Brain NeoplasmsPhase 1NCT00001565
Phase I and Pharmacokinetic Trial of Phenylbutyrate Given as a Continuous Infusion in Pediatric Patients With Refractory Malignancy
A Phase 1 study testing phenylbutyrate in people with Brain Neoplasms and Neuroblastoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This is a pharmacokinetic trial. Patients receive phenylbutyrate through a central venous catheter for each 28 day cycle. The first several days of drug administration should be inpatient. Cycles may be repeated if there is no tumor progression or dose limiting toxicities (DLT). There are no breaks between cycles. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Brain Neoplasms, Neuroblastoma
- What is being tested?
- phenylbutyrate
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 1996to Oct 2000
- 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
Disease Characteristics:
Histologically proven cancer that is refractory to standard therapy.
Patients with neurofibromatosis having progressive inoperable plexiform neurofibromas with potential to cause significant morbidity are eligible.
Patients with brainstem gliomas histology may have histology requirements waived.
Patients without prior therapy are eligible if they have diseases with no available standard therapy.
Patients with evidence of bone marrow involvement by tumor, or a history of either bone marrow transplantation or extensive radiotherapy will be eligible, but inevaluable for hematologic toxicities.
Patients with greater than grade 2 neurocortical toxicity will be excluded.
PRIOR/CONCURRENT THERAPY:
Biologic Therapy: No concurrent hematopoietic growth factor.
Chemotherapy: No chemotherapy within 3 weeks of study.
No nitrosoursea within 6 weeks of study.
No concurrent chemotherapy allowed.
Must be on stable or decreasing dose of dexamethasone within 2 weeks of study.
Endocrine Therapy: Not specified.
Radiotherapy: No radiotherapy within 6 weeks of study.
Surgery: Not specified.
Other:
Patient must be recovered from toxic effects of all prior therapy.
Concurrent antibiotic therapy when appropriate.
Patient Characteristics:
Age: 2 to 21.
Performance Status: ECOG 0-2.
Life Expectancy: At least 8 weeks.
Hematopoietic (hematologic requirements below do not apply to patients with histologically confirmed bone marrow involvement or history of either bone marrow transplantation or extensive radiotherapy; these patients are inevaluable for hematologic toxicity):
Absolute granulocyte count (AGC) at least 1500/mm3.
Platelet count at least 100,000/mm3.
Hemoglobin at least 8 g/dL.
Hepatic:
Bilirubin no greater than 2 mg/Dl.
SGPT less than 2 times normal.
Renal:
Creatinine no greater than 1.5 mg/Dl OR
Creatinine clearance at least 60 Ml/min/square meter.
Other:
No systemic illness.
Not pregnant or nursing.
No amino acidurias or organic acidemias.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Cancer Institute (NCI)
Bethesda, Maryland, 20892
About this study
This is a pharmacokinetic trial. Patients receive phenylbutyrate through a central venous catheter for each 28 day cycle. The first several days of drug administration should be inpatient. Cycles may be repeated if there is no tumor progression or dose limiting toxicities (DLT). There are no breaks between cycles.
Once a minimum of 3 patients have completed at least 4 weeks of therapy without DLT, new patients will be entered at the next dose level.
Read the detailed description
Phenylbutyrate is an aromatic fatty acid that is converted to phenylacetate in vivo by mitochondrial beta-oxidation to phenylacetate. Preclinical studies have shown that continuous exposure to phenylacetate or phenylbutyrate can induce tumor cytostasis and differentiation in a wide variety of cell lines including malignant gliomas and neuroblastomas. However, phenylbutyrate has been shown to be a more potent differentiating agent than phenylacetate in a variety of tumor cell lines. In addition, phenylbutyrate appears to have molecular activities that are distinct from phenylacetate. The objective of this trial is to determine the maximum tolerated dose and the toxicities of phenylbutyrate administered as a continuous intravenous infusion for 28 days. In addition, the pharmacokinetics of phenylbutyrate and its metabolite, phenylacetate, will be studied using both model-dependent and model-independent parameters.
