Brigatinib in Treating Patients with ALK and ROS1 Gene Alterations and Locally Advanced or Metastatic Solid Cancers

Inclusion Criteria

• Patients with histologically or cytologically confirmed diagnosis of locally advanced or metastatic solid tumors
• Patients must have activating genomic alterations in ALK or ROS1 (mutations, fusions or amplifications) by any validated Clinical Laboratory Improvement Act (CLIA)-certified molecular testing (fluorescence in situ hybridization [FISH], polymerase chain reaction [PCR] or next-generation sequencing [NGS] data are acceptable); CLIA validated results from other institutions and commercial diagnostic labs (e.g. Foundation Medicine) are also acceptable
• Patients with progressive disease on any previous therapy including crizotinib and other ALK tyrosine kinase inhibitors (TKIs), chemotherapy or immunotherapy
• Patients with locally advanced or metastatic solid tumors who have received no previous therapy of any kind (i.e. first-line therapy) are eligible
• Patients with brain metastases or metastases elsewhere within the central nervous system (CNS) are eligible for study; patients must be neurologically stable and asymptomatic
• Patients with tumor suitable for biopsy (as assessed by trained specialists in interventional radiology) and medically fit to undergo a biopsy or surgical procedure will have mandatory pre-treatment tumor biopsy or sampling; however, if patients do not have a tumor suitable for biopsy but have another tissue (preferably progressive metastatic site) available for molecular evaluation this will be acceptable
• Patients with solid tumors must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1; Note: previously irradiated lesions may not be used for target lesions; unless there is unambiguous radiological progression after radiotherapy; brain lesions may not be used as target lesions if they were: 1) previously treated with whole brain radiation therapy (WBRT) within 3 months, or 2) previously treated by stereotactic radiosurgery (SRS) or surgical resection
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Life expectancy of greater than 3 months
• Patients with multiple malignancies remain eligible
• Patients with an inherited cancer syndrome or a medical/family history suggestive of an inherited cancer syndrome remain eligible
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and through 4 months after the end of treatment; for women of childbearing potential, a negative pregnancy test must be documented prior to registration
• Absolute neutrophil count >= 1,500/mcL
• Hemoglobin >= 10 g/dL
• Platelet count >= 75,000/mcL
• Total bilirubin =< 1.5 x upper limit of normal (ULN), unless due to Gilbert’s syndrome (< 5 if metastatic involvement of the liver)
• Serum lipase =< 1.5 x ULN
• Serum amylase =< 1.5 x ULN
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/ alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN
• Left ventricular ejection fraction (LVEF) >= 50% by echocardiogram or multi-gated acquisition (MUGA)
• Normal QT interval on screening electrocardiogram (ECG), defined as QT interval corrected of =< 450 ms in males or =< 470 ms in females
• Serum creatinine =< 1.5 mg/dL OR calculated creatinine clearance (Cockroft-Gault formula) >= 60 mL/min OR 24-hour urine creatinine clearance >= 60 mL/min
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Patients with hematological malignancies
• Patients with ALK positive (+) lung cancer
• Major surgery (e.g. thoracic, abdominal, vascular, neurosurgery) within 30 days prior to registration on study
• Pregnant women or mothers who are breastfeeding
• Patients who are incarcerated
• Patients who have a history or the presence at baseline of pulmonary interstitial disease or drug-related pneumonitis, or radiation pneumonitis
• Patients who have a known history of human immunodeficiency virus (HIV); testing not required in the absence of history
• Patients with history of clinically significant bleeding disorder or history of active significant gastrointestinal (GI) bleeding within 3 months of first dose of brigatinib
• Patients who have malabsorption syndrome or other GI illness or condition that could affect oral absorption of the study drug
• History of allergic or suspected hypersensitivity reactions attributed to compounds of similar chemical or biologic composition to brigatinib
• Patients with history of clinically significant atrial arrhythmias (requiring any anti-arrhythmic therapy or as determined by the treating physician) or any history of ventricular arrhythmias
• Patients who have significant, uncontrolled or active cardiovascular disease, including but not restricted to the following: * Myocardial infarction (MI) within 6 months prior to first dose of brigatinib * Unstable angina (UA) within 6 months prior to first use * Decompensated congestive heart failure within 6 months prior to first dose * Cerebrovascular accident (CVA) or transient ischemic attack (TIA) within 6 months prior to first dose
• Clinically significant, uncontrolled intercurrent illness including, but not limited to: * Symptomatic or active infection requiring intravenous (IV) antibiotics * Psychiatric illness and/or social situations that would limit compliance with completion of study requirements
• Patients on medications known to be associated with torsades de pointes
• Patients who have uncontrolled hypertension; patients with hypertension should be under treatment on study entry to control blood pressure
• Patients who have received cytotoxic chemotherapy, investigational agents, or radiation within 14 days, except stereotactic radiosurgery (SRS) or stereotactic body radiosurgery
• Patients who have received monoclonal antibodies or had major surgery within 30 days of the first dose of brigatinib
• Patients who have not recovered (=< Common Terminology Criteria for Adverse Events [CTCAE] grade 1) from adverse events (with the exception of alopecia) due to agents administered more than 4 weeks earlier
• Patients with symptomatic CNS metastases that are neurologically unstable or require increasing dose of corticosteroids
• Patients with current spinal cord compression