Clinical trial NCT00075491: Neoadjuvant and Adjuvant Fenretinide Compared With Adjuvant Fenretinide Alone in Treating Patients Who Are Undergoing Surgical Resection For Recurrent Glioblastoma Multiforme
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Recurrent Adult Brain Tumor
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2004-01-12
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: 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.

Eligibility criteria: 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

  * Enhancing or nonenhancing recurrent disease by MRI
* 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)

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Up to 6 months
measure: Plasma and tissue concentrations of fenretinide and its metabolite, 4-MPR using high-performance liquid chromatography (HPLC) assay
timeFrame: At baseline, and at 1, 7, 14, and 21 days
measure: Tumor apoptotic index after fenretinide treatment by immunohistochemistry
timeFrame: At the time of surgery
measure: Correlation between tumor apoptotic index with serum and tissue fenretinide levels
timeFrame: At the time of surgery
measure: Correlation of time to progression with drug levels and apoptotic index
timeFrame: Up to 2 years
Secondary outcomes:
measure: Fenretinide effects on retinol, RBP, retinoid receptor levels and IGF-1
timeFrame: Up to 21 days (course 1 and 4)
measure: Fenretinide activity using magnetic resonance spectroscopy (MRS)
timeFrame: At the time of surgery
measure: Radiological response
timeFrame: Up to 2 years
measure: Overall survival
timeFrame: Up to 2 years
measure: Unexpected toxicity associated with fenretinide as assessed by CTC version 3.0
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Vinay K. Puduvalli
role: PRINCIPAL_INVESTIGATOR
References: