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Brain and Central Nervous System TumorsPhase 1NCT00107458

Valproic Acid in Treating Young Patients With Recurrent or Refractory Solid Tumors or CNS Tumors

A Phase 1 study testing valproic acid in people with Brain and Central Nervous System Tumors and Unspecified Childhood Solid Tumor, Protocol Specific, run by Children's Oncology Group at 17 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

RATIONALE: Drugs used in chemotherapy, such as valproic acid, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Valproic acid may also stop the growth of solid tumors or CNS tumors by blocking blood flow to the tumor. Read more about this study

Who is it for?
Ages 2 to 21 years
What is being tested?
valproic acid
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
17 sitesin 2 countries
Study dates
May 2005to Mar 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 2 to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

DISEASE CHARACTERISTICS:

  • Histologically confirmed* malignant solid tumor, including CNS tumors, at original diagnosis or relapse
  • Recurrent or refractory disease NOTE: *Histologic confirmation not required for intrinsic brain stem or optic pathway tumors
  • Measurable or evaluable disease, defined by 1 of the following criteria:
  • Any unidimensionally measurable lesion ≥ 10 mm by standard MRI or CT scan for either solid or CNS tumors
  • At least 1 nonmeasurable lesion that is evaluable by nuclear medicine, immunocytochemistry, tumor markers, cerebrospinal fluid cytology, or other reliable measures
  • No known curative therapy exists
  • No documented tumor involvement in the bone marrow

PATIENT CHARACTERISTICS:

Age

  • 2 to 21

Performance status*

  • Lansky 50-100% (for patients ≤ 10 years of age)
  • Karnofsky 50-100% (for patients > 10 years of age)

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count ≥ 1,000/mm^3
  • Platelet count ≥ 100,000/mm^3 (transfusion independent)
  • Hemoglobin ≥ 8.0 g/dL (transfusions allowed)

Hepatic

  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT ≤ 110 (ULN for this study is 45 U/L)
  • Albumin ≥ 2 g/dL

Renal

  • Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR
  • Creatinine based on age as follows:
  • No greater than 0.8 mg/dL (for patients ≤ 5 years of age)
  • No greater than 1.0 mg/dL (for patients 6 to 10 years of age)
  • No greater than 1.2 mg/dL (for patients 11 to 15 years of age)
  • No greater than 1.5 mg/dL (for patients over 15 years of age)

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Neurologic deficits in patients with CNS tumors must be stable for ≥ 1 week before study entry
  • No uncontrolled infection
  • No known urea cycle disorders or other metabolic disorders
  • No other condition that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Recovered from prior immunotherapy
  • At least 7 days since prior hematopoietic growth factors that support platelet or WBC number or function
  • At least 7 days since prior antineoplastic biologic agents
  • At least 3 months since prior stem cell transplantation or rescue without total body irradiation
  • No evidence of active graft vs host disease
  • No other concurrent anticancer biologic therapy or immunotherapy

Chemotherapy

  • More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) and recovered
  • No other concurrent anticancer chemotherapy

Endocrine therapy

  • Patients with CNS tumors must be on a stable or decreasing dose of dexamethasone for the past 7 days

Radiotherapy

  • See Biologic therapy
  • Recovered from prior radiotherapy
  • At least 6 months since prior total body irradiation, craniospinal radiotherapy, or radiotherapy to ≥ 50% of the pelvis
  • At least 6 weeks since other prior substantial bone marrow radiotherapy
  • At least 2 weeks since prior local palliative small port radiotherapy
  • No concurrent anticancer radiotherapy

Surgery

  • Not specified

Other

  • No other concurrent investigational agents
  • No other concurrent anticancer agents
  • No other concurrent anticonvulsants
  • Patients receiving valproic acid (VPA) before study entry must have a total trough VPA concentration < 100 mcg/mL within the past 7 days

Trial locations and contacts

17 sites in 2 countries.

17 sites in 2 countries

United States15 sites
  • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Children's Memorial Hospital - Chicago

    Chicago, Illinois, 60614

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229-3039

  • Baylor University Medical Center - Houston

    Houston, Texas, 77030-2399

  • Indiana University Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202-5289

  • University of Minnesota Children's Hospital - Fairview

    Minneapolis, Minnesota, 55455

  • Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

    New York, New York, 10032

  • Children's Hospital of Orange County

    Orange, California, 92868

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104-9786

  • Oregon Health & Science University Cancer Institute

    Portland, Oregon, 97239-3098

  • Mayo Clinic Cancer Center

    Rochester, Minnesota, 55905

  • Children's Hospital and Regional Medical Center - Seattle

    Seattle, Washington, 98105

  • Stanford Comprehensive Cancer Center - Stanford

    Stanford, California, 94305

  • SUNY Upstate Medical University Hospital

    Syracuse, New York, 13210

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010-2970

Other trials in United States

Canada2 sites
  • Hopital Sainte Justine

    Montreal, Quebec, H3T 1C5

  • Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

Other trials in Canada

About this study

Official title: A Phase I Study of Valproic Acid in Children With Recurrent/Progressive Solid Tumors Including CNS Tumors

RATIONALE: Drugs used in chemotherapy, such as valproic acid, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Valproic acid may also stop the growth of solid tumors or CNS tumors by blocking blood flow to the tumor.

