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

NCT ID: NCT00075491

Last Updated: 2013-01-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-12-31

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Arm I (fenretinide, surgery)

Patients receive neoadjuvant oral fenretinide twice daily for 1 week and then undergo surgical resection.

Group Type: EXPERIMENTAL

fenretinide

Intervention Type: DRUG

Given orally

therapeutic conventional surgery

Intervention Type: PROCEDURE

Undergo surgery

pharmacological study

Intervention Type: OTHER

Correlative studies

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Arm II (surgery)

Patients undergo surgical resection.

Group Type: ACTIVE_COMPARATOR

therapeutic conventional surgery

Intervention Type: PROCEDURE

Undergo surgery

pharmacological study

Intervention Type: OTHER

Correlative studies

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

fenretinide

Given orally

Intervention Type: DRUG

therapeutic conventional surgery

Undergo surgery

Intervention Type: PROCEDURE

pharmacological study

Correlative studies

Intervention Type: OTHER

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

fenretinimide; McN-R-1967; pharmacological studies

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vinay K. Puduvalli

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

M D Anderson Cancer Center

Houston, Texas, United States

Countries

United States

Other Identifiers

ID02-701

Identifier Type: -

Identifier Source: secondary_id

R21CA097767

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000346722

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-02566

Identifier Type: -

Identifier Source: org_study_id