A Phase II Evaluation With Correlative Studies Of Fenretinide (NSC 374551-4HPR) As A Single Agent In The Treatment Of Adult Patients With Recurrent Glioblastoma Multiforme
A Phase II Evaluation With Correlative Studies Of Fenretinide (NSC 374551-4HPR) As A Single Agent In The Treatment Of Adult Patients With Recurrent Glioblastoma Multiforme
This randomized phase II trial is studying how well neoadjuvant and adjuvant fenretinide works compared to adjuvant fenretinide alone in treating patients who are undergoing surgical resection for recurrent glioblastoma multiforme. Chemotherapy drugs, such as fenretinide, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving chemotherapy before surgery may shrink the tumor so that it can be removed. Giving chemotherapy after surgery may kill any remaining tumor cells. It is not yet known whether neoadjuvant and adjuvant fenretinide is more effective than adjuvant fenretinide alone
PRIMARY OBJECTIVES:
I. Compare the efficacy of neoadjuvant and adjuvant fenretinide vs adjuvant fenretinide alone, in terms of 6-month progression-free survival, in patients with recurrent glioblastoma multiforme undergoing surgical resection II. Correlate the serum and glioma tissue pharmacology of this drug with clinical response in patients treated with these regimens.
III. Determine whether this drug induces apoptosis in glioma tissue in patients treated with these regimens.
IV. Correlate the apoptotic index with tissue and serum concentration and clinical response in patients treated with these regimens.
V. Compare radiological response, overall survival, and unexpected toxicity in patients treated with these regimens.
OUTLINE: This is a randomized study. Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients receive neoadjuvant oral fenretinide twice daily for 1 week and then undergo surgical resection.
Arm II: Patients undergo surgical resection.
Beginning two weeks after surgery, all patients receive adjuvant oral fenretinide twice daily on weeks 1 and 4. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
PROJECTED ACCRUAL: A total of 21-46 patients (10-23 per treatment arm) will be accrued for this study within 7-46 months.
Inclusion Criteria:
Histologically confirmed glioblastoma multiforme after initial tumor resection
Radiologically evident recurrent tumor after prior radiotherapy OR after treatment for no more than 2 prior relapses
No progressive symptoms requiring urgent surgery
Performance status - Karnofsky 70-100%
More than 8 weeks
Absolute granulocyte count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
PT/PTT no greater than upper limit of normal
SGPT no greater than 2.5 times normal
Alkaline phosphatase no greater than 2.5 times normal
Bilirubin less than 1.5 mg/dL
BUN no greater than 1.5 times normal
Creatinine no greater than 1.5 times normal
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective barrier contraception during and for 2 months after study participation
Amylase and lipase normal
No active infection
No other disease that would obscure toxicity or dangerously alter drug metabolism
No other concurrent serious medical illness
Not at risk from any study treatment delays
Able to swallow fenretinide capsules
Recovered from all prior chemotherapy
Approximately 2 weeks since prior vincristine
Approximately 6 weeks since prior nitrosoureas
Approximately 3 weeks since prior procarbazine
See Disease Characteristics
At least 2 weeks since prior radiotherapy
See Disease Characteristics
At least 1 week since prior vitamin A
At least 1 week since prior isotretinoin (Accutane®)
No concurrent vitamin A during and for 2 weeks after study participation
No concurrent antioxidants (e.g., ascorbic acid or vitamin E)