Vorinostat and Concurrent Whole Brain Radiotherapy for Brain Metastasis

NCT01600742 | Terminated Phase 2 DMC

• 1 other identifier: 201110052MB
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Brain Metastasis

Outcome Measures

Primary Outcomes (1)

• To evaluate brain-specific progression free survival rate at 6 months

  6 months

Secondary Outcomes (7)

• brain-specific PFS

  from randomization to progression of brain metastasis or death, assessed up to 36 months

• PFS

  from randomization to progression or death, assessed up to 36 months

• response rate

  6 months

• time to neuro-cognitive progression

  12 months

• time to neurologic progression

  12 months

Study Arms (2)

WBRT, placebo

ACTIVE COMPARATOR

Drug: Placebo

WBRT and concurrent vorinostat

EXPERIMENTAL

Drug: Vorinostat

Interventions

Vorinostat DRUG

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.

WBRT and concurrent vorinostat

Placebo DRUG

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.

WBRT, placebo

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Hemoglobin \>8.0 gm/dL;
• Absolute neutrophil count \> 1,000/mcL;
• Platelets \>100,000/mcL;
• Total bilirubin ≤ 1.5 x UNL (upper normal limit);
• AST(SGOT)/ALT(SGPT) ≤ 2.5 x UNL; for patients with liver metastases, AST(SGOT)/ALT(SGPT) ≤ 5 x UNL is allowed;
• Serum creatinine ≤ 1.5 x UNL;

You may not qualify if:

• 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:
• Pregnant women
• Nursing women
• 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.

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (1)

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

MeSH Terms

Conditions

Brain Neoplasms

Interventions

Vorinostat

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Study Officials

• Pei-Fang Wu, MD

  National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2012
• First Posted: May 17, 2012
• Study Start: August 1, 2012
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: January 9, 2014

Record last verified: 2014-01

Locations

TW (1)