A Phase II Study of Dacomitinib in Progressive Brain Metastases

NCT02047747

Last updated date
Study Location
UCSD Moores Cancer Center
La Jolla, California, 92093-0698, United States
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Brain Cancer
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- 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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- 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.

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Brain CancerA Phase II Study of Dacomitinib in Progressive Brain Metastases
NCT02047747
  1. La Jolla, California
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE A Phase II Study of Dacomitinib in Progressive Brain Metastases
Official Title  ICMJE 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
Brief Summary 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Brain Cancer
Intervention  ICMJE Drug: Dacomitinib
Dacomitinib 45 mg will be administered orally daily. Treatment cycles will consist of 28 days.
Study Arms  ICMJE Experimental: dacomitinib
Dacomitinib 45 mg will be administered orally daily. Treatment cycles will consist of 28 days.
Intervention: Drug: Dacomitinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: June 27, 2016)
4
Original Estimated Enrollment  ICMJE
 (submitted: January 24, 2014)
29
Actual Study Completion Date  ICMJE February 2016
Actual Primary Completion Date February 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02047747
Other Study ID Numbers  ICMJE 130418
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party David Piccioni, M.D., Ph.D, University of California, San Diego
Study Sponsor  ICMJE David Piccioni, M.D., Ph.D
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator:David Piccioni, M.D., Ph.D.University of California Medical Center
PRS Account University of California, San Diego
Verification Date August 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP