Clinical trial NCT02259010: A Study to Evaluate the Effect of Itraconazole on the Pharmacokinetics of Alisertib in Participants With Advanced Solid Tumors or Relapsed/Refractory Lymphoma
Official title: A Phase 1 Study to Evaluate the Effect of Itraconazole, a Strong CYP3A Inhibitor, on the Pharmacokinetics of Alisertib (MLN8237) in Adult Patients With Advanced Solid Tumors or Relapsed/Refractory Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Relapsed/Refractory Lymphoma
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2014-10-08
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: This study will assess the effect of multi-dose administration of itraconazole on the single-dose pharmacokinetics (PK) of alisertib.

Detailed description: The drug being tested in this study is called alisertib. Alisertib is being tested in adult participants with advanced solid tumors or relapsed refactory lymphoma. The study will look at the effect of the pharmacokinetics (how the drug moves through the body) of alisertib in the presence and absence of itraconazole.

This is an open label study. Participants will receive:

* Alisertib tablets 30 mg in Part A and 50 mg in Part B
* Itraconazole oral solution 200 mg in Part A

Participation in Part A is approximately 25 days. Part B participation is repeating 21-day cycles. The maximum duration of treatment with alisertib will be 12 months (approximately 16 cycles) unless it is determined by the investigator, with agreement by the sponsor, that a participant would derive clinical benefit from continued treatment beyond 12 months.

This multi-center study will take place in the United States.

Eligibility criteria: Inclusion Criteria

1. Male and female participants 18 years of age or older.
2. Participants with histologic or cytologic diagnosis of advanced or metastatic solid tumors or lymphomas for which no curative or life-prolonging therapies exist.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Exclusion Criteria

1. Systemic treatment with moderate or strong CYP3A inhibitors or inducers must be discontinued at least 14 days before the first dose of alisertib, and the use of these agents is not permitted during the study (except for the protocol-specified administration of itraconazole).
2. Known gastrointestinal (GI) abnormality (including recurrent nausea or vomiting) or GI procedure that could interfere with or modify the oral absorption or tolerance of alisertib.
3. Known hypersensitivity or intolerance to itraconazole or similar class agents.

Primary outcomes:
measure: Cmax: Maximum Observed Concentration of Alisertib in Presence and Absence of Itraconazole in Part A
timeFrame: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
measure: AUC(Last): Area Under the Plasma Concentration Curve From Time 0 to the Time of the Last Quantifiable Concentration of Alisertib in Presence and Absence of Itraconazole in Part A
timeFrame: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
measure: AUC∞: Area Under the Plasma Concentration Curve From Time 0 to Infinity of Alisertib in Presence and Absence of Itraconazole in Part A
timeFrame: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
Secondary outcomes:
measure: CL/F: Oral Clearance of Alisertib in Presence and Absence of Itraconazole in Part A
timeFrame: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
measure: Tmax: Time to Reach Maximum Plasma Concentration of Alisertib in Presence and Absence of Itraconazole in Part A
timeFrame: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
measure: Terminal Phase Elimination Half-Life of Alisertib in Presence and Absence of Itraconazole in Part A
timeFrame: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
measure: Cmax: Maximum Observed Plasma Concentration for Alisertib Metabolites M1 and M2 in Presence and Absence of Itraconazole in Part A
timeFrame: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
measure: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib Metabolites M1 and M2 in Presence and Absence of Itraconazole in Part A
timeFrame: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
measure: AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Alisertib Metabolites M1 and M2 in Presence and Absence of Itraconazole in Part A
timeFrame: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: First dose of study drug to 30 days after the last dose of study drug (up to 12 months)
measure: Number of Participants With Abnormal Laboratory Values Reported as AEs
timeFrame: First dose of study drug to 30 days after the last dose of study drug (up to 12 months)
measure: Number of Participants With Clinically Significant Change in Weight Reported as AEs
timeFrame: First dose of study drug to 30 days after the last dose of study drug (up to 12 months)
measure: Number of Participants With Clinically Significant Change in Vital Sign Reported as AEs
timeFrame: First dose of study drug to 30 days after the last dose of study drug (up to 12 months)
Other outcomes:
Locations:
city: Saint Louis
country: United States
state: Missouri
city: Oklahoma City
country: United States
state: Oklahoma
city: Germantown
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
Study officials:
References: