Brain CancerPhase 2NCT02047747
A Phase II Study of Dacomitinib in Progressive Brain Metastases
A Phase 2 study testing Dacomitinib in people with Brain Cancer, run by David Piccioni, M.D., Ph.D at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Cancer
- What is being tested?
- Dacomitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2014to Feb 2016
- Phase
- Phase 2
- 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
- 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.
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- Age ≥18.
- Life expectancy > 3 months in the opinion of the investigator.
- KPS ≥ 60%.
- Adequate organ and marrow function.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
UCSD Moores Cancer Center
La Jolla, California, 92093-0698
About this study
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
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.
Read the 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.
- Conditions
- Brain Cancer
- Being tested
- Dacomitinib
- Keywords
- Brain, Metastasis, human epidermal receptor (HER)
- Medical subject headings
- Brain Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DacomitinibDrug
Dacomitinib 45 mg will be administered orally daily. Treatment cycles will consist of 28 days.
| Study group | Role | What they receive |
|---|---|---|
| dacomitinib | Experimental | Dacomitinib 45 mg will be administered orally daily. Treatment cycles will consist of 28 days. Receives: Drug: Dacomitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intra-cranial Objective Response Rate
Intra-cranial objective response rate at 2 months as assessed by the Response Assessment in Neuro-oncology (RANO) criteria
Measured: 2 months
Secondary outcomes (1)
Treatment-emergent Adverse Events
Measured: End of Treatment (4-6 weeks after permanent discontinuation of study treatment for any reason)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2014 (estimated)
- Study startFeb 2014
- Primary completionFeb 2016
- Study completionFeb 2016
Why it stopped: slow enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Brain CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- David Piccioni, M.D., Ph.D
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Sponsor-investigator, David Piccioni, M.D., Ph.D, University of California, San Diego
- Investigators
- David Piccioni, M.D., Ph.D., Principal investigator, University of California Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02047747
- Sponsor's protocol ID
- 130418
- Status last verified
- Aug 2016
- First submitted
- 15 Jan 2014
- Last updated
- 22 Sep 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02047747
- Acronym / sponsor ID
- 130418
- Conditions
- Brain Cancer
- Keywords
- Brain, Metastasis, human epidermal receptor (HER)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: slow enrollment
- Enrolment
- 4 participants (actual)
- Lead sponsor
- David Piccioni, M.D., Ph.DUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- Feb 2014
- Primary completion
- Feb 2016 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 28 Jan 2014 (estimated)
- Results
- Posted 9 Aug 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| dacomitinib | Experimental | Drug: DacomitinibDacomitinib 45 mg will be administered orally daily. Treatment cycles will consist of 28 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DacomitinibDacomitinib 45 mg will be administered orally daily. Treatment cycles will consist of 28 days. | Drug | dacomitinib |
Primary outcome
Intra-cranial Objective Response Rate
Time frame: 2 months
Intra-cranial objective response rate at 2 months as assessed by the Response Assessment in Neuro-oncology (RANO) criteria
1 secondary outcome
Treatment-emergent Adverse Events
Time frame: End of Treatment (4-6 weeks after permanent discontinuation of study treatment for any reason)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Piccioni, M.D., Ph.D. principal investigator
University of California Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dacomitinib in people with Brain Cancer, run by David Piccioni, M.D., Ph.D at 1 site 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 10 inclusion and 12 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: stopped early, as of the sponsor's last update on 22 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 9 Aug 2016). 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?
Intra-cranial Objective Response Rate (time frame: 2 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 22 Sep 2016.