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Brain MetastasesPhase 1NCT00838929

Study of the Combination of Vorinostat and Radiation Therapy for the Treatment of Patients With Brain Metastases

A Phase 1 study testing Vorinostat and Radiation Therapy in people with Brain Metastases, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 2 sites in United States.

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

Vorinostat in combination with radiation therapy can be administered safely and will be tolerated in patients with brain metastases, while providing an assessment of the anti-tumor activity of this combination. This is a multi-center, open-label, non-randomized Phase I study in patients with brain metastases. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Brain Metastases
What is being tested?
Vorinostat and Radiation Therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
2 sitesUnited States
Study dates
Mar 2009to Mar 2015
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 requiring a 3 week course of fractionated whole brain radiation therapy for brain metastases.
  • Age > or = 18
  • Histological or cytological diagnosis of a malignancy.
  • Patients who have only 1-3 metastases are frequently treated with stereotactic radiation. Nonetheless, if the treating physician decides that whole brain radiotherapy is the appropriate treatment such patients would be eligible to enroll upon in the study.
  • Radiographic evidence of brain metastasis.
  • Measurable disease preferred but not required for eligibility
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  • Patient must have performance status of < or = 2 on the ECOG Performance Scale.
  • Life expectancy of > or = 3 months
  • Resolution of all acute toxic effects of prior chemotherapy or radiotherapy or surgical procedures to NCI CTCAE Version 3.0 grade < or = 1.
  • Adequate organ function as defined by the following criteria:
  • Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) < or = 2.5 x local laboratory upper limit of normal (ULN), or AST and ALT < or = 5 x ULN if liver function abnormalities are due to underlying malignancy
  • Total serum bilirubin < or = 1.5 x ULN
  • Absolute neutrophil count (ANC) > or = 1500/µL
  • Platelets > or = 100,000/µL
  • Hemoglobin > or = 9.0 g/dL
  • Serum calcium < or = 12.0 mg/dL
  • Serum creatinine < or = 1.5 x ULN
  • Potassium level within normal limits.
  • Magnesium level within normal limits.
  • Female patient of childbearing potential has a negative serum pregnancy test β-hCG within 72 hours prior to receiving the first dose of Vorinostat .
  • Female patient is either post menopausal, free from menses for > or = 2 years, surgically sterilized, or willing to use 2 adequate barrier methods of contraception to prevent pregnancy, starting with Visit 1.
  • Male patient agrees to use an adequate method of contraception for the duration of the study.
  • Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures.
  • INR < 1.5 or a PT/PTT within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR should be measured prior to initiation of Vorinostat and monitored at least weekly, or as defined by the local standard of care, until INR is stable.
  • Patient is available for study related assessments, and management at the treating institution, for the duration of the study.

