Neuroectodermal TumorPhase 1NCT00513162
Valproate and Etoposide for Patients With Neuronal Tumors and Brain Metastases
A Phase 1 study testing Valproate and Etoposide in people with Neuroectodermal Tumor and Brain Metastases, run by M.D. Anderson Cancer Center at 1 site in United States.
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Neuroectodermal Tumor, Brain Metastases, Advanced Cancer
- What is being tested?
- Valproate and Etoposide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2007to Sep 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 19Show fewer
- 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.
- AST >2.5 x upper normal value excludes patients from enrollment.
- Frequent vomiting or medical condition that could interfere with oral medication intake (e.g., partial bowel obstruction) excludes patient from enrollment.
- Pregnant or nursing women cannot be enrolled.
- Women of childbearing potential who are not using an effective method of contraception cannot be enrolled.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Valproate (Valproic Acid) and Etoposide for Patients With Progressive, Relapsed or Refractory Neuronal Tumors and Brain Metastases
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.
Read more
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.
Read the detailed 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.
- Conditions
- Neuroectodermal Tumor, Brain Metastases, Advanced Cancer
- Being tested
- Valproate, Etoposide
- Keywords
- Advanced Cancers, Brain, CNS, Neural, Pediatrics, Spinal, Neuroectodermal Tumor, Brain Metastases, Valproate, Valproic Acid, Depakene, Etoposide, VePesid
- Medical subject headings
- Neuroectodermal Tumors, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ValproateDrug
Also called Valproic Acid, Depakene
Starting Dose of 10 mg/kg By Mouth Daily
EtoposideDrug
Also called VePesid
25 - 50 mg/m^2 By Mouth Daily
| Study group | Role | What they receive |
|---|---|---|
| Valproate + Etoposide | Experimental | Valproate Starting Dose of 10 mg/kg By Mouth Daily. Etoposide 25 - 50 mg/m^2 By Mouth Daily. Receives: Drug: Valproate; Drug: Etoposide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Individual Maximal Tolerated Doses (iMTD)
Measured: Continuous assessment and determination of dose-limiting toxicities with each dose level (increasing dose weekly)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2007 (estimated)
- Study startJul 2007
- Primary completionSep 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neuroectodermal TumorStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tribhawan S Vats, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00513162
- Sponsor's protocol ID
- 2007-0370
- Status last verified
- Sep 2012
- First submitted
- 7 Aug 2007
- Last updated
- 19 Sep 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Valproate (Valproic Acid) and Etoposide for Patients With Progressive, Relapsed or Refractory Neuronal Tumors and Brain Metastases
- ClinicalTrials.gov ID
- NCT00513162
- Acronym / sponsor ID
- 2007-0370
- Conditions
- Neuroectodermal Tumor, Brain Metastases, Advanced Cancer
- Keywords
- Advanced Cancers, Brain, CNS, Neural, Pediatrics, Spinal, Neuroectodermal Tumor, Brain Metastases
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- Jul 2007
- Primary completion
- Sep 2012 (actual)
- First posted
- 8 Aug 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Valproate + Etoposide | Experimental | Drug: Valproate, Drug: EtoposideValproate Starting Dose of 10 mg/kg By Mouth Daily. Etoposide 25 - 50 mg/m^2 By Mouth Daily. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ValproateAlso: Valproic Acid, DepakeneStarting Dose of 10 mg/kg By Mouth Daily | Drug | Valproate + Etoposide |
| EtoposideAlso: VePesid25 - 50 mg/m^2 By Mouth Daily | Drug | Valproate + Etoposide |
Primary outcome
Individual Maximal Tolerated Doses (iMTD)
Time frame: Continuous assessment and determination of dose-limiting toxicities with each dose level (increasing dose weekly)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2012.
- The University of Texas M.D.Anderson Cancer CenterLink provided by the sponsor.
Related trials for Neuroectodermal Tumor
Active, not recruitingPhase 1/2
Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
Low Grade Glioma, Recurrent Childhood Pilocytic Astrocytoma
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 1
IL-17 Blockade to Decrease irAEs (REPLAY)
Metastatic Melanoma
RecruitingPhase 2
A UGT1A1 Genotype-Directed Study of Belinostat Pharmacokinetics and Toxicity
Carcinoma, Neuroendocrine, Tumor, Neuroendocrine
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tribhawan S Vats, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Valproate and Etoposide in people with Neuroectodermal Tumor and Brain Metastases, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Sep 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Individual Maximal Tolerated Doses (iMTD) (time frame: Continuous assessment and determination of dose-limiting toxicities with each dose level (increasing dose weekly)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2012.