Mass Balance, Pharmacokinetics and Metabolism Study of Alisertib

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01714947
Recruitment Status : Completed
First Posted : October 26, 2012
Last Update Posted : September 4, 2013
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.

Brief Summary:
This is a 2-part, open-label study in 4 to 6 evaluable patients with advanced solid tumors or lymphomas. This study is intended to provide a quantitative characterization of the mass balance, routes of metabolism, and excretion pathways of alisertib.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Lymphoma Drug: alisertib Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Mass Balance, Pharmacokinetics, and Metabolism of [14C]-Alisertib in Patients With Advanced Solid Tumors or Lymphomas
Study Start Date : January 2013
Actual Primary Completion Date : April 2013
Actual Study Completion Date : August 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
U.S. FDA Resources

Arm Intervention/treatment
Experimental: alisertib

Part A: Patients will receive a single dose of 35-mg [14C]-alisertib oral solution containing 80 - 100 μCi of total radioactivity (1.19 - 1.48 mCi/mmol). The estimated duration is approximately 10 days during which time the patient will remain at the clinical facility. The maximum number of days that a patient may remain in confinement is expected to be between 11 to 17 days.

Part B: Eligible patients from Part A may continue into Part B which will begin immediately after or within 2 weeks of the patient completing Part A (ie, when the patient has met the criteria to be discharged from the clinic). Patients will receive alisertib tablets administered orally at a dose of 50 mg twice daily for 7 days in 21-day cycles.

Drug: alisertib
Other Name: MLN8237

Primary Outcome Measures :
  1. Time to maximum plasma concentration [ Time Frame: Daily for approximately 10 days ]
    Pharmacokinetics of alisertib in plasma and total radioactivity in plasma and whole blood

  2. Percent urinary recovery [ Time Frame: Daily for approximately 10 days ]
  3. Alisertib excretion in urine [ Time Frame: Daily for approximately 10 days ]
  4. Percent fecal excretion [ Time Frame: Daily for approximately 10 days ]
  5. Percent of total radioactivity in urine and feces [ Time Frame: Daily for approximately 10 days ]

Secondary Outcome Measures :
  1. Amount of metabolites in plasma [ Time Frame: Daily for approximately 10 days ]
    Metabolite profiles

  2. Number of adverse events [ Time Frame: From first dose of study drug through 30 days after the last dose of study drug ]
    Adverse events (AEs), serious adverse events (SAEs), assessments of clinical laboratory values, and vital sign measurements

  3. Amount of metabolites in urine [ Time Frame: Daily for approximately 10 days ]
    Metabolite profiles

  4. Amount of metabolites in feces [ Time Frame: Daily for approximately 10 days ]
    Metabolite profiles

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

Each patient 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 patients 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 patients 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:

Patients meeting any of the following exclusion criteria are not to be enrolled in the study:

  • Female patients 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.
  • Patient 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 patient 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01714947

United States, Washington
Comprehensive Clinical Development
Tacoma, Washington, United States, 98418
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.

Responsible Party: Millennium Pharmaceuticals, Inc. Identifier: NCT01714947     History of Changes
Other Study ID Numbers: C14014
First Posted: October 26, 2012    Key Record Dates
Last Update Posted: September 4, 2013
Last Verified: September 2013

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases