Clinical Trials /

A Phase II Study of Dacomitinib in Progressive Brain Metastases

NCT02047747

Description:

The purpose of this study is to determine the disease response, survival, and side effects of an experimental drug called dacomitinib in progressive brain metastases.

Related Conditions:
  • Breast Carcinoma
  • Gastric Carcinoma
  • Lung Carcinoma
  • Melanoma
Recruiting Status:

Terminated

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Phase II Study of Dacomitinib in Progressive Brain Metastases
  • Official Title: A Phase II Study to Evaluate the Efficacy, Safety, and Central Nervous System (CNS) Pharmacokinetics of the HER Family Inhibitor Dacomitinib in Progressive Brain Metastases

Clinical Trial IDs

  • ORG STUDY ID: 130418
  • NCT ID: NCT02047747

Conditions

  • Brain Cancer

Interventions

DrugSynonymsArms
Dacomitinibdacomitinib

Purpose

The purpose of this study is to determine the disease response, survival, and side effects of an experimental drug called dacomitinib in progressive brain metastases.

Detailed Description

      The purpose of this study is to investigate the use of the irreversible pan-ErB kinase
      inhibitor dacomitinib in the treatment of brain metastases, as measured by radiographic
      objective response rate.

      The rationale of this study is three-fold. First, the use of dacomitinib, an irreversible
      pan-ErB kinase inhibitor, is to improve the duration of response seen by reversible, EGFR
      only inhibitors. Inhibition of the multiple ErB kinases may interfere with receptor
      cross-talk as a method of developing resistance; indeed, patients who have failed erlotinib
      treatment for systemic disease have seen responses to dacomitinib. The second rationale is to
      evaluate the pharmacokinetics of the penetration of dacomitinib into the CSF to determine if
      adequate drug levels reach the CNS, and determine if the current dosing regimen is
      appropriate. The third rationale is to determine if specific molecular phenotypes
      preferentially respond to dacomitinib. As part of this study, serum and cerebrospinal fluid
      will be collected and analyzed both for drug levels and for molecular markers to key elements
      of the ErB signaling cascade. The objective of the marker analysis to identify a distinct
      molecular phenotype that may preferentially respond to targeted drug therapy in the future.
    

Trial Arms

NameTypeDescriptionInterventions
dacomitinibExperimentalDacomitinib 45 mg will be administered orally daily. Treatment cycles will consist of 28 days.
  • Dacomitinib

Eligibility Criteria

        Inclusion Criteria:

          -  Pathologically (histologically or cytologically) documented extracranial diagnosis of
             primary lung cancer, melanoma, human epidermal growth factor receptor 2
             (HER2)-amplified breast cancer, or HER2-amplified gastric cancer, with brain
             metastasis detected by contrast enhanced MRI or CT is required. Patients with
             concurrent leptomeningeal diseases are eligible.

          -  Has progression and measureable brain disease in the brain by magnetic resonance
             imaging (MRI) or computed tomography (CT).

          -  Has stable, or no evidence of, extracranial disease and not receiving systemic therapy
             for extracranial disease.

        Note: Patients with stable disease must have already received standard therapy or are
        intolerant to standard therapy.

          -  Prior therapy for brain metastasis is not required; patients may either have refused
             radiation therapy or have received prior radiation therapy. Patients having received
             prior standard whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS)
             must have completed treatment greater than 4 weeks prior to study initiation.

          -  Has recovered from the toxic effects of prior therapy to Common Toxicity Criteria for
             Adverse Effects (CTCAE) Grade 1 or to their clinical baseline.

          -  Age ≥18.

          -  Life expectancy > 3 months in the opinion of the investigator.

          -  KPS ≥ 60%.

          -  Adequate organ and marrow function.

        Exclusion Criteria:

          -  Current or planned use of systemic therapy for extracranial primary tumor.

          -  Current or anticipated use of other investigational agents.

          -  Presence of uncontrolled seizures ≤ 5 days prior first drug dose, defined as status
             epilepticus or multiple seizures not responding to appropriate therapy.

          -  Current or anticipated use of enzyme-inducing anti-epileptic drugs

          -  Insufficient time for recovery from prior therapy: less than 28 days from WBRT or SRS;
             less than 28 days from any investigational agent; less than 28 days from prior
             cytotoxic therapy (except 23 days from prior temozolomide, 14 days from vincristine,
             42 days from nitrosoureas, 21 days from procarbazine administration), and less than 7
             days for non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic
             acid, etc. When radiation necrosis is suspected, confirmatory imaging will be
             performed, and patients with findings consistent with radiation necrosis will be
             excluded.

          -  Current use or anticipated need for treatment with Coumadin® or other agents
             containing warfarin (except low dose Coumadin (1 mg or less daily) administered
             prophylactically for maintenance of in-dwelling lines or ports). Heparin, low
             molecular weight heparin (LWMH), direct thrombin inhibitors and factor Xa inhibitors
             are allowed. Rivaroxaban should be used with caution. Antiplatelet agents are allowed.

          -  Current or anticipated need for treatment with drugs that are known substrates of
             CYP2D6

          -  Current or anticipated need for treatment with proton pump inhibitors. Patients on
             proton pump inhibitors who can be switched to H2-blockers before the start of the
             study are still eligible.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to dacomitinib.

          -  Known severe and/or uncontrolled medical disorder that would impair ability to receive
             study treatment (i.e., uncontrolled diabetes, chronic renal disease, chronic pulmonary
             disease, HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), or active infection).

          -  Impaired cardiac function including any of the following: Congenital long QT syndrome
             or a known family history of long QT syndrome; corrected QT interval (QTc) > 450 msec;
             history or presence of clinically significant ventricular or atrial tachyarrhythmias;
             clinically significant resting bradycardia (< 50 beats per minute); myocardial
             infarction within 1 year of starting study drug; other clinically significant heart
             disease (e.g., unstable angina, congestive heart failure, or uncontrolled
             hypertension)

          -  Pregnant or nursing. There is a potential for congenital abnormalities and for this
             regimen to harm nursing infants.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Intra-cranial Objective Response Rate
Time Frame:2 months
Safety Issue:
Description:Intra-cranial objective response rate at 2 months as assessed by the Response Assessment in Neuro-oncology (RANO) criteria

Secondary Outcome Measures

Measure:Treatment-emergent Adverse Events
Time Frame:End of Treatment (4-6 weeks after permanent discontinuation of study treatment for any reason)
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:David Piccioni, M.D., Ph.D

Trial Keywords

  • Brain
  • Metastasis
  • human epidermal receptor (HER)

Last Updated

August 8, 2016