Neoadjuvant and Adjuvant Fenretinide Compared With Adjuvant Fenretinide Alone in Treating Patients Who Are Undergoing Surgical Resection For Recurrent Glioblastoma Multiforme

Adult Glioblastoma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00075491
• Other study ID #: NCI-2012-02566
• Secondary ID: ID02-701R21CA097
• Status: Terminated
• Phase: Phase 2
• First received: January 9, 2004
• Last updated: January 23, 2013
• Start date: December 2003

Study information

• Verified date: January 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 42
• Est. primary completion date: March 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adult Giant Cell Glioblastoma
• Adult Glioblastoma
• Adult Gliosarcoma
• Glioblastoma
• Gliosarcoma
• Recurrent Adult Brain Tumor

Intervention

Drug:
• fenretinide
Given orally

Procedure:
• therapeutic conventional surgery
Undergo surgery

Other:
• pharmacological study
Correlative studies
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	M D Anderson Cancer Center	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS)		Up to 6 months	No
Primary	Plasma and tissue concentrations of fenretinide and its metabolite, 4-MPR using high-performance liquid chromatography (HPLC) assay		At baseline, and at 1, 7, 14, and 21 days	No
Primary	Tumor apoptotic index after fenretinide treatment by immunohistochemistry		At the time of surgery	No
Primary	Correlation between tumor apoptotic index with serum and tissue fenretinide levels		At the time of surgery	No
Primary	Correlation of time to progression with drug levels and apoptotic index		Up to 2 years	No
Secondary	Fenretinide effects on retinol, RBP, retinoid receptor levels and IGF-1		Up to 21 days (course 1 and 4)	No
Secondary	Fenretinide activity using magnetic resonance spectroscopy (MRS)		At the time of surgery	No
Secondary	Radiological response		Up to 2 years	No
Secondary	Overall survival		Up to 2 years	No
Secondary	Unexpected toxicity associated with fenretinide as assessed by CTC version 3.0		Up to 2 years	Yes