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Adult Anaplastic AstrocytomaPhase 1NCT01378481

High-Dose Vorinostat and Fractionated Stereotactic Body Radiation Therapy in Treating Patients With Recurrent Glioma

A Phase 1 study testing Vorinostat, Stereotactic Radiosurgery and Laboratory Biomarker Analysis in people with Adult Anaplastic Astrocytoma and Adult Anaplastic Oligodendroglioma, run by National Cancer Institute (NCI) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This study is being done to determine if an investigational cancer treatment called vorinostat combined with fractionated stereotactic radiation therapy (FSRT) is effective in treating recurrent high grade gliomas. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Vorinostat, Stereotactic Radiosurgery and Laboratory Biomarker Analysis
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteUnited States
Study dates
Jun 2012to Aug 2013
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have a previously histologically or cytologically confirmed glioma (astrocytic or oligodendroglial supratentorial tumors grades 3 or 4 according to the World Health Organization [WHO] 2007 classification) that has been previously treated with fractionated radiation therapy and now shows evidence of recurrence
  • Patients must have recovered from the toxic effects of prior therapy
  • Patients must have recovered from the effects of any prior surgery to any part of the body; there must be a minimum of 28 days from the day of surgery to the day of registration; for core or needle biopsy, a minimum of 7 days must have elapsed prior to registration
  • Patients may have previously undergone more than one craniotomy
  • Prior treatment with cytotoxic and biological agents is permissible; there should be at least a 2 week break between prior treatment and enrollment; (in the case of bevacizumab, since this trial involves surgery, at least 4 weeks should elapse between last dose of drug and enrollment, in the case of nitrosoureas or mitomycin C, at least 6 weeks)
  • Prior treatment with fractionated radiation therapy (up to 60 Gray [Gy]) is an eligibility criterion, however this should have been completed >= 4 weeks prior to enrollment and there should not have been a second course of fractionated radiotherapy to the supratentorial area
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  • One prior single fraction radiosurgical procedure within the treatment field is acceptable if V12 < 5 cc (V12 is the volume of brain receiving 12 or more Gy); additional radiosurgical procedures outside of the treatment area are acceptable
  • Patients should not have received prior histone deacetylase therapy (HDAC) therapy, an exception being the anti-seizure medicine valproic acid; however even valproic acid should not be given concurrently with vorinostat
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Life expectancy of greater than 2 months
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
  • Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Prothrombin time/international normalized ratio (PT INR) < 1.4 for patients not on warfarin
  • Women of childbearing potential must have a negative beta-human chorionic gonadotropin (HCG) pregnancy test documented within 7 days prior to registration
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; the effects of vorinostat on the developing human fetus are unknown; HDAC inhibitor agents as well as the ionizing radiation used in this trial are known to be teratogenic; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • Patients who have had:
  • Radiotherapy within 4 weeks
  • Chemotherapy/biological agents (excluding bevacizumab, nitrosoureas and mitomycin C) within 2 weeks
  • Bevacizumab within 4 weeks
  • Nitrosoureas and mitomycin C within 6 weeks prior to entering the study
  • Those who have not recovered from acute adverse events due to any prior therapeutic agents
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  • Patients may not be receiving any other investigational agents
  • Evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of >= 2 mm using the analysis of an electrocardiogram (EKG) performed within 14 days of registration
  • A history of long QT syndrome, or corrected QTc (QTc) prolongations > 470 ms at baseline
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat or other HDAC inhibitor or other agents used in study
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because vorinostat is an antineoplastic agent with the potential for teratogenic or abortifacient effects, class D; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with vorinostat, breastfeeding should be discontinued if the mother is treated with vorinostat; these potential risks may also apply to other agents used in this study

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

Other trials in United States

About this study

Official title: High-Dose Vorinostat With Radiation Therapy in the Treatment of Recurrent Glioma

This study is being done to determine if an investigational cancer treatment called vorinostat combined with fractionated stereotactic radiation therapy (FSRT) is effective in treating recurrent high grade gliomas. The main goal of this research study is to determine the highest dose of vorinostat that can be given to patients with recurrent tumors. The study will also determine the potential side effects and safety of these treatment combinations. Vorinostat is a small molecule inhibitor of histone deacetylase (HDAC). HDAC inhibitors help unravel the deoxyribonucleic acid (DNA) of the cancer cells and make them more susceptible to the treatment with radiation.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the phase II dose when intermittent short-course vorinostat is combined with fractionated radiation therapy in recurrent high-grade glioma.

