Pharmacokinetics of Alisertib in Adults With Advanced Solid Tumors or Relapsed/Refractory Lymphoma With Varying Degrees of Hepatic Function

Exclusion Criteria

• •1. Participants of North/East Asian ethnicity (ie, Japanese, Chinese, Korean) will be excluded.
• •2. Recurrent nausea and/or vomiting within 14 days before the first dose of alisertib or known gastrointestinal (GI) abnormality or GI procedure that could interfere with or modify the oral absorption or tolerance of alisertib. Examples include, but are not limited to, disease-related bowel obstruction, pancreatic insufficiency, use of pancreatic enzymes, a gastric condition (such as severe reflux or active peptic ulcer disease) that requires chronic and uninterrupted use of proton pump inhibitors, partial gastrectomy, history of small intestine surgery, and celiac disease.
• •3. Participants requiring treatment with clinically significant enzyme inducers, such as the enzyme-inducing anti-epileptic drugs phenytoin, carbamazepine, phenobarbital, oxcarbazepine, primidone, rifampin, rifabutin, rifapentine, or St. John's wort within 14 days before the first dose of alisertib or requiring the use of these medications during the study.
• •4. A medical condition requiring use of pancreatic enzymes; daily, chronic, or regular use of proton pump inhibitors (PPIs); or histamine 2 (H2) receptor antagonists. Participants who intermittently use these medications, must meet the following criteria:
• •* No use of PPIs within 5 days before the first dose of alisertib.
• •* No use of H2 antagonist or pancreatic enzymes within 24 hours before the first dose of alisertib.
• •5. Inadequate bone marrow or other organ function (excluding hepatic impairment per eligibility criteria).
• •6. Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period or a positive urine pregnancy test on Day 1 before first dose of alisertib.
• •7. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
• •8. Treatment with any anticancer therapy or any investigational products within 3 weeks before the first dose of study drug.
• •9. Exposure to nitrosoureas or mitomycin C within 42 days before the first dose of study drug.
• •10. Radiotherapy within 14 days before the first dose of study drug.
• •11. Prior treatment with radiation therapy involving ≥ 25% of the hematopoietically active bone marrow within 42 days before the first dose of study drug.
• •12. Major surgery within 14 days before the first dose of study drug.
• •13. Serious infection within 14 days before the first dose of study drug. Participant must have recovered from infection before first dose.
• •14. Life-threatening illness unrelated to cancer.
• •15. Symptomatic brain metastasis. Participants with brain metastases:
• •* Must have stable neurologic status following local therapy (surgery or radiation) for at least 2 weeks after completion of the definitive therapy AND
• •* Must be without neurologic dysfunction that would confound the evaluation of neurologic or other adverse events (AEs).
• •16. Clinically significant coagulopathy or bleeding disorder.
• •17. Severe central nervous system, pulmonary, or renal disease not related to the participant's cancer.
• •18. Known human immunodeficiency virus (HIV) positive.
• •19. Known history of hepatitis C infection or suspected currently active hepatitis C infection, or known or suspected history of hepatitis B infection. Participants with known or suspected history of hepatitis B infection were to be screened and excluded when any of the following conditions were met:
• •* Received hematopoietic stem cell transplantation (either allogeneic or autologous), or
• •* Received any rituximab-containing treatment regimen in the last 12 months before entering the study, or
• •* Tested positive for the presence of at least 1 of the following 3 markers in blood (evaluated at Screening): hepatitis B surface antigen (HBsAg), antibodies against hepatitis B core antigen (anti-HBc), or hepatitis B virus deoxyribonucleic acid (HBV DNA).
• •20. Any of the following cardiovascular conditions:
• •* Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure, angina, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
• •* Corrected QT interval (QTc) \> 500 milliseconds in a 12-lead electrocardiogram (ECG) during screening.
• •21. History of uncontrolled sleep apnea syndrome or other condition that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease.
• •22. Use of moderate or strong cytochrome P450 (CYP) 3A inhibitors or CYP3A inducers within 2 weeks before the first dose of study drug.