Valproate and Etoposide for Patients With Neuronal Tumors and Brain Metastases

NCT00513162 | Completed Phase 1

• 1 other identifier: 2007-0370
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Neuroectodermal Tumor; Brain Metastases; Advanced Cancer

Keywords

Advanced Cancers; Brain; CNS; Neural; Pediatrics; Spinal; Neuroectodermal Tumor; Brain Metastases; Valproate; Valproic Acid; Depakene; Etoposide; VePesid

Outcome Measures

Primary Outcomes (1)

• Individual Maximal Tolerated Doses (iMTD)

  Continuous assessment and determination of dose-limiting toxicities with each dose level (increasing dose weekly)

Study Arms (1)

Valproate + Etoposide

EXPERIMENTAL

Valproate Starting Dose of 10 mg/kg By Mouth Daily. Etoposide 25 - 50 mg/m\^2 By Mouth Daily.

Drug: Valproate; Drug: Etoposide

Interventions

Valproate DRUG

Starting Dose of 10 mg/kg By Mouth Daily

Also known as: Valproic Acid, Depakene

Valproate + Etoposide

Etoposide DRUG

25 - 50 mg/m\^2 By Mouth Daily

Also known as: VePesid

Valproate + Etoposide

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diseases: Diagnosis of a neuroectodermal tumor of the central or peripheral nervous system or a brain metastasis.
• Disease confirmation: Patients must have a diagnosis of a malignant tumor proven by the diagnostic method considered standard of care for the specific tumor.
• Disease progression and treatment failure: Patient must have failed standard front-line treatment and must not be eligible for any higher-priority therapy.
• Negative pregnancy test for female patients between menarche and menopause is required.
• Patients must sign an informed consent indicating that they are aware of the investigational nature of this study in keeping with the policies of the hospital.
• Approval for the use of this treatment regimen by the individual's Human Rights Committee or Institutional Review Board (IRB) must be obtained in accordance with the individual institutional policies and the local, state, and national rules, regulations and laws, is mandatory for an enrolling institution. The documentation of this approval must be on file at the MDAnderson Cancer Center Pediatric Oncology Trials Office prior to enrollment of any patient on study.

You may not qualify if:

• Neurofibromatosis type I.
• Known or suspected inborn errors of metabolism.
• Patients who require any of the following medications are excluded from enrollment: Carbamazepine, Oxcarbazepine, Primidone, Phenobarbital, Topiramate, Carbapenem antibiotics (ertapenem, imipenem, meropenem), Felbamate, Isoniazid, Lamotrigine, Macrolide antibiotics (clarithromycin, erythromycin, troleandomycin, azithromycin), Zidovudine, Risperidone, Salicylates.
• Patients who take antiviral medications usually targeted to treat HIV infections or have clinical signs for acquired immunodeficiency syndrome (AIDS) are excluded. HIV testing is not mandatory.
• Patients who had previous chemotherapy less than three weeks (21 days) ago cannot be enrolled: Patients must have been off all previous chemotherapy or radiotherapy for the 3 weeks prior to initiation of study treatment and recovered from toxic effects of that therapy.
• Patients which are on a stable dose for valproic acid prior to enrolment are not eligible.
• Patients which have been treated with valproic acid or other histone deacetylase inhibitors such as SAHAa or MS275 and the treatment has failed to control the tumor are not eligible.
• Patient which have been treated with oral continuous etoposide previously and the treatment has failed to control the tumor are not eligible.
• White blood cell count below 2,000/µL excludes patient from enrollment.
• Absolute neutrophil count below 700/uL excludes patient from enrollment.
• Platelet count below 80,000 excludes patient from enrollment.
• Pancreatitis with amylase above two times the upper normal limit excludes patient from enrollment, (even in the absence of clinical signs of pancreatitis).
• Somnolence at daytime for more than 6 hours excludes patient from enrollment
• Bilirubin total \> 1.5 mg/dL excludes patient from enrollment.
• ALT \> 2.5 times upper normal value excludes patient from enrollment.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• The University of Texas M.D.Anderson Cancer Center

MeSH Terms

Conditions

Neuroectodermal Tumors; Brain Neoplasms

Interventions

Valproic Acid; Etoposide

Condition Hierarchy (Ancestors)

Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Tribhawan S Vats, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2007
• First Posted: August 8, 2007
• Study Start: July 1, 2007
• Primary Completion: September 1, 2012
• Last Updated: September 19, 2012

Record last verified: 2012-09

Locations

US (1)