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

Inclusion Criteria

• Male or female participants 18 years of age or older.
• Histologically or cytologically confirmed metastatic and/or advanced solid tumors or lymphomas for which standard curative or life-prolonging treatment does not exist or is no longer effective or tolerable.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Female participants who:
• Are post-menopausal for at least 1 year before the screening visit, OR
• Are surgically sterile, OR
• If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 30 days after the last dose of study drug, or agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant (periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception).
• Male participants, even if surgically sterilized (ie, status postvasectomy), who:
• Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug, or
• Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant (periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods for the female partner] and withdrawal are not acceptable methods of contraception).
• Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.
• Suitable venous access for the study-required blood sampling, including pharmacokinetics.
• Ability to swallow tablets.
• Participants with biliary obstruction for which a stent had been placed are eligible provided that the stent has been in place for more than 14 days before the first dose of alisertib and liver function has stabilized.
• Recovered from the reversible effects of prior antineoplastic therapy (ie, ≤ Grade 1 toxicity or baseline).
• Clinical laboratory values as specified below:
• Absolute neutrophil count (ANC) ≥ 1500/μL and platelet count ≥ 75,000/μL.
• Participants with normal hepatic function: Total bilirubin and alanine aminotransferase (ALT) must be ≤ upper limit of the normal range (ULN).
• Participants with moderate hepatic impairment: total bilirubin must be > 1.5 to 3 x ULN with any ALT level.
• Participants with severe hepatic impairment: total bilirubin must be > 3 x ULN with any ALT level.
• Measured creatinine clearance or calculated creatinine clearance > 30 mL/minute. Note: If a calculated creatinine clearance is used, it should be calculated according to the Cockcroft-Gault formula.
• Hemoglobin must be ≥ 8 g/dL.

Exclusion Criteria

• Participants of North/East Asian ethnicity (ie, Japanese, Chinese, Korean) will be excluded.
• 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.
• 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.
• A medical conditi