A Study to Evaluate the Effect of Itraconazole on the Pharmacokinetics of Alisertib in Participants With Advanced Solid Tumors or Relapsed/Refractory Lymphoma

Back to results

Primary Purpose

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Alisertib

Itraconazole

About this trial

This is an interventional basic science trial for Advanced Solid Tumors

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria

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

Exclusion Criteria

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).
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.
Known hypersensitivity or intolerance to itraconazole or similar class agents.

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Part A: Alisertib 30 mg+Itraconazole; Part B: Alisertib 50 mg

Arm Description

All participants were to complete Part A prior to Part B. Part A: Alisertib 30 mg, tablets, orally, on Days 1 and 10 plus itraconazole, 200 mg, oral solution, once daily on Days 5 to 13. Part A and B were separated by a washout period of at least 10 days (and up to 4 weeks). Part B: Alisertib 50 mg, tablets, orally, twice daily, for 7 days in 21-day cycles until disease progression or unacceptable toxicity (up to 16 cycles).

Outcomes

Primary Outcome Measures

Cmax: Maximum Observed Concentration of Alisertib in Presence and Absence of Itraconazole in Part A

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

AUC∞: Area Under the Plasma Concentration Curve From Time 0 to Infinity of Alisertib in Presence and Absence of Itraconazole in Part A

Secondary Outcome Measures

CL/F: Oral Clearance of Alisertib in Presence and Absence of Itraconazole in Part A

Tmax: Time to Reach Maximum Plasma Concentration of Alisertib in Presence and Absence of Itraconazole in Part A

Terminal Phase Elimination Half-Life of Alisertib in Presence and Absence of Itraconazole in Part A

Cmax: Maximum Observed Plasma Concentration for Alisertib Metabolites M1 and M2 in Presence and Absence of Itraconazole in Part A

Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib Metabolites M1 and M2 in Presence and Absence of Itraconazole in Part A

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

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

An AE is considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A SAE is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.

Number of Participants With Abnormal Laboratory Values Reported as AEs

Standard safety laboratory tests included Chemistry and Hematology. Abnormal laboratory values that led to discontinuation or delay in treatment, dose modification, therapeutic intervention, or were considered by the investigator to be a clinically significant change from baseline were reported as AEs.

Number of Participants With Clinically Significant Change in Weight Reported as AEs

Change relative to baseline in participant's weight measured throughout study.

Number of Participants With Clinically Significant Change in Vital Sign Reported as AEs

Vital signs will include body temperature (oral), sitting blood pressure (after the participant has rested for at least 5 minutes), and pulse (bpm).

Full Information

NCT ID

NCT02259010

First Posted

October 3, 2014

Last Updated

August 16, 2019

Sponsor

Millennium Pharmaceuticals, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT02259010

Brief Title

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

2. Study Status

Record Verification Date

August 2019

Overall Recruitment Status

Completed

Study Start Date

October 22, 2014 (Actual)

Primary Completion Date

March 27, 2015 (Actual)

Study Completion Date

October 21, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Millennium Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

No

Data Monitoring Committee

No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Advanced Solid Tumors, Relapsed/Refractory Lymphoma

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part A: Alisertib 30 mg+Itraconazole; Part B: Alisertib 50 mg

Arm Type

Experimental

Arm Description

All participants were to complete Part A prior to Part B. Part A: Alisertib 30 mg, tablets, orally, on Days 1 and 10 plus itraconazole, 200 mg, oral solution, once daily on Days 5 to 13. Part A and B were separated by a washout period of at least 10 days (and up to 4 weeks). Part B: Alisertib 50 mg, tablets, orally, twice daily, for 7 days in 21-day cycles until disease progression or unacceptable toxicity (up to 16 cycles).

Intervention Type

Drug

Intervention Name(s)

Alisertib

Intervention Description

Alisertib tablets

Intervention Type

Drug

Intervention Name(s)

Itraconazole

Other Intervention Name(s)

SPORANOX®

Intervention Description

Itraconazole oral solution

Primary Outcome Measure Information:

Title

Cmax: Maximum Observed Concentration of Alisertib in Presence and Absence of Itraconazole in Part A

Time Frame