Valproate and Etoposide for Patients With Neuronal Tumors and Brain Metastases

Advanced Cancer Clinical Trial

Official title: Valproate (Valproic Acid) and Etoposide for Patients With Progressive, Relapsed or Refractory Neuronal Tumors and Brain Metastases

Status Completed

Clinical Trial Summary

Primary Objective:

• Determine the interindividual range and median of individual maximum tolerated doses of valproic acid administered as one time evening dose in conjunction with a dose oral etoposide (50 mg/m2/day for children, but only 25mg/m2/day for adults to start) for four different age groups.

Secondary Objectives:

• Determine the qualitative and quantitative toxicity and reversibility of toxicity of valproic acid in conjunction with oral etoposide,

• To investigate the clinical pharmacokinetics of valproic acid when given in conjunction with oral etoposide,

• To describe quality of life of patients with relapsed, or progressive central and peripheral nervous system tumors when treated with oral valproic acid and etoposide,

• To observe and describe the response pattern of progressive central nervous system tumors treated with oral valproic acid and etoposide,

• To observe and describe event free survival time and overall survival time of patients with relapsed, or progressive central nervous system tumors when treated with oral valproic acid and etoposide,

• To determine if histone deacetylase activity and topoisomerase expression in lymphocytes of patients is related to valproic acid levels, and

• To determine, if the individual maximal tolerated dose (iMTD) depends on the initial performance status of the patient in the beginning of the treatment.

Clinical Trial Description

Study Drugs:

Etoposide is designed to block cell growth by breaking the DNA, which may cause the cells to die.

Valproic acid was first designed as an anti-seizure medication. It was also found to change cancer cells and make them more sensitive to etoposide.

Screening Tests:

Before you start treatment on this study, you will have "screening tests". These tests help your doctor decide if you are eligible to take part in this study.

• Your medical history will be reviewed.

• You will have a physical exam.

• You will be asked how well you are able to perform the normal activities of daily living (performance status evaluation).

• You will complete a questionnaire about your activities or daily living. The questionnaire will take about 5 to 10 minutes to complete.

• Blood (about 2-3 tablespoons) will be drawn for routine tests. This routine blood draw may include a pregnancy test for women who are able to have children. To be eligible to take part in this study, the pregnancy test must be negative.

• Urine may be collected to check for metabolic disease. This urine sample may include a pregnancy test for women who are able to have children. To be eligible to take part in this study, the pregnancy test must be negative.

• You will have a magnetic resonance imaging (MRI) or computed tomography (CT) scan.

• If your doctor thinks it is necessary, you may have additional blood and/or urine tests.

Dose Escalation:

When you begin the study, you will begin receiving the lowest dose level of valproic acid. Every week, the dose will be increased. This will continue until the maximum tolerated dose (MTD) is found. Once the MTD is found, you will continue to receive that dose level of valproic acid while you are on study. However, if your doctor thinks it is necessary, this dose level could be lowered.

If you are a child (less than or equal to 18 years of age), the amount of etoposide that you take while on study will not change.

If you are an adult (more than 18 years of age), your will receive a low dose of etoposide while the MTD of valproic acid is being found. After the MTD of valproic acid is found, your dose of etoposide will be increased every week until the MTD is found. However, if your doctor thinks it is necessary, this dose level could be lowered.

Study Drug Administration:

You will receive valproic acid and etoposide every evening in pill form.

If you have difficulty swallowing the pills, etoposide can be given in the evening in liquid form. Valproic acid can be given in liquid form, divided in 2 doses per day, 1 in the morning and 1 in the evening.

Study Visits During Dose Escalation:

While your valproic acid or etoposide medication is being increased, every week you will have a physical exam and blood (about 2-3 tablespoons)and urine will be collected for routine tests.

Every other month, you will have CT or MRI scans to check the status of the disease. You may have these tests and procedures more often if your doctor thinks it is necessary.

Study Visits After Maximum Tolerated Dose (MTD):

Every month, you will have a physical exam, and blood (about 2-3 tablespoons) and urine will be collected for routine tests.

Every other month, you will have CT or MRI scans to check the status of the disease.

Every 6 months, a portion of the blood or urine collected for routine tests will be used for a pregnancy test for women who are able to have children.

-You may have these tests and procedures more often if your doctor thinks it is necessary.

Length of Study:

You may remain on study for up to 2 years. You will be taken off study if the disease gets worse or intolerable side effects occur.

End-of-Study Visit:

Once you are off study, you will have an end-of-study visit. At this visit, the following tests and procedures will be performed:

• You will have a physical exam.

• Blood (about 2-3 tablespoons) and urine will be collected for routine tests.

• If your doctor thinks it is necessary, you will have a CT or MRI to check the status of the disease.

Follow-Up:

Once you are off study, you will be contacted by telephone once a year to check the status of the disease. The phone call will take 2-3 minutes.

This is an investigational study. Etoposide is FDA approved and commercially available. Valproic acid is FDA approved and commercially available for the treatment of seizures. The use of these drugs together is investigational. Up to 120 patients will take part in this multicenter study. Up to 100 will be enrolled at M. D. Anderson. ;

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Cancer
• Brain Metastases
• Brain Neoplasms
• Neoplasm Metastasis
• Neuroectodermal Tumor
• Neuroectodermal Tumors
• Neuroectodermal Tumors, Primitive

• NCT number: NCT00513162
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Status: Completed
• Phase: Phase 1
• Start date: July 2007