ClinicalTrials.gov
ClinicalTrials.gov Menu

Vorinostat and Concurrent Whole Brain Radiotherapy for Brain Metastasis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01600742
Recruitment Status : Terminated (Sponsor stops to provide the study drug.)
First Posted : May 17, 2012
Last Update Posted : January 9, 2014
Sponsor:
Information provided by (Responsible Party):
National Taiwan University Hospital

Brief Summary:
Vorinostat is a potent and well tolerated HDAC inhibitor. It has been reported to enhance radiosensitivity of cancer cells. We hypothesize that the addition of vorinostat to WBRT may increase therapeutic efficacy for patients with brain metastases.

Condition or disease Intervention/treatment Phase
Brain Metastasis Drug: Vorinostat Drug: Placebo Phase 2

Detailed Description:

Whole brain radiotherapy (WBRT) is the treatment of choice for the majority of patients with brain metastases. Although WBRT yields high radiologic response rate (27~56%) and is effective in palliation of neurologic symptoms, the response duration is limited and neurologic progression remains the main cause of death in a significant number of patients.

Vorinostat is reasonably well tolerated and there is also compelling evidence that vorinostat may serve as a radiosensitizer. Preclinical studies of HDAC inhibition have also shown efficacy in neuron protection. These data suggest that the addition of vorinostat to the standard therapy of WBRT may potentially increase their therapeutic efficacy without increasing neurotoxicity, and support the rationale of this phase II trial of vorinostat with WBRT in patients with brain metastases.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Vorinostat and Concomitant Whole Brain Radiation Therapy in Patients With Brain Metastases: A Randomized, Double-blind, Placebo-controlled, Phase II Study
Study Start Date : August 2012
Actual Primary Completion Date : December 2013
Actual Study Completion Date : December 2013

Resource links provided by the National Library of Medicine

Drug Information available for: Vorinostat

Arm Intervention/treatment
Active Comparator: WBRT, placebo Drug: Placebo

Randomization phase:

WBRT: 2.5 Gy per fraction per day, day 1 through day 5 every week for 15 days, to a total dose of 37.5Gy.

Vorinostat or placebo: 400 or 300 mg/day during radiation therapy (based on the results of run-in phase), day 1 through day 7 every week till one day after WBRT.


Experimental: WBRT and concurrent vorinostat Drug: Vorinostat

Run-in phase:

WBRT: 2.5 Gy per fraction per day, day 1 through day 5 every week for 15 days, to a total dose of 37.5Gy.

Vorinostat: 400 mg/day during WBRT, day 1 through day 7 every week till one day after WBRT.

Randomization phase:

WBRT: 2.5 Gy per fraction per day, day 1 through day 5 every week for 15 days, to a total dose of 37.5Gy.

Vorinostat or placebo: 400 or 300 mg/day during radiation therapy (based on the results of run-in phase), day 1 through day 7 every week till one day after WBRT.





Primary Outcome Measures :
  1. To evaluate brain-specific progression free survival rate at 6 months [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. brain-specific PFS [ Time Frame: from randomization to progression of brain metastasis or death, assessed up to 36 months ]
  2. PFS [ Time Frame: from randomization to progression or death, assessed up to 36 months ]
  3. response rate [ Time Frame: 6 months ]
  4. time to neuro-cognitive progression [ Time Frame: 12 months ]
  5. time to neurologic progression [ Time Frame: 12 months ]
  6. HRQoL [ Time Frame: 12 months ]
  7. Overall survival [ Time Frame: from randomization to death, assessed up to 36 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with a histologic diagnosis of a malignancy (lung and breast cancers) and radiologic evidence of brain metastases that are not suitable for surgery or radiosurgery as judged on the basis of the lesion size, number, location and the patients' personal choices.
  • Patients with controlled systemic disease for >6 weeks (as judged on a case by case situation)
  • Age≧20 years
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≦3
  • Life expectancy of ≧6 months
  • No prior cranial radiotherapy
  • Negative urine pregnancy test done ≤7 days prior to registration, for women of childbearing potential only.
  • Measurable lesions by gadolinium-enhanced MRI or contrast-enhanced CT scans. (≧10mm on T1-weighted gadolinium enhanced MRI or contrast-enhanced CT)
  • Patients must have adequate organ and marrow reserve measured within 7 days prior to randomization as defined below:

    1. Hemoglobin >8.0 gm/dL;
    2. Absolute neutrophil count > 1,000/mcL;
    3. Platelets >100,000/mcL;
    4. Total bilirubin ≤ 1.5 x UNL (upper normal limit);
    5. AST(SGOT)/ALT(SGPT) ≤ 2.5 x UNL; for patients with liver metastases, AST(SGOT)/ALT(SGPT) ≤ 5 x UNL is allowed;
    6. Serum creatinine ≤ 1.5 x UNL;
    7. PTT ≤ UNL;
    8. INR ≤ 1.5;
    9. Serum sodium, calcium, potassium, and magnesium levels are within normal limits.
  • Patients (or a surrogate) must be able to comply with study procedures and sign informed consent.

Exclusion Criteria:

  • Prior cranial RT.
  • Known hypersensitivity to any of the components of vorinostat.
  • Use of Valproic acid or other histone deacetylase inhibitor, ≤2 weeks prior to registration and during treatment.
  • Uncontrolled infection.
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and adverse events of the prescribed regimens or limit compliance with study requirements.
  • History of myocardial infarction or unstable angina ≤6 months prior to registration or congestive heart failure (CHF) requiring use of ongoing maintenance therapy, or life-threatening ventricular arrhythmias.
  • Inability to take oral medications.
  • Receiving any other investigational agent.
  • Congenital long QT syndrome.
  • Prolonged QTc interval (>450 msec)
  • Any of the following Category I drugs that are generally known to have a risk of causing Torsades de Pointes ≤7 days prior to registration: Quinidine, procainamide, disopyramide, amiodarone, sotalol, ibutilide, dofetilide, erythromycin, clarithromycin, chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide, cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine
  • Any of the following:

    1. Pregnant women
    2. Nursing women
    3. Men or women of childbearing potential who are unwilling to employ adequate contraception throughout the duration of the study and for 3 weeks after treatment has ended.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01600742


Locations
Taiwan
National Taiwan University Hospital
Taipei, Taiwan, 100
Sponsors and Collaborators
National Taiwan University Hospital
Investigators
Principal Investigator: Pei-Fang Wu, MD National Taiwan University Hospital

Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT01600742     History of Changes
Other Study ID Numbers: 201110052MB
First Posted: May 17, 2012    Key Record Dates
Last Update Posted: January 9, 2014
Last Verified: January 2014

Additional relevant MeSH terms:
Neoplasm Metastasis
Brain Neoplasms
Neoplastic Processes
Neoplasms
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vorinostat
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action