Who cannot join

  • Previous cranial irradiation (whether whole or partial brain, single fraction or multiple fractions) within the previous six months.
  • Patient who has had chemotherapy within 21 days, non-cranial radiotherapy within 10 days, or who has not recovered from adverse events due to agents administered more than 30 days earlier.
  • Patient is currently participating or has participated in a study with an investigational compound or device within 14 days of initial dosing with study drug(s).
  • Patient has had prior treatment with an HDAC inhibitor (e.g., romidepsin (Depsipeptide), NSC-630176, MS 275, LAQ-824, belinostat (PXD-101), LBH589, MGCD0103, CRA024781, etc). Patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid, as anti-tumor therapy should not enroll in this study. Patients who have received such compounds for other indications, e.g. valproic acid for epilepsy, may enroll after a 30-day washout period under neurological supervision.
  • Patients with markedly elevated intracranial pressure.
  • Cardiac disease: Congestive heart failure > class II NYHA. Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
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  • Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
  • An extended QTc interval on baseline EKG examination. Normal values: male < 430ms, female <450 ms.
  • Concomitant use of medications known to extend the QTc interval: Quinidine, Procainamide, Disopyramide, Dofetilide, Ibutilide, Sotalol, Amiodarone, Bepridil, Cisapride, Macrolides, Erythromycin, Clarithromycin, Fluoroquinolones, Sparfloxacin, Antiprotozoals, Pentamidine, Antimalarials, Halofantrine, Chloroquine, Phenothiazine neuroleptics, Thioridazine, Chlorpromazine, Mesoridazine, Butyrophenone neuroleptics, Droperidol, Haloperidol, Diphenylpiperidine neuroleptics, Pimozide, Arsenic trioxide, Methadone, Cesium, Licorice, Zhigancao
  • Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.
  • Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
  • Active clinically serious infection > CTCAE Grade 2
  • NCI CTCAE grade 3 hemorrhage within 4 weeks of starting the study treatment.
  • Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
  • Pulmonary hemorrhage/bleeding event > or = CTCAE Grade 2 within 4 weeks of first dose of study drug.
  • Serious non-healing wound, ulcer, or bone fracture.
  • Evidence or history of bleeding diathesis or coagulopathy
  • Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.
  • Use of St. John's Wort or rifampin (rifampicin).
  • Any condition that impairs patient's ability to swallow whole pills.
  • Any malabsorption problem.
  • Pregnancy or breastfeeding. Female subjects must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy. All female subjects with reproductive potential must have a negative pregnancy test (serum or urine) prior to enrollment. Male subjects must be surgically sterile or must agree to use effective contraception during the period of therapy. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate.
  • Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study.
  • Documented history of cranial hemorrhage
  • Patient has an active infection or has received intravenous antibiotics, antiviral, or antifungal agents within 2 weeks prior to the start of the study drug.
  • Patient has uncontrolled inter-current illness or circumstances that could limit compliance with the study, including, but not limited to the following: active infection, acute or chronic graft versus host disease, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric conditions.
  • Patient has a history or current evidence of any condition, therapy, or lab abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study or is not in the best interest of the patient to participate.
  • Patient has a history of a gastrointestinal surgery or other procedures that might, in the opinion of the investigator, interfere with the absorption or swallowing of the study drugs.
  • Patient has known hypersensitivity to the components of study drug or its analogs.
  • Patient has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Patient is, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs, substance abuse or had a recent history (within the last year) of drug or alcohol abuse.
  • Patient is pregnant or breast feeding, or expecting to conceive or father children within the projected duration of the study.

Trial locations and contacts

2 sites in 1 country.

United States2 sites
  • The University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

Other trials in United States

About this study

Official title: Phase I Study of the Combination of Vorinostat and Radiation Therapy for the Treatment of Patients With Brain Metastases

Vorinostat in combination with radiation therapy can be administered safely and will be tolerated in patients with brain metastases, while providing an assessment of the anti-tumor activity of this combination.

This is a multi-center, open-label, non-randomized Phase I study in patients with brain metastases. Patients will be administered oral Vorinostat and radiation therapy and will be treated for 3 weeks. Patients will be enrolled in cohorts and will be treated at sequentially rising dose levels of Vorinostat combined with radiation therapy. We will initially enter 3 subjects at each dose. If none of the three experiences a dose-limiting toxicity we will proceed to the next dose. If one of the three experiences that level of toxicity, we will accrue 3 more subjects at that dose. If at any time there are two or more dose-limiting toxicities (in the 3-6 subjects) on a given dose, we will drop down to a lower dose. Dose escalation will continue until the MTD of Vorinostat and radiation therapy is established. The MTD will then be one dose below the DLT occurring in at least 1 out of 3 subjects (2 out of 6 patients).

Read the detailed description

In recent years, a number of investigators have shown that combining signal transduction agents with ionizing radiation results in significant antitumor effects without an increase in normal tissue toxicity. There are numerous lines of evidence that Histone deacetylase (HDAC) inhibitors have been shown to enhance the radiosensitivity of tumor cells in vitro and in vivo 1-6. Vorinostat (Zolinza, suberoylanilide hydroxamic acid - SAHA) a potent histone deacetylase, has recently been approved for clinical use for cutaneous T-cell lymphoma. It has the potential to inhibit tumor growth and proliferation7-13, tumor angiogenesis14 and enhance radiation response15 with minimal toxicity. This phase I study, is based on the range of efficacy of Vorinostat and its ability to cross the blood-brain barrier. This study will evaluate the safety of combination of Vorinostat and daily-fractionated radiation therapy. This information is critical for any combined future combined modality trials that involves radiation therapy to the brain.

