Hepatic Impairment Study For Crizotinib In Advanced Cancer Patients

Exclusion Criteria

• •Untreated esophageal varices observed on EGD or imaging study; however, patients with known portal hypertension and evidence of varices on EGD or imaging study who have undergone appropriate therapy as indicated within the last 6 months (if applicable) are eligible for enrollment.
• •Uncontrolled ascites that is not stable with medical management (i.e., on diuretics and salt restriction) as defined by requiring therapeutic paracentesis more than once every 4 weeks.
• •Episodes of hepatic encephalopathy within the last 4 weeks. Patients with prior episodes of hepatic encephalopathy who are clinically stable on lactulose, neomycin, and/or xifaxan therapy are allowed.
• •Prior therapy with crizotinib.
• •Spinal cord compression.
• •Carcinomatous meningitis or leptomeningeal disease
• •Any of the following within the 6 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, or cerebrovascular accident including transient ischemic attack.
• •Symptomatic congestive heart failure.
• •Ongoing cardiac dysrhythmias of NCI CTCAE Grade ≥ 2, uncontrolled atrial fibrillation of any grade, or an average of triplicate QTc interval \>470 msec.
• •History of extensive disseminated/bilateral or known presence of interstitial fibrosis or interstitial lung disease, including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, and pulmonary fibrosis, but not history of prior radiation pneumonitis.
• •Active hemolysis or evidence of biliary sepsis.
• •Pregnant females; breastfeeding females; males and females of childbearing potential; males and females of childbearing potential not using highly effective contraception or not agreeing to continue highly effective contraception for at least 28 days after last dose of investigational product; males and females of childbearing potential not using two (2) methods of highly effective contraception or not agreeing to continue two (2) methods of highly effective contraception for at least 28 days after last dose of investigational product.
• •Use of drugs or foods that are known strong CYP3A4 inhibitors, including but not limited to atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole, and grapefruit or grapefruit juice.
• •Use of drugs that are known strong CYP3A4 inducers, including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, and St. John's wort.
• •Use of drugs that are CYP3A4 substrates with narrow therapeutic indices, including but not limited to dihydroergotamine, ergotamine, and pimozide.
• •Other severe acute or chronic medical (may include severe gastrointestinal conditions such as chronic diarrhea or ulcer disease) or psychiatric conditions, or laboratory abnormalities that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of the study results and, in the judgment of the investigator, would make the patient inappropriate for study entry.
• •Patients who had prior major gastrointestinal surgery removing part of gastrointestinal tract and/or gall bladder.