PURPOSE: This phase I trial is studying the side effects and best dose of valproic acid in treating patients with recurrent or refractory solid tumors or CNS tumors.

Read the detailed description

OBJECTIVES:

Primary

  • Determine the toxic effects of valproic acid (VPA) administered at doses required to maintain serum trough VPA concentrations of 100-150 mcg/mL or 150-200 mcg/mL in young patients with recurrent or refractory solid tumors or CNS tumors.

Secondary

  • Determine the steady-state serum trough concentration of free and total VPA at the targeted total trough VPA concentration in these patients.
  • Determine the steady state histone acetylation status of peripheral blood monocytes at the targeted trough VPA concentration in these patients.
  • Determine the pharmacokinetic profile of this drug in these patients.
  • Correlate histone acetylation with free or total trough VPA concentration in these patients.
  • Determine, preliminarily, the antitumor activity of this drug in these patients.

OUTLINE: This is a dose-escalation, multicenter study.

For course 1, patients receive escalating doses of oral valproic acid (VPA) twice daily until a target serum trough VPA concentration range is maintained for 28 days. Patients who achieve the target serum trough VPA concentration range receive subsequent courses of oral VPA twice daily (at the dose found to maintain the target serum trough VPA concentration range) on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

The first cohort of 6 patients receives VPA to achieve an initial target trough serum VPA concentration. If fewer than 2 of 6 patients in the first cohort experience dose-limiting toxicity (DLT), then a second cohort of 6 patients receives VPA to achieve the next higher target trough serum VPA concentration. If fewer than 2 patients from the second cohort experience DTL, then 6 additional patients are enrolled in this cohort to better define pharmacokinetics and DLT at this VPA concentration range.

After completion of study treatment, patients are followed annually.

PROJECTED ACCRUAL: A total of 12-18 patients will be accrued for this study.

Being tested
valproic acid
Keywords
recurrent childhood brain stem glioma, recurrent childhood brain tumor, recurrent childhood cerebellar astrocytoma, recurrent childhood cerebral astrocytoma, recurrent childhood ependymoma, recurrent childhood medulloblastoma, recurrent childhood supratentorial primitive neuroectodermal tumor, unspecified childhood solid tumor, protocol specific, recurrent childhood visual pathway and hypothalamic glioma, childhood high-grade cerebral astrocytoma, childhood low-grade cerebral astrocytoma, childhood infratentorial ependymoma, childhood supratentorial ependymoma, childhood spinal cord neoplasm, childhood grade I meningioma, childhood grade II meningioma, childhood grade III meningioma, childhood craniopharyngioma, childhood central nervous system germ cell tumor
Medical subject headings
Central Nervous System Neoplasms, Astrocytoma, Familial ependymoma, Medulloblastoma, Optic Nerve Glioma, Spinal Cord Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • valproic acidDrug

Study groups in NCT00107458
Study groupRoleWhat they receive
Treatment 1ExperimentalVPA Target Trough Concentration 75-100 mcg/mL, week 1 VPA dose: 15 mg/kg/day, divided tid
Receives: Drug: valproic acid
Treatment 10ExperimentalVPA Target Trough Concentration 100-150 mcg/mL, week 1 VPA dose: 15 mg/kg/day, divided tid
Receives: Drug: valproic acid
Treatment 20ExperimentalVPA Target Trough Concentration 150-200 mcg/mL
Receives: Drug: valproic acid

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Efficacy of oral etoposide at 50 mg/m2/day given concurrently with radiotherapy

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Apr 2005 (estimated)
  2. Study startMay 2005
  3. Primary completionOct 2007
  4. Study completionMar 2012

Resources

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
Randomised
Intervention model
Single group
Masking
Single blind
Who is masked
Participant
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00107458
Sponsor's protocol ID
ADVL0419
Other IDs
COG-ADVL0419, NCI-05-C-0235, NCI-P6631, CDR0000417845
Status last verified
Aug 2014
First submitted
5 Apr 2005
Last updated
7 Aug 2014
Results posted
No
Data monitoring committee
Yes

Publications

  • Su JM, Li XN, Thompson P, Ou CN, Ingle AM, Russell H, Lau CC, Adamson PC, Blaney SM. Phase 1 study of valproic acid in pediatric patients with refractory solid or CNS tumors: a children's oncology group report. Clin Cancer Res. 2011 Feb 1;17(3):589-97. doi: 10.1158/1078-0432.CCR-10-0738. Epub 2010 Nov 29.

    PubMed 21115653

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing valproic acid in people with Brain and Central Nervous System Tumors and Unspecified Childhood Solid Tumor, Protocol Specific, run by Children's Oncology Group at 17 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

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 7 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States, Canada. 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?

Efficacy of oral etoposide at 50 mg/m2/day given concurrently with radiotherapy. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00107458, which also lists 1 linked publication.

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 7 Aug 2014.

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