Valproate and Etoposide for Patients With Neuronal Tumors and Brain Metastases

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00513162
First received: August 7, 2007
Last updated: September 18, 2012
Last verified: September 2012
  Purpose

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 Intervention Phase
Neuroectodermal Tumor
Brain Metastases
Advanced Cancer
Drug: Valproate
Drug: Etoposide
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Valproate (Valproic Acid) and Etoposide for Patients With Progressive, Relapsed or Refractory Neuronal Tumors and Brain Metastases

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Individual Maximal Tolerated Doses (iMTD) [ Time Frame: Continuous assessment and determination of dose-limiting toxicities with each dose level (increasing dose weekly) ] [ Designated as safety issue: No ]

Enrollment: 8
Study Start Date: July 2007
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Show Detailed Description

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00513162

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Tribhawan S Vats, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00513162     History of Changes
Other Study ID Numbers: 2007-0370
Study First Received: August 7, 2007
Last Updated: September 18, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Advanced Cancers
Brain
CNS
Neural
Pediatrics
Spinal
Neuroectodermal Tumor
Brain Metastases
Valproate
Valproic Acid
Depakene
Etoposide
VePesid

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms, Second Primary
Neuroectodermal Tumors
Brain Neoplasms
Neoplasms
Neoplastic Processes
Pathologic Processes
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Valproic Acid
Etoposide
Etoposide phosphate
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents

ClinicalTrials.gov processed this record on July 28, 2014