Study of MLN8237 in Participants With Advanced Solid Tumors

• Status: Completed
• Trial end date: 2014-07-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Millennium Pharmaceuticals, Inc.
• Treatments: Pharmaceutical Solutions

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