Mass Balance, Pharmacokinetics and Metabolism Study of Alisertib

Mass Balance, Pharmacokinetics, and Metabolism of [^14C]-Alisertib in Patients With Advanced Solid Tumors or Lymphomas

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01714947

Enrollment

Registered

2012-10-26

Start date

2013-01-24

Completion date

2013-06-14

Last updated

2018-10-31

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Advanced Solid Tumors, Lymphoma

Keywords

Drug Therapy

Brief summary

The purpose of this study is to assess the mass balance (i.e. cumulative excretion of total radioactivity \[TRA\] in urine and feces) of alisertib and pharmacokinetic (PK) of alisertib in plasma and urine, and of TRA in plasma and whole blood.

Detailed description

The drug being tested in this study is called alisertib (MLN8237). Alisertib is being tested to treat participants who have advanced solid tumors or lymphomas. This study looked at mass balance, pharmacokinetics (PK), metabolism, elimination and safety of alisertib. The study enrolled 3 patients. The study consisted of 2 parts: Part A and Part B. Participants received: * \[\^14C\]-alisertib 35 mg in Part A * alisertib 50 mg in Part B Participants were asked to take a single dose of \[\^14C\]-alisertib oral solution containing 80-100 μCi of total radioactivity (1.19-1.48 mCi/mmol) in Part A and alisertib 50 mg, orally, twice daily for 7 days in 21-day cycles until disease progression or unacceptable toxicity in Part B. This single center trial was conducted in United States. The overall time to participate in this study was up to 117 days. Participants remained confined to clinic in Part A and made multiple visits to the clinic in Part B. Participants were contacted 30 days after last dose of alisertib in Part A (if not continuing in Part B), or were contacted by telephone or a final visit 30 days after receiving their last dose of alisertib in Part B for a follow-up assessment.

Interventions

DRUG[^14C]-alisertib

\[\^14C\]-alisertib oral solution

DRUGalisertib

Alisertib enteric coated tablets

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

Each participants 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 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 0 or 1. * Expected survival longer than 3 months from enrollment in the study. * Radiographically or clinically evaluable tumor. * Suitable venous access for the conduct of blood sampling. * Recovered from the reversible effects of prior antineoplastic treatment (with the exception of alopecia and Grade 1 neuropathy). * Female participants who are postmenopausal for at least 1 year OR are surgically sterile OR if of childbearing potential, agree to practice 2 effective methods of contraception at the same time. * Male participants who agree to practice effective barrier contraception during the entire study and through 4 months after the last dose of study drug OR agree to abstain from heterosexual intercourse.

Exclusion criteria

Participants meeting any of the following

Design outcomes

Primary

Measure	Time frame
Renal Clearance (CLR) of Alisertib	Predose and multiple timepoints post-dose (up to 240 hours)
Fe: Fraction of Administered Dose of [^14C]-Alisertib Excreted in Feces	Predose and multiple timepoints post-dose (up to 240 hours)
Ae: Amount of [^14C]-Alisertib Excreted in Urine	Predose and multiple timepoints post-dose (up to 240 hours)
Ae: Amount of [^14C]-Alisertib Excreted in Feces	Predose and multiple timepoints post-dose (up to 240 hours)
Percent of Total Radioactivity (TRA) in Urine and Feces	Predose and multiple timepoints post-dose (up to 240 hours)
Fe: Fraction of Administered Dose of Alisertib Excreted in Urine	Predose and multiple timepoints post-dose (up to 240 hours)
Ae: Amount of Alisertib Excretion in Urine	Predose and multiple timepoints post-dose (up to 240 hours)
Cmax: Maximum Observed Plasma Concentration for Alisertib and Drug-Related Material Following a Single Dose of [^14C]-Alisertib Oral Solution	Predose and multiple timepoints post-dose (up to 240 hours)
Tmax: Time of First Occurrence of Cmax for Alisertib and Drug-Related Material in Plasma Following a Single Dose of [^14C]-Alisertib Oral Solution	Predose and multiple timepoints post-dose (up to 240 hours)
AUClast: Area Under the Concentration-Time Curve From Time 0 to Time of the Last Quantifiable Plasma Concentration for Alisertib and Drug-Related Material Following a Single Dose of [^14C]-Alisertib Oral Solution	Predose and multiple timepoints post-dose (up to 240 hours)
AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Plasma Concentration for Alisertib and Drug-Related Material Following a Single Dose of [^14C]-Alisertib Oral Solution	Predose and multiple timepoints post-dose (up to 240 hours)
T1/2: Terminal Half Life for Alisertib and Drug-Related Material in Plasma Following a Single Dose of [^14C]-Alisertib Oral Solution	Predose and multiple timepoints post-dose (up to 240 hours)
CL/F: Apparent Clearance After Extravascular Administration, Calculated Using the Observed Value of the Last Quantifiable Plasma Concentration for Alisertib Following a Single Dose of [^14C]-Alisertib Oral Solution	Predose and multiple timepoints post-dose (up to 240 hours)
Ratio of Whole Blood Total Radioactivity (TRA) Cmax to Plasma TRA Cmax	Predose and multiple timepoints post-dose (up to 240 hours)
Ratio of Alisertib Plasma Cmax to Drug-Related Material TRA Plasma Cmax	Predose and multiple timepoints post-dose (up to 240 hours)
Ratio of Whole Blood TRA AUClast to Plasma TRA AUClast	Predose and multiple timepoints post-dose (up to 240 hours)
Ratio of Alisertib Plasma AUClast to Drug-Related Material TRA Plasma AUClast	Predose and multiple timepoints post-dose (up to 240 hours)
Ratio of Whole Blood TRA AUC∞ to Plasma TRA AUC∞	Predose and multiple timepoints post-dose (up to 240 hours)
Ratio of Alisertib Plasma AUC∞ to Drug-Related Material TRA Plasma AUC∞	Predose and multiple timepoints post-dose (up to 240 hours)
Fe: Fraction of Administered Dose of [^14C]-Alisertib Excreted in Urine	Predose and multiple timepoints post-dose (up to 240 hours)

