Current or prior known meningeal metastases Known brain metastases that are symptomatic or untreated Note: Patients with known brain metastases who are asymptomatic and have had post-treatment imaging that indicates stable brain disease are eligible. Note that brain imaging in patients with known brain metastases is required within 8 weeks prior to initiation of study therapy.
* Any investigational agent within 4 weeks prior to initiating study treatment
* Previous therapy with neratinib
* Active uncontrolled diarrhea leading to dehydration or electrolyte disturbances not easily controlled with oral repletion
* Inability to swallow medication
* Known or suspected malabsorption condition or obstruction. Note: Use of pancreatic enzyme supplements is allowed to control malabsorption
* Inability to shift medications as follows: Antacids (eg, calcium carbonate): dose at least 3 hours after dosing with neratinib. H2 receptor antagonists: dose must be taken at least 2 hours after or 10 hours before dosing with neratinib
* Resting systolic blood pressure (BP) < 100 mmHg
* Active or clinically significant cardiac disease including any of the following:
* Unstable angina (eg, anginal symptoms at rest) or onset of angina within 3 months prior to initiating study treatment
* Myocardial infarction diagnosed within 6 months prior to initiating study treatment
* Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers
* New York Heart Association (NYHA) class III or IV congestive heart failure
* Seizure disorder requiring an enzyme inducing antiepileptic medication (EIAED)
* Serious (ie, ≥ grade 3) uncontrolled infection
* Chronic or active hepatitis B or C infection with elevated transaminase levels
* Pleural effusion or ascites that causes respiratory compromise (ie, ≥ grade 2 dyspnea)
* Known mitochondrial disorder caused by mutations in mitochondrial DNA polymerase gamma (γ)
* Known urea cycle disorders
* Planned ongoing treatment with other drugs thought to potentially have adverse interactions with either of the medications included in the study treatment:
* Proton pump inhibitors (PPIs)
* High-risk P-glycoprotein (P-gp) substrates (eg, digoxin, dabigatran, fexofenadine). Other anticoagulants are not considered high-risk P-gp substrates
* Strong or moderate CYP3A4 inhibitors and/or Strong or moderate CYP3A4 inducers. Examples of clinical inhibitors and clinical inducers for P450-mediated metabolism and classification of strong, moderate, and weak interactions are available through the FDA website, Tables 3-2 and 3-3: http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm Note: If such medications have been used, patients must have discontinued these agents ≥ 2 weeks prior to initiating study treatment
* Pregnancy or breastfeeding
* Medical, psychological, or social condition that, in the opinion of the investigator, may increase the patient's risk or limit the patient's adherence with study requirements