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

National Cancer Institute (NCI)

Status and phase: Terminated; Phase 2

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

Treatments: Other: pharmacological study; Drug: fenretinide; Other: laboratory biomarker analysis; Procedure: therapeutic conventional surgery

Study type: Interventional

Funder types: NIH

Identifiers

NCT00075491

CDR0000346722 (Registry Identifier)

NCI-2012-02566

R21CA097767 (U.S. NIH Grant/Contract)

ID02-701

Details and patient eligibility

About

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

Full 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.

Enrollment: 42 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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42 participants in 2 patient groups

Arm I (fenretinide, surgery)

Experimental group

Description:

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

Treatment:

Procedure: therapeutic conventional surgery

Drug: fenretinide

Other: pharmacological study

Other: laboratory biomarker analysis

Arm II (surgery)

Active Comparator group

Description:

Patients undergo surgical resection.

Treatment:

Procedure: therapeutic conventional surgery

Other: pharmacological study

Other: laboratory biomarker analysis