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.
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
- Conditions the study is for
- Brain and Central Nervous System Tumors, Unspecified Childhood Solid Tumor, Protocol Specific
- 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
Canada2 sites
Hopital Sainte Justine
Montreal, Quebec, H3T 1C5
Hospital for Sick Children
Toronto, Ontario, M5G 1X8
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.
- Conditions
- Brain and Central Nervous System Tumors, Unspecified Childhood Solid Tumor, Protocol Specific
- 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 group | Role | What they receive |
|---|---|---|
| Treatment 1 | Experimental | VPA Target Trough Concentration 75-100 mcg/mL, week 1 VPA dose: 15 mg/kg/day, divided tid Receives: Drug: valproic acid |
| Treatment 10 | Experimental | VPA Target Trough Concentration 100-150 mcg/mL, week 1 VPA dose: 15 mg/kg/day, divided tid Receives: Drug: valproic acid |
| Treatment 20 | Experimental | VPA 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.
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.
- First posted6 Apr 2005 (estimated)
- Study startMay 2005
- Primary completionOct 2007
- Study completionMar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Brain and Central Nervous System TumorsStudies of the same condition, open and under way.
- More trials run by Children's Oncology GroupThe 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
- Randomised
- Intervention model
- Single group
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Jack M. Su, MD, Study chair, Texas Children's Cancer CenterHeidi V. Russell, MD, Study chair, Texas Children's Cancer Center
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
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Valproic Acid in Children With Recurrent/Progressive Solid Tumors Including CNS Tumors
- ClinicalTrials.gov ID
- NCT00107458
- Acronym / sponsor ID
- ADVL0419
- Conditions
- Brain and Central Nervous System Tumors, Unspecified Childhood Solid Tumor, Protocol Specific
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Children's Oncology GroupResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- May 2005
- Primary completion
- Oct 2007 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 6 Apr 2005 (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.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Treatment 1 | Experimental | Drug: valproic acidVPA Target Trough Concentration 75-100 mcg/mL, week 1 VPA dose: 15 mg/kg/day, divided tid |
| Treatment 10 | Experimental | Drug: valproic acidVPA Target Trough Concentration 100-150 mcg/mL, week 1 VPA dose: 15 mg/kg/day, divided tid |
| Treatment 20 | Experimental | Drug: valproic acidVPA Target Trough Concentration 150-200 mcg/mL |
Who may qualify
- Ages
- 2 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
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 |
|---|---|---|
| valproic acid | Drug | Treatment 1, Treatment 10, Treatment 20 |
Primary outcome
Efficacy of oral etoposide at 50 mg/m2/day given concurrently with radiotherapy
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 7 Aug 2014.
- Results publication: PubMed 21115653Su 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.
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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.
Jack M. Su, MD study chair
Texas Children's Cancer Center
Heidi V. Russell, MD study chair
Texas Children's Cancer Center
17 sites in 2 countries: see every site and its status.
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.