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Valproate and Etoposide for Patients With Neuronal Tumors and Brain Metastases

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00513162
Recruitment Status : Completed
First Posted : August 8, 2007
Last Update Posted : September 19, 2012
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

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.

Condition or disease Intervention/treatment Phase
Neuroectodermal Tumor Brain Metastases Advanced Cancer Drug: Valproate Drug: Etoposide Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Valproate (Valproic Acid) and Etoposide for Patients With Progressive, Relapsed or Refractory Neuronal Tumors and Brain Metastases
Study Start Date : July 2007
Actual Primary Completion Date : September 2012

Arm Intervention/treatment
Experimental: Valproate + Etoposide
Valproate Starting Dose of 10 mg/kg By Mouth Daily. Etoposide 25 - 50 mg/m^2 By Mouth Daily.
Drug: Valproate
Starting Dose of 10 mg/kg By Mouth Daily
Other Names:
  • Valproic Acid
  • Depakene

Drug: Etoposide
25 - 50 mg/m^2 By Mouth Daily
Other Name: VePesid

Primary Outcome Measures :
  1. Individual Maximal Tolerated Doses (iMTD) [ Time Frame: Continuous assessment and determination of dose-limiting toxicities with each dose level (increasing dose weekly) ]

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Diseases: Diagnosis of a neuroectodermal tumor of the central or peripheral nervous system or a brain metastasis.
  2. Disease confirmation: Patients must have a diagnosis of a malignant tumor proven by the diagnostic method considered standard of care for the specific tumor.
  3. Disease progression and treatment failure: Patient must have failed standard front-line treatment and must not be eligible for any higher-priority therapy.
  4. Negative pregnancy test for female patients between menarche and menopause is required.
  5. 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.
  6. 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.

Exclusion Criteria:

  1. Neurofibromatosis type I.
  2. Known or suspected inborn errors of metabolism.
  3. 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.
  4. 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.
  5. 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.
  6. Patients which are on a stable dose for valproic acid prior to enrolment are not eligible.
  7. 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.
  8. Patient which have been treated with oral continuous etoposide previously and the treatment has failed to control the tumor are not eligible.
  9. White blood cell count below 2,000/µL excludes patient from enrollment.
  10. Absolute neutrophil count below 700/uL excludes patient from enrollment.
  11. Platelet count below 80,000 excludes patient from enrollment.
  12. Pancreatitis with amylase above two times the upper normal limit excludes patient from enrollment, (even in the absence of clinical signs of pancreatitis).
  13. Somnolence at daytime for more than 6 hours excludes patient from enrollment
  14. Bilirubin total > 1.5 mg/dL excludes patient from enrollment.
  15. ALT > 2.5 times upper normal value excludes patient from enrollment.
  16. AST >2.5 x upper normal value excludes patients from enrollment.
  17. Frequent vomiting or medical condition that could interfere with oral medication intake (e.g., partial bowel obstruction) excludes patient from enrollment.
  18. Pregnant or nursing women cannot be enrolled.
  19. Women of childbearing potential who are not using an effective method of contraception cannot be enrolled.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00513162

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United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
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Principal Investigator: Tribhawan S Vats, MD M.D. Anderson Cancer Center
Additional Information:
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Responsible Party: M.D. Anderson Cancer Center Identifier: NCT00513162    
Other Study ID Numbers: 2007-0370
First Posted: August 8, 2007    Key Record Dates
Last Update Posted: September 19, 2012
Last Verified: September 2012
Keywords provided by M.D. Anderson Cancer Center:
Advanced Cancers
Neuroectodermal Tumor
Brain Metastases
Valproic Acid
Additional relevant MeSH terms:
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Neoplasm Metastasis
Neoplasms, Second Primary
Brain Neoplasms
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Neoplastic Processes
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neoplasms, Glandular and Epithelial
Valproic Acid
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
GABA Agents
Neurotransmitter Agents