Study of MLN8237 in Participants With Advanced Solid Tumors
Condition: Advanced Solid Tumors
MeSH terms: Neoplasms
Intervention: Alisertib
Intervention description: Alisertib OS Alisertib PIC Alisertib PIC
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 53.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Drug therapy

Summary:

      The purposes of this study were to estimate the relative (Rel) bioavailability (BA) of an
      oral solution (OS) formulation of alisertib in reference to a powder-in-capsule (PIC)
      formulation, to characterize the effect of food on the single-dose pharmacokinetics (PK) of
      alisertib OS and enteric-coated tablets (ECT), to characterize the multiple-dose safety,
      tolerability, and steady-state PK of alisertib administered as an OS, and to characterize the
      multiple-dose safety and tolerability of alisertib administered as an ECT.
    

Eligibility criteria:

        Inclusion Criteria:

        Each participant must meet all of the following inclusion criteria to be enrolled in the
        study:

          -  18 years or older

          -  Histologically or cytologically confirmed metastatic and/or advanced solid tumor

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

          -  Female participants who are post menopausal, surgically sterile, or agree to practice
             2 effective methods of contraception or abstain from heterosexual intercourse

          -  Male participants who agree to practice effective barrier contraception or agree to
             abstain from heterosexual intercourse

          -  Voluntary written consent

          -  Suitable venous access for study-required blood sampling

          -  Measurable disease

          -  Recovered from effects of prior antineoplastic therapy

          -  Meet required entry laboratory and organ function levels

        Exclusion Criteria:

        Participants meeting any of the following exclusion criteria are not to be enrolled in the
        study:

          -  Female participants who are pregnant or lactating

          -  Serious medical or psychiatric illness that could interfere with protocol completion

          -  Major surgery within 14 days of first dose of alisertib

          -  Antineoplastic therapy, radiation therapy or any experimental therapy 21 days prior to
             first dose of alisertib

          -  Nitrosoureas or mitomycin-C within 6 weeks before the first dose of alisertib.

          -  Autologous stem cell transplant within 3 months before the first dose of alisertib, or
             prior allogeneic stem cell transplant at any time.

          -  Active infection requiring systemic therapy, or other serious infection

          -  Inability to swallow oral medication

          -  Gastrointestinal (GI) disease or GI procedure that could interfere with oral
             absorption or tolerance of alisertib

          -  Symptomatic brain metastasis

          -  Uncontrolled cardiovascular condition

          -  Diagnosis or treatment of another malignancy within 2 years preceding first dose of
             study drug except nonmelanoma skin cancer or in situ malignancy completely resected

          -  Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or
             hepatitis C

          -  Lactose-intolerant (Parts A and B only)

          -  Prior history of metabolic acidosis (Parts A and B only)

          -  Use of enzyme-inducing antiepileptic drugs such as phenytoin, carbamazepine or
             phenobarbital, or rifampin, rifabutin, rifapentine or St. John's wort within 14 days
             prior to the first dose of alisertib

          -  A medical condition requiring use of pancreatic enzymes; or daily, chronic , or
             regular use of proton pump inhibitors (PPI); or histamine (H2) receptor antagonists.
             Participants who intermittently use these medications must meet the following:

               -  No use of PPI within 7 days of first dose of alisertib

               -  No use of H2 antagonist or pancreatic enzymes within 24 hours of first dose of
                  alisertib

          -  Participants requiring full systemic anticoagulation