Phase 1
N=3
Mass Balance, Pharmacokinetics and Metabolism Study of Alisertib
Advanced Solid Tumors · Lymphoma
Bottom Line
View on ClinicalTrials.gov: NCT01714947 ↗Enrolled (actual)
3
Serious AEs
0.0%
Results posted
Oct 2018
Primary outcome: Primary: Cmax: Maximum Observed Plasma Concentration for Alisertib and Drug-Related Material Following a Single Dose of [^14C]-Alisertib Oral Solution — 2183.3; 2606.7 nanomole (nmol)/liter (L)
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- [^14C]-alisertib (Drug); alisertib (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Millennium Pharmaceuticals, Inc.
- Primary completion
- Apr 2013
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Cmax: Maximum Observed Plasma Concentration for Alisertib and Drug-Related Material Following a Single Dose of [^14C]-Alisertib Oral Solution |
2183.3; 2606.7 | — |
| PRIMARY Tmax: Time of First Occurrence of Cmax for Alisertib and Drug-Related Material in Plasma Following a Single Dose of [^14C]-Alisertib Oral Solution |
1.00; 1.00 | — |
| PRIMARY 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 |
16800.0; 37033.3 | — |
| PRIMARY 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 |
17266.7; 42233.3 | — |
| PRIMARY T1/2: Terminal Half Life for Alisertib and Drug-Related Material in Plasma Following a Single Dose of [^14C]-Alisertib Oral Solution |
23.40; 42.03 | — |
| PRIMARY 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 |
4.06 | — |
| PRIMARY Ratio of Whole Blood Total Radioactivity (TRA) Cmax to Plasma TRA Cmax |
0.6550 | — |
| PRIMARY Ratio of Alisertib Plasma Cmax to Drug-Related Material TRA Plasma Cmax |
0.8397 | — |
| PRIMARY Ratio of Whole Blood TRA AUClast to Plasma TRA AUClast |
0.5950 | — |
| PRIMARY Ratio of Alisertib Plasma AUClast to Drug-Related Material TRA Plasma AUClast |
0.4997 | — |
| PRIMARY Ratio of Whole Blood TRA AUC∞ to Plasma TRA AUC∞ |
0.6750 | — |
| PRIMARY Ratio of Alisertib Plasma AUC∞ to Drug-Related Material TRA Plasma AUC∞ |
0.4490 | — |
| PRIMARY Fe: Fraction of Administered Dose of [^14C]-Alisertib Excreted in Urine |
2.650 | — |
| PRIMARY Fe: Fraction of Administered Dose of [^14C]-Alisertib Excreted in Feces |
87.833 | — |
| PRIMARY Ae: Amount of [^14C]-Alisertib Excreted in Urine |
939420.7 | — |
| PRIMARY Ae: Amount of [^14C]-Alisertib Excreted in Feces |
31156703.0 | — |
| PRIMARY Percent of Total Radioactivity (TRA) in Urine and Feces |
90.500 | — |
| PRIMARY Fe: Fraction of Administered Dose of Alisertib Excreted in Urine |
0.009045 | — |
| PRIMARY Ae: Amount of Alisertib Excretion in Urine |
3215.0 | — |
| PRIMARY Renal Clearance (CLR) of Alisertib |
0.000687 | — |
| SECONDARY Percentage of Alisertib Metabolites in Plasma Following a Single Dose of [^14C]-Alisertib Oral Solution |
12.0; 34.6; 5.6 | — |
| SECONDARY Percentage of Alisertib Metabolites in Urine Following a Single Dose of [^14C]-Alisertib Oral Solution |
0.24; 0.28; 0.66; 0.14; 0.84; 0.37 | — |
| SECONDARY Percentage of Alisertib Metabolites in Feces Following a Single Dose of [^14C]-Alisertib Oral Solution |
4.45; 1.19; 2.22; 2.96; 9.17; 1.72 | — |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events |
3; 0 | — |
| SECONDARY Number of Participants With Clinically Significant Changes or Abnormalities in Clinical Laboratory Values Reported as AEs |
1; 1; 1 | — |
| SECONDARY Number of Participants With Clinically Significant Changes or Abnormalities in Vital Sign Measurements |
— | — |
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.
Eligibility Criteria
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 exclusion criteria are not to be enrolled in the study:
- Female participants who are lactating or have a positive serum pregnancy test.
- Treatment with any investigational products or systemic antineoplastic treatment within 21 days before the first dose of alisertib.
- Medical conditions requiring daily, chronic, or regular use of proton pump inhibitors(PPIs) within 7 days preceding the first dose of alisertib, or H2-receptor antagonists within 24 hours preceding the first dose of alisertib.
- Participants requiring systemic anticoagulation (excluding low-dose aspirin, or low-dose anticoagulation to maintain patency of venous access devices). Low molecular weight heparin, administered as preventive treatment, is allowed if the participant has tolerated treatment with a stable dose and schedule without bleeding complications for more than 1 month.
- Major surgery within the 14 days preceding the first dose of alisertib.
- Infection requiring systemic intravenous (IV) antibiotic therapy within 14 days preceding the first dose of study drug, or other severe infection.
- Life-threatening or uncontrolled medical illness unrelated to cancer.
- Ongoing nausea or vomiting that is Grade 2 or worse in intensity.
- Diarrhea that is Grade 2 or worse in intensity or use of an antimotility agent to control diarrhea to an intensity of Grade 1 or lower level.
- Known GI disease or GI procedures that could interfere with the oral absorption, excretion, or tolerance of alisertib.
- History of urinary and/or fecal incontinence.
- History of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness such as severe chronic obstructive pulmonary disease.
- Inability to swallow tablets, or inability or unwillingness to avoid taking anything by mouth except for water and prescribed medications for 2 hours before and 1 hour after the first dose of alisertib.
- Inadequate bone marrow or other organ function as specified in study protocol.
- Any cardiovascular condition specified in the study protocol.
- Known or suspected human immunodeficiency virus (HIV) positive or hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection.
- Inability to comply with study visits and procedures including required inpatient confinement (approximately 11-17 days).
Please note that there are additional exclusion criteria. The study center will determine if you meet all of the criteria.
Data sourced from ClinicalTrials.gov (NCT01714947). 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.