SECONDARY OBJECTIVES:

  1. Define the pharmacokinetics of vorinostat entry into the cerebrospinal fluid (CSF) and demonstrate that vorinostat influences glioma biology.

OUTLINE: This is a dose-escalation study of vorinostat.

Patients receive high-dose vorinostat orally (PO) at 48, 27, and 3 hours prior to surgery. Beginning 2-6 weeks later, patients receive vorinostat PO once daily (QD) on days 1-3 in weeks 1-2and undergo fractionated stereotactic body radiation therapy on days 1-5 in weeks 1-2. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days and then every 3 months for 2 years.

Being tested
Vorinostat, Stereotactic Radiosurgery, Laboratory Biomarker Analysis, Pharmacological Study, Therapeutic Conventional Surgery
Medical subject headings
Astrocytoma, Oligodendroglioma, Glioblastoma, Gliosarcoma, Glioma, Brain Neoplasms

What participants receive

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

  • VorinostatDrug

    Also called L-001079038, SAHA, Suberanilohydroxamic Acid, Suberoylanilide Hydroxamic Acid

    Given PO

  • Stereotactic RadiosurgeryRadiation

    Also called SBRT, Stereotactic External Beam Irradiation, Stereotactic Radiation Therapy, Stereotactic Radiotherapy

    Undergo fractionated stereotactic radiation therapy

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Also called pharmacological studies

    Correlative studies

  • Therapeutic Conventional SurgeryProcedure or surgery

    Undergo neurosurgery

Study groups in NCT01378481
Study groupRoleWhat they receive
Treatment (vorinostat, surgery, FSRT)ExperimentalPatients receive high-dose vorinostat PO at 48, 27, and 3 hours prior to surgery. Beginning 2-6 weeks later, patients receive vorinostat PO QD on days 1-3 in weeks 1-2and undergo fractionated stereotactic body radiation therapy on days 1-5 in weeks 1-2. Treatment continues in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Vorinostat; Radiation: Stereotactic Radiosurgery; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Procedure: Therapeutic Conventional Surgery

What is being measured

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

  1. Maximal tolerated dose (MTD), defined as one level below at which 2 of 6 patients experience a dose-limiting toxicity (DLT)

    Analysis of study data will be descriptive, including summary tables of toxicity. An exploratory retrospective trend analysis will be performed assessing for a correlation between plasma drug level and toxicity, using exact logistic regression models.

    Measured: 48 hours

  2. Dose limiting toxicities (grade 3 or higher) defined by Common Toxicity Criteria (CTC) version 4.0

    Analysis of study data will be descriptive, including summary tables of toxicity. An exploratory retrospective trend analysis will be performed assessing for a correlation between plasma drug level and toxicity, using exact logistic regression models.

    Measured: 48 hours

  3. Overall survival (OS)

    Analysis of study data will be descriptive, including Kaplan-Meier estimates of survival outcomes.

    Measured: Up to 2 years

  4. Progression free survival (PFS)

    Analysis of study data will be descriptive, including Kaplan-Meier estimates of survival outcomes.

    Measured: Time from start of treatment to time to progression, up to 2 years

  5. Response rate defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria

    Analysis of study data will be descriptive. A 2-sided exact 95% confidence interval of response rate will be computed.

    Measured: Up to 2 years

Timeline

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

  1. First posted22 Jun 2011 (estimated)
  2. Study startJun 2012
  3. Primary completionAug 2013
  4. Study completionAug 2013

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01378481
Sponsor's protocol ID
NCI-2012-01139
Other IDs
NCI-2012-01139, 11D.101, 9018, P30CA056036
Status last verified
Mar 2014
First submitted
16 Jun 2011
Last updated
23 Dec 2014
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Vorinostat, Stereotactic Radiosurgery and Laboratory Biomarker Analysis in people with Adult Anaplastic Astrocytoma and Adult Anaplastic Oligodendroglioma, 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.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 12 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: stopped early, as of the sponsor's last update on 23 Dec 2014. 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 was stopped early. Results are not available in the source record.

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?

Maximal tolerated dose (MTD), defined as one level below at which 2 of 6 patients experience a dose-limiting toxicity (DLT) (time frame: 48 hours). The study lists 5 primary outcomes in all. 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 NCT01378481.

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 23 Dec 2014.

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