Food Effect Study of Alisertib (MLN8237) in Participants With Advanced Solid Tumors or Lymphomas

Phase 1

Completed

• Conditions: Advanced Solid Tumors; Lymphoma
• Interventions: Drug: Alisertib

• Registration Number: NCT01898078
• Lead Sponsor: Millennium Pharmaceuticals, Inc.

Brief Summary

The purpose of this study is to evaluate the effect of food on the single-dose pharmacokinetics (PK) of alisertib administered as an enteric-coated tablet (ECT) formulation in participants with advanced solid tumors or lymphomas.

Detailed Description

The drug being tested in this study is called alisertib. Alisertib is being tested in adult participants with advanced solid tumors or lymphomas.

The study enrolled 26 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):

* Alisertib 50 mg Fed + Fasted

* Alisertib 50 mg Fasted + Fed

All participants will be asked to take one alisertib tablet (ECT), orally, with or without a standard high-fat breakfast Cycle 1, Day 1, with the respective alternate food intake condition (fasted to fed or fed to fasted) on Cycle 2, Day 1, each followed by 14-day rest period. Participants will take alisertib, ECT, orally BID on Days 4 to 10 of Cycles 1 and 2, each followed by 14-day rest period. From Cycle 3 onwards participants will continue taking alisertib 50 mg, ECT, orally, BID on Days 1-7, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity.

This multi-center trial conducted at 3 sites in the United States. Participants will make multiple visits to the clinic and plus a final visit after 30 days of receiving their last dose of drug for a follow-up assessment.

Study Timeline

• Study First Submitted: 2013-07-01
• Study First Submitted QC: 2013-07-09
• Study First Posted: 2013-07-12
• Study Start: 2013-07-16
• Primary Completion: 2014-03-05
• Study Completion: 2017-01-24
• Results First Submitted: 2018-02-21
• Status Verified: 2019-03
• Results First Submitted QC: 2019-03-26
• Last Update Submitted: 2019-03-26
• Results First Posted: 2019-06-21
• Last Update Posted: 2019-06-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 26

Inclusion Criteria

• 18 years or older
• Histologically or cytologically confirmed advanced 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
• Participant must meet protocol-specified laboratory values
• Suitable venous access
• 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 or agree to practice true abstinence
• 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 practice true abstinence

Exclusion Criteria

• Prior or current investigational therapies within 4 weeks before the first dose of alisertib
• Female participants who are lactating or pregnant
• Participant requiring treatment with clinically significant enzyme inducers, such as the enzyme-inducing antiepileptic drugs phenytoin, carbamazepine, or phenobarbital, or rifampin, rifabutin, rifapentine, or St. John's wort within 14 days before the first dose of alisertib and during the study
• Medical conditions requiring daily, chronic, or regular use of proton pump inhibitors (PPIs) within 7 days preceding the first dose of alisertib, or histamine (H2)-receptor antagonists
• Participant requiring systemic anticoagulation
• Ongoing nausea or vomiting that is Grade 2 or worse in intensity
• Known gastrointestinal (GI) disease or GI procedures that could interfere with the oral absorption, excretion, or tolerance of alisertib
• History of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness such as severe chronic obstructive pulmonary disease
• Known or suspected human immunodeficiency virus (HIV) positive or hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection
• Participant who are lactose-intolerant or are unwilling/unable to consume the protocol specified standardized high-fat breakfast

Other protocol-defined inclusion/exclusion criteria may apply

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Alisertib 50 mg Fasted + Fed	Alisertib	Alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 50 mg, ECT, orally, BID on Days 4 through 10, followed by a 14-day rest period in Cycle 1 (24-day cycles), followed by alisertib 50 mg, ECT, orally, in fed state, once on Day 1, followed by alisertib 50 mg, ECT, orally, BID on Days 4 through 10, followed by a 14-day rest period in Cycle 2, followed by alisertib 50 mg, ECT, orally, BID on Days 1-7, followed by a 14-day rest period in Cycle 3 and onwards (21-day cycles) until disease progression, occurrence of an unacceptable alisertib-related toxicity.
Alisertib 50 mg Fed + Fasted	Alisertib	Alisertib 50 mg, enteric-coated tablets (ECT), orally, in fed state, once on Day 1, followed by alisertib 50 mg, ECT, orally, twice daily (BID) on Days 4 through 10, followed by a 14-day rest period in Cycle 1 (24-day cycles), followed by alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 50 mg, ECT, orally, BID on Days 4 through 10, followed by a 14-day rest period in Cycle 2, followed by alisertib 50 mg, ECT, orally, BID on Days 1-7, followed by a 14-day rest period in Cycle 3 and onwards (21-day cycles) until disease progression, occurrence of an unacceptable alisertib-related toxicity.

Primary Outcome Measures

Name	Time	Method
Cmax: Maximum Observed Plasma Concentration of Alisertib	Cycles 1 and 2, Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
AUC(Last): Area Under the Plasma Concentration Curve From Time 0 to the Time of the Last Quantifiable Concentration of Alisertib	Cycles 1 and 2, Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
AUC∞: Area Under the Plasma Concentration Curve From Time 0 to Infinity of Alisertib	Cycles 1 and 2, Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	From first dose through 30 days after the last dose of study drug (up to 225 days)	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.
Number of Participants With Clinically Significant Change in Laboratory Parameters Reported as AEs	From first dose through 30 days after the last dose of study drug (up to 225 days)	The number of participants with any clinical significant change in safety laboratory values collected throughout the study.
Number of Participants With Clinically Significant Change in Vital Sign Reported as AEs	From first dose through 30 days after the last dose of study drug (up to 225 days)	The number of participants with any clinical significant change in vital signs (sitting diastolic and systolic blood pressure, heart rate, and temperature) were collected throughout the study.