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

Study Overview

• Status: Terminated
• Conditions: Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Recurrent Adult Brain Tumor
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: pharmacological study; Procedure: therapeutic conventional surgery; Drug: fenretinide

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.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (fenretinide, surgery); Patients receive neoadjuvant oral fenretinide twice daily for 1 week and then undergo surgical resection.	Other: laboratory biomarker analysis; Correlative studies; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies; Procedure: therapeutic conventional surgery; Undergo surgery; Drug: fenretinide; Given orally; Other Names: fenretinimide; McN-R-1967
Active Comparator: Arm II (surgery); Patients undergo surgical resection.	Other: laboratory biomarker analysis; Correlative studies; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies; Procedure: therapeutic conventional surgery; Undergo surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival (PFS)	Up to 6 months
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
Tumor apoptotic index after fenretinide treatment by immunohistochemistry	At the time of surgery
Correlation between tumor apoptotic index with serum and tissue fenretinide levels	At the time of surgery
Correlation of time to progression with drug levels and apoptotic index	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	Up to 2 years
Fenretinide effects on retinol, RBP, retinoid receptor levels and IGF-1	Up to 21 days (course 1 and 4)
Fenretinide activity using magnetic resonance spectroscopy (MRS)	At the time of surgery
Radiological response	Up to 2 years
Unexpected toxicity associated with fenretinide as assessed by CTC version 3.0	Up to 2 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Vinay K. Puduvalli, M.D. Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start: December 1, 2003
• Primary Completion (Actual): March 1, 2005
• Study Completion: December 7, 2022

Study Registration Dates

• First Submitted: January 9, 2004
• First Submitted That Met QC Criteria: January 11, 2004
• First Posted (Estimate): January 12, 2004

Study Record Updates

• Last Update Posted (Estimate): January 24, 2013
• Last Update Submitted That Met QC Criteria: January 23, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Disease Attributes; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Recurrence; Gliosarcoma; Physiological Effects of Drugs; Antineoplastic Agents; Protective Agents; Anticarcinogenic Agents; Fenretinide
• Other Study ID Numbers: NCI-2012-02566; ID02-701; R21CA097767 (U.S. NIH Grant/Contract); CDR0000346722 (Registry Identifier: PDQ (Physician Data Query))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No