Secondary

Measure	Time frame	Description
Percentage of Alisertib Metabolites in Urine Following a Single Dose of [^14C]-Alisertib Oral Solution	Predose and multiple timepoints post-dose (0 to 192 hours)	Total radioactive peak distributions of metabolites in 0 to 192 hours pooled urine samples from participants.
Percentage of Alisertib Metabolites in Feces Following a Single Dose of [^14C]-Alisertib Oral Solution	Predose and multiple timepoints post-dose (0 to 192 hours)	Total radioactive peak distributions of metabolites in 0 to 192 hours pooled fecal samples from participants.
Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events	From first dose of study drug through 30 days after the last dose of study drug (Up to 117 days)	An Adverse Event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A Serious Adverse Event (SAE) was defined as any AE at any dose that: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in a persistent or significant disability/incapacity or resulted in congenital anomaly/birth defect. A treatment-emergent adverse event is defined as an adverse event with an onset that occurs after receiving study drug.
Number of Participants With Clinically Significant Changes or Abnormalities in Clinical Laboratory Values Reported as AEs	Part A: Day 1 and End of Study (EOS) Day 31 if not continuing to Part B, Part B: Days 8 and 15 of each cycle and EOS (Up to 117 days)	An abnormal laboratory was assessed to be an AE if the value lead to discontinuation or delay in treatment, dose modification, therapeutic intervention, or was considered by the investigator to be a clinically significant change from Baseline.
Number of Participants With Clinically Significant Changes or Abnormalities in Vital Sign Measurements	Part A: Day 1 and EOS (Day 31 if not continuing to Part B), Part B: Day 1 of each cycle and EOS (Up to 117 days)	Vital signs included body temperature, heart rate, and sitting blood pressure. The investigator determined if the changes were clinically significant.
Percentage of Alisertib Metabolites in Plasma Following a Single Dose of [^14C]-Alisertib Oral Solution	Predose and multiple timepoints post-dose (0 to 192 hours)	Total radioactive peak distributions of metabolites in 0 to 192 hours pooled plasma samples from participants.

Countries

United States

Participant flow

Recruitment details

Participants took part in the study at 1 investigative site in the United States from 24 January 2013 to 14 June 2013.

Pre-assignment details

Participants with a diagnosis of advanced solid tumors or lymphomas received \[\^14C\]-alisertib 35 mg oral solution single dose in Part A and alisertib 50 mg for 7 days in 21-day cycles in Part B.

Participants by arm

Arm	Count
Alisertib Part A: \[\^14C\]-alisertib 35 mg, oral solution containing 80 - 100 microcuries (μCi) of total radioactivity (1.19 - 1.48 mCi/mmol), orally, single dose on Day 1. Part B: Alisertib 50 mg, enteric coated tablets, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 3 Cycles).	3
Total	3

Withdrawals & dropouts

Period	Reason	FG000
Part B	Progressive Disease	3

Baseline characteristics

Characteristic	Alisertib
Age, Continuous	64.0 years STANDARD_DEVIATION 13.11
Body Mass Index (BMI)	26.91 kg/m^2 STANDARD_DEVIATION 8.346
Height	173.5 cm STANDARD_DEVIATION 7.15
Race/Ethnicity, Customized Black or African American	1 participants
Race/Ethnicity, Customized Not Hispanic or Latino	3 participants
Race/Ethnicity, Customized White	2 participants
Region of Enrollment United States	3 participants
Sex: Female, Male Female	1 Participants
Sex: Female, Male Male	2 Participants
Weight	80.27 kg STANDARD_DEVIATION 20.76

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	3 / 3
serious Total, serious adverse events	0 / 3