A Phase I Clinical and Pharmacodynamic Study of MLN8237, A Novel Aurora A Kinase Inhibitor, in Patients With Advanced Malignancies

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: NCT00651664
Recruitment Status : Completed
First Posted : April 3, 2008
Last Update Posted : November 18, 2013
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.

Brief Summary:
This is a multicenter, dose escalation, phase 1 study of MLN8237 in adult patients with advanced malignancies (excluding those with primary bone marrow involvement, such as leukemias and multiple myeloma).

Condition or disease Intervention/treatment Phase
Advanced Malignancies Drug: MLN8237 Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 59 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Clinical and Pharmacodynamic Study of MLN8237, A Novel Aurora A Kinase Inhibitor, in Patients With Advanced Malignancies
Study Start Date : October 2007
Actual Primary Completion Date : September 2010
Actual Study Completion Date : January 2011

Arm Intervention/treatment
Experimental: 1
Drug: MLN8237
MLN8237 will be administered orally once a day for 7 to 21 consecutive days followed by a 14-day recovery period.

Primary Outcome Measures :
  1. To determine the dose-limiting toxicity and maximum tolerated dose of MLN8237 when given by mouth for a minimum of 7 and a maximum of 21 days, followed by a 14-day recovery period. [ Time Frame: Duration of therapy ]

Secondary Outcome Measures :
  1. To describe the pharmacokinetics of MLN8237. [ Time Frame: Duration of therapy ]
  2. To evaluate the relationship between MLN8237 exposure and inhibition of Aurora A Kinase in tumor tissue and in the proliferating basal epithelial cells of the skin. [ Time Frame: Duration of therapy ]
  3. To describe any antitumor activity that may be observed with MLN8237 treatment. [ Time Frame: Duration of therapy ]

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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:

  • Have a histologically or cytologically confirmed metastatic and/or advanced malignancy (including lymphomas but excluding malignancies with extensive bone marrow involvement such as leukemias and multiple myeloma) for which standard treatment does not offer curative or life-prolonging potential
  • Aged 18 years or more
  • Eastern Cooperative Oncology Group performance status 0 or 1
  • Have an 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 therapy (with the exception of alopecia and grade 1 neuropathy) with at least 4 weeks elapsed since the last exposure to cytotoxic chemotherapy or to radiotherapy and at least 6 weeks elapsed since exposure to nitrosoureas or mitomycin C.
  • Male patients must use an appropriate method of barrier contraception and inform any sexual partners that they must also use a reliable method of contraception from the time of informed consent until 3 months after the last dose of study treatment.
  • Female patients must be postmenopausal at least 1 year, OR surgically sterile, OR if of childbearing potential, agree to 2 effective methods of nonhormonal contraception, or agree to completely abstain from heterosexual intercourse.
  • Able to give written consent.

Exclusion Criteria:

  • Pregnant or lactating
  • Major surgery or serious infection within the 28 days preceding the first dose of study treatment
  • Life-threatening or uncontrolled medical illness unrelated to cancer
  • Ongoing nausea or vomiting of any severity
  • > Grade 1 diarrhea. Patients who require ongoing therapy with an antimotility agent to control diarrhea to a Grade 1 or lower level are not allowed to participate in this trial
  • Known gastrointestinal disease or gastrointestinal procedures that could interfere with the oral absorption or tolerance of MLN8237.
  • History of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness such as severe chronic obstructive pulmonary disease.
  • Difficulty swallowing capsules
  • Inability to take nothing by mouth except for water and prescribed medications for 2 hours before and 1 hour after each dose of MLN8237
  • Received more than 4 previous cytotoxic chemotherapeutic regimens, including regimens used as adjuvant or neo-adjuvant therapies (in patients with metastatic breast cancer, a total of 5 previous cytotoxic chemotherapeutic regimens is permitted).
  • Prior treatment with high-dose chemotherapy, defined as chemotherapy requiring the use of peripheral blood or bone marrow stem cell support for hematopoietic reconstitution
  • Prior treatment with radiation therapy involving ≥25% of the hematopoietically active bone marrow for the distribution of active bone marrow in adults)
  • Clinical and/or radiographic evidence of cerebral metastases. However, patients who have a history of central nervous system metastasis but who have no radiographic or clinical evidence of residual tumor (eg, following complete surgical resection or stereotactic radiosurgery) are not excluded from participation in this study.
  • Abnormalities on 12-lead electrocardiogram considered by the investigator to be clinically significant or baseline prolongation of the rate-corrected QT interval(eg, repeated demonstration of QTc interval >450 milliseconds).
  • Known history of human immunodeficiency virus (HIV) infection, hepatitis B or hepatitis C.
  • Less than 4 weeks between the last dose of an investigational agent and the first dose of MLN8237.
  • Admission or evidence of benzodiazepine dependence or abuse and/or alcohol abuse or an inability to restrict consumption of alcohol to no more than 1 standard unit of alcohol per day during the study and for 30 days from the last dose of study treatment.
  • aPTT and/or PT exceeding the upper limit of the normal range
  • Known bleeding diathesis or history of abnormal bleeding
  • Ongoing therapy with an anticoagulant (e.g., aspirin, plavix, coumadin).

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): NCT00651664

Ciutat Sanitaria Vall d'