Clinical trial NCT01898078: Food Effect Study of Alisertib (MLN8237) in Participants With Advanced Solid Tumors or Lymphomas
Official title: An Open-Label, Phase 1, Two-Way, Cross-Over Study of the Effect of the Food on the Pharmacokinetics of MLN8237 (Alisertib) in Patients With Advanced Solid Tumors or Lymphomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lymphoma
Keywords: MLN8237
Alisertib
Food effects
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2013-07-12
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Cmax: Maximum Observed Plasma Concentration of Alisertib
timeFrame: Cycles 1 and 2, Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
measure: AUC(Last): Area Under the Plasma Concentration Curve From Time 0 to the Time of the Last Quantifiable Concentration of Alisertib
timeFrame: Cycles 1 and 2, Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
measure: AUC∞: Area Under the Plasma Concentration Curve From Time 0 to Infinity of Alisertib
timeFrame: Cycles 1 and 2, Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Secondary outcomes:
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From first dose through 30 days after the last dose of study drug (up to 225 days)
measure: Number of Participants With Clinically Significant Change in Laboratory Parameters Reported as AEs
timeFrame: From first dose through 30 days after the last dose of study drug (up to 225 days)
measure: Number of Participants With Clinically Significant Change in Vital Sign Reported as AEs
timeFrame: From first dose through 30 days after the last dose of study drug (up to 225 days)
Other outcomes:
Locations:
city: Bronx
country: United States
state: New York
city: Nashville
country: United States
state: Tennessee
city: San Antonio
country: United States
state: Texas
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Monitor
role: STUDY_DIRECTOR
References: