Phase 1 Completed N=53 Randomized Treatment

Study of MLN8237 in Participants With Advanced Solid Tumors

Source: ClinicalTrials.gov NCT00962091 ↗

Enrolled (actual)

Serious AEs

35.9%

Results posted

Mar 2019

Primary outcomePrimary: Part A: Dose-normalized Cmax (Maximum Observed Concentration) for Estimation of Relative Bioavailability for Alisertib Oral Solution (OS) Versus Powder in Capsule Formulations (PIC) — 58.78; 31.40 nM/mg

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.

Outcome Measures

Outcome	Result	p-value
PRIMARY Part A: Dose-normalized Cmax (Maximum Observed Concentration) for Estimation of Relative Bioavailability for Alisertib Oral Solution (OS) Versus Powder in Capsule Formulations (PIC)	58.78; 31.40	—
PRIMARY Part A: Dose-normalized AUClast (Area Under the Concentration-Time Curve From Time 0 to Time of the Last Quantifiable Concentration) for Estimation of Relative Bioavailability for Alisertib Oral Solution (OS) Versus Powder in Capsule Formulations (PIC)	530.18; 372.53	—
PRIMARY Part B: Cmax: Maximum Observed Concentration for Alisertib Administered as an Oral Solution With Food Versus Without Food	—	—
PRIMARY Part B: AUClast: Area Under the Concentration-Time Curve From Time 0 to Time of the Last Quantifiable Concentration for Alisertib Administered as an Oral Solution With Food Versus Without Food	—	—
PRIMARY Part B: Cmax: Maximum Plasma Concentration for Alisertib Oral Solution Following Multiple-Dose Administration	—	—
PRIMARY Part B: Tmax: Time of First Occurrence of Cmax Over the Dosing Interval for Alisertib Oral Solution Following Multiple-Dose Administration	—	—
PRIMARY Part B: AUCτ: Area Under the Concentration-Time Curve From Time 0 to End of Dosing Interval for Alisertib Oral Solution Following Multiple-Dose Administration	—	—
PRIMARY Part C: Cmax: Maximum Observed Concentration for Alisertib Administered as an Enteric-Coated Capsule (ECT) With Food Versus Without Food	1757.9; 1401.2	—
PRIMARY Part C: AUClast: Area Under the Concentration-Time Curve From Time 0 to Time of the Last Quantifiable Concentration for Alisertib Administered as an Enteric-Coated Capsule (ECT) With Food Versus Without Food	23928.6; 24135.0	—
PRIMARY Part C: AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Concentration for Alisertib Administered as an Enteric-Coated Capsule (ECT) With Food Versus Without Food	30627.3; 28507.1	—
PRIMARY Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	4; 19; 6; 24; 2; 4	—
PRIMARY Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5%	3; 8; 2; 21; 3; 7	—
PRIMARY Number of Participants With Abnormal Vital Signs Reported as Adverse Events	1; 0; 1; 1; 0; 1	—
SECONDARY Best Overall Response (CR+PR) Based on Investigator's Assessment According to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1	0; 0; 0; 0; 0; 0	—

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00962091). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.