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

This study has been terminated.
(Administratively complete.)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00075491
First received: January 9, 2004
Last updated: January 23, 2013
Last verified: January 2013
  Purpose

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


Condition Intervention Phase
Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Recurrent Adult Brain Tumor
Drug: fenretinide
Procedure: therapeutic conventional surgery
Other: pharmacological study
Other: laboratory biomarker analysis
Phase 2

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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
  • Plasma and tissue concentrations of fenretinide and its metabolite, 4-MPR using high-performance liquid chromatography (HPLC) assay [ Time Frame: At baseline, and at 1, 7, 14, and 21 days ] [ Designated as safety issue: No ]
  • Tumor apoptotic index after fenretinide treatment by immunohistochemistry [ Time Frame: At the time of surgery ] [ Designated as safety issue: No ]
  • Correlation between tumor apoptotic index with serum and tissue fenretinide levels [ Time Frame: At the time of surgery ] [ Designated as safety issue: No ]
  • Correlation of time to progression with drug levels and apoptotic index [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Fenretinide effects on retinol, RBP, retinoid receptor levels and IGF-1 [ Time Frame: Up to 21 days (course 1 and 4) ] [ Designated as safety issue: No ]
  • Fenretinide activity using magnetic resonance spectroscopy (MRS) [ Time Frame: At the time of surgery ] [ Designated as safety issue: No ]
  • Radiological response [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Unexpected toxicity associated with fenretinide as assessed by CTC version 3.0 [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]

Enrollment: 42
Study Start Date: December 2003
Primary Completion Date: March 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (fenretinide, surgery)
Patients receive neoadjuvant oral fenretinide twice daily for 1 week and then undergo surgical resection.
Drug: fenretinide
Given orally
Other Names:
  • fenretinimide
  • McN-R-1967
Procedure: therapeutic conventional surgery
Undergo surgery
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies
Active Comparator: Arm II (surgery)
Patients undergo surgical resection.
Procedure: therapeutic conventional surgery
Undergo surgery
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00075491

Locations
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Investigators
Principal Investigator: Vinay K. Puduvalli M.D. Anderson Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00075491     History of Changes
Other Study ID Numbers: NCI-2012-02566, ID02-701, R21CA097767, CDR0000346722
Study First Received: January 9, 2004
Last Updated: January 23, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Glioblastoma
Gliosarcoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue

ClinicalTrials.gov processed this record on September 18, 2014