Dacomitinib in Treating Patients with Progressive Brain Metastases

Inclusion Criteria

• Ability to understand and the willingness to provide informed consent
• Pathologic (histologically or cytologically) documented extracranial diagnosis of primary lung cancer, melanoma, human epidermal growth factor receptor 2 (HER2)-amplified or immuno-positive breast cancer, or HER2-amplified or immuno-positive gastric cancer, with brain metastasis detected by contrast enhanced magnetic resonance imaging (MRI) or computed tomography (CT) is required; patients with concurrent leptomeningeal diseases are eligible
• Has progression and measurable 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 metastases 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; patients are either inappropriate candidates for surgical resection or they may have refused surgical resection
• Has recovered from the toxic effects of prior therapy to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or to their clinical baseline
• Life expectancy > 3 months in the opinion of the investigator
• Karnofsky performance status (KPS) >= 60%
• Neurologically stable defined as receiving no, stable, or tapering doses of corticosteroids for >= 5 days prior to drug dosing; treatment with corticosteroids during the study is allowed, and can be adjusted by the investigator during the study; changes in steroid dose are incorporated into the Revised Assessment in Neuro-Oncology (RANO) imaging criteria
• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
• Platelet count >= 100 x 10^9/L
• Hemoglobin >= 9.0 g/dL
• Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) =< 2.5 x institution’s upper limit of normal (ULN)
• Total bilirubin =< 1.5 x institution’s ULN
• Serum creatinine =< 1.5 x institution’s ULN or 24-hour creatinine clearance >= 50 ml/min
• Alkaline phosphatase (ALP) =< 2.5 x ULN unless considered tumor related
• Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately * A woman of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: ** Has not undergone a hysterectomy or bilateral oophorectomy; or ** Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
• Woman of child-bearing potential has negative pregnancy test before the initiation of study drug dosing

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 (EIAED)
• 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, irinotecan or topotecan administration), and * Less than 7 days for non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. * When radiation necrosis is suspected, standard of care (SOC) confirmatory imaging, such as MRI perfusion, magnetic resonance (MR) spectroscopy and or positron emission tomography (PET) 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 cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6)
• Current or anticipated need for treatment with proton pump inhibitors (PPI); patients on proton pump inhibitors who can be switched to histamine receptor H2 (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, human immunodeficiency virus [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 (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