- Conditions
- Brain Neoplasms, Neuroblastoma
- Being tested
- phenylbutyrate
- Keywords
- Brain Tumors, Differentiation, Maximally Tolerated Dose, Neuroblastoma, Phenylacetate
- Medical subject headings
- Brain Neoplasms, Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
phenylbutyrateDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2002 (estimated)
- Study startDec 1996
- Study completionOct 2000
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Brain NeoplasmsStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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
- Enrolment
- 35 participants
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001565
- Sponsor's protocol ID
- 970051
- Other IDs
- 97-C-0051
- Status last verified
- Nov 1999
- First submitted
- 3 Nov 1999
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Samid D, Shack S, Myers CE. Selective growth arrest and phenotypic reversion of prostate cancer cells in vitro by nontoxic pharmacological concentrations of phenylacetate. J Clin Invest. 1993 May;91(5):2288-95. doi: 10.1172/JCI116457.
PubMed 8486788Samid D, Ram Z, Hudgins WR, Shack S, Liu L, Walbridge S, Oldfield EH, Myers CE. Selective activity of phenylacetate against malignant gliomas: resemblance to fetal brain damage in phenylketonuria. Cancer Res. 1994 Feb 15;54(4):891-5.
PubMed 8313377Samid D, Shack S, Sherman LT. Phenylacetate: a novel nontoxic inducer of tumor cell differentiation. Cancer Res. 1992 Apr 1;52(7):1988-92.
PubMed 1372534
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I and Pharmacokinetic Trial of Phenylbutyrate Given as a Continuous Infusion in Pediatric Patients With Refractory Malignancy
- ClinicalTrials.gov ID
- NCT00001565
- Acronym / sponsor ID
- 970051
- Conditions
- Brain Neoplasms, Neuroblastoma
- Keywords
- Brain Tumors, Differentiation, Maximally Tolerated Dose, Neuroblastoma, Phenylacetate
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Dec 1996
- Study completion
- Oct 2000
- First posted
- 10 Dec 2002 (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.
This is a pharmacokinetic trial. Patients receive phenylbutyrate through a central venous catheter for each 28 day cycle. The first several days of drug administration should be inpatient. Cycles may be repeated if there is no tumor progression or dose limiting toxicities (DLT). There are no breaks between cycles.
Once a minimum of 3 patients have completed at least 4 weeks of therapy without DLT, new patients will be entered at the next dose level.
Detailed description
Phenylbutyrate is an aromatic fatty acid that is converted to phenylacetate in vivo by mitochondrial beta-oxidation to phenylacetate. Preclinical studies have shown that continuous exposure to phenylacetate or phenylbutyrate can induce tumor cytostasis and differentiation in a wide variety of cell lines including malignant gliomas and neuroblastomas. However, phenylbutyrate has been shown to be a more potent differentiating agent than phenylacetate in a variety of tumor cell lines. In addition, phenylbutyrate appears to have molecular activities that are distinct from phenylacetate. The objective of this trial is to determine the maximum tolerated dose and the toxicities of phenylbutyrate administered as a continuous intravenous infusion for 28 days. In addition, the pharmacokinetics of phenylbutyrate and its metabolite, phenylacetate, will be studied using both model-dependent and model-independent parameters.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older 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 |
|---|---|---|
| phenylbutyrate | Drug | – |
Primary outcome
Not reported in the source record.
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 4 Mar 2008.
- Background: PubMed 8486788Samid D, Shack S, Myers CE. Selective growth arrest and phenotypic reversion of prostate cancer cells in vitro by nontoxic pharmacological concentrations of phenylacetate. J Clin Invest. 1993 May;91(5):2288-95. doi: 10.1172/JCI116457.
- Background: PubMed 8313377Samid D, Ram Z, Hudgins WR, Shack S, Liu L, Walbridge S, Oldfield EH, Myers CE. Selective activity of phenylacetate against malignant gliomas: resemblance to fetal brain damage in phenylketonuria. Cancer Res. 1994 Feb 15;54(4):891-5.
- Background: PubMed 1372534Samid D, Shack S, Sherman LT. Phenylacetate: a novel nontoxic inducer of tumor cell differentiation. Cancer Res. 1992 Apr 1;52(7):1988-92.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 phenylbutyrate in people with Brain Neoplasms and Neuroblastoma, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. 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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00001565, which also lists 3 linked publications.
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 4 Mar 2008.