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

Completed · Phase 1

Conditions studied: Advanced Solid Tumors, Relapsed/Refractory Lymphoma

In brief

The purpose of this study is to evaluate the effect of moderate or severe hepatic impairment on the single-dose pharmacokinetics of alisertib in adult participants with cancer.

Key facts

Study ID

NCT02214147

Run by

Millennium Pharmaceuticals, Inc.

People needed

36

Starts

2014-08-21

Expected to finish

2016-07-18

Last updated by the study team

2018-11-15

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.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.

You may not qualify if…

• 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 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.
• Inadequate bone marrow or other organ function (excluding hepatic impairment per eligibility criteria).
• 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.
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
• Treatment with any anticancer therapy or any investigational products within 3 weeks before the first dose of study drug.
• Exposure to nitrosoureas or mitomycin C within 42 days before the first dose of study drug.
• Radiotherapy within 14 days before the first dose of study drug.
• Prior treatment with radiation therapy involving ≥ 25% of the hematopoietically active bone marrow within 42 days before the first dose of study drug.
• Major surgery within 14 days before the first dose of study drug.
• Serious infection within 14 days before the first dose of study drug. Participant must have recovered from infection before first dose.
• Life-threatening illness unrelated to cancer.
• 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).
• Clinically significant coagulopathy or bleeding disorder.
• Severe central nervous system, pulmonary, or renal disease not related to the participant's cancer.
• Known human immunodeficiency virus (HIV) positive.
• 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

Where it is running

• Study site — Miami, Florida, United States
• Study site — Chicago, Illinois, United States
• Study site — Ann Arbor, Michigan, United States
• Study site — St Louis, Missouri, United States
• Study site — Dallas, Texas, United States
• Study site — Houston, Texas, United States
• Study site — San Antonio, Texas, United States

Full record on ClinicalTrials.gov

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