Vorinostat was approved by the US Food and Drug Administration (FDA) on 6-Oct-2006 for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma (CTCL) who have progressive, persistent or recurrent disease on or following two systemic therapies.

Based on preclinical, clinical efficacy and safety data, it is anticipated that Vorinostat in combination with radiation therapy can be administered safely and will be tolerated in patients with brain metastases. In addition, within the recognized limits of a Phase I clinical trial, this study may provide an assessment of the anti-tumor activity of Vorinostat in combination with radiation therapy in patients with brain metastases.

The present study will investigate the safety, tolerability and spectrum of side effects of Vorinostat in combination with radiation therapy. As such, this study will characterize the dose limiting toxicities (DLT) and maximum tolerated dose (MTD) of in combination with radiation therapy in patients with brain metastases.

Being tested
Vorinostat, Radiation Therapy
Keywords
brain metastases, radiation, vorinostat, lung cancer, breast cancer
Medical subject headings
Brain Neoplasms, Lung Neoplasms, Breast Neoplasms

What participants receive

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

  • VorinostatDrug

    Also called Zolinza

    All doses given for 3 weeks

    Dose level -2 - 50 mg PO qd (to be used in de-escalation if toxicity occurs) Dose level -1 - 100 mg PO qd (to be used in de-escalation if toxicity occurs) Dose level I - 200 mg PO qd (initial starting dose) Dose level II - 300 mg PO qd Dose level III - 400 mg PO qd

  • Radiation TherapyRadiation

    Also called Radiation oncology, Radiotherapy, XRT

    Patients will take Vorinostat daily during radiation therapy, they will be recommended to swallow the capsule 60-90 minutes prior to estimate time of radiation.

Study groups in NCT00838929
Study groupRoleWhat they receive
Vorinostat (200 mg) and radiationExperimentalCohort 1: Patients receive 200 mg of Vorinostat and radiation
Receives: Drug: Vorinostat; Radiation: Radiation Therapy
Vorinostat (300 mg) and radiationExperimentalCohort 2: Patients receive 300 mg of vorinostat and radiation
Receives: Drug: Vorinostat; Radiation: Radiation Therapy
Vorinostat (400 mg) and radiationExperimentalCohort 3: Patients receive 400 mg of vorinostat and radiation
Receives: Drug: Vorinostat; Radiation: Radiation Therapy

What is being measured

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

  1. Maximum Tolerated Dose (MTD) and Recommended Phase II Dose (RP2D) of Vorinostat and Radiotherapy in Patients With Brain Metastases.

    To determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of Vorinostat and radiotherapy in patients with brain metastases.

    The maximum tolerated dose (MTD) will be one dose below the DLT occurring in at least 1 out of 3 subjects.

    Dose level -2: 50 mg PO qd (to be used in de-escalation if toxicity occurs) Dose level -1: 100 mg PO qd (to be used in de-escalation if toxicity occurs) Dose level I: 200 mg PO qd (initial starting dose) Dose level II: 300 mg PO qd Dose level III: 400 mg PO qd

    Measured: Weekly during treatment On Last day of treatment (30 days after last drug dose) Follow-up (every 3 months)

Timeline

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

  1. First posted9 Feb 2009 (estimated)
  2. Study startMar 2009
  3. Primary completionJan 2012
  4. Study completionMar 2015

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
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00838929
Sponsor's protocol ID
08D.522
Other IDs
2008-19, JT 1331
Status last verified
May 2025
First submitted
6 Feb 2009
Last updated
4 May 2025
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Vorinostat and Radiation Therapy in people with Brain Metastases, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 2 sites 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 25 inclusion and 32 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 4 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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?

Yes. Results are posted in the registry (first posted 1 Nov 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Maximum Tolerated Dose (MTD) and Recommended Phase II Dose (RP2D) of Vorinostat and Radiotherapy in Patients With Brain Metastases. (time frame: Weekly during treatment On Last day of treatment (30 days after last drug dose) Follow-up (every 3 months)). 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 4 May 2025.

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