if on stable or decreasing dose for at least 5-7 days before baseline MRI
If steroid dose is increased between date of baseline MRI and initiation of study drug, a
new baseline MRI is required Radiotherapy: Not specified Surgery: See Disease
Characteristics No concurrent surgery Other: At least 1 week since any prior noncytotoxic
agents (e.g., isotretinoin) No other concurrent anticancer therapy, including other
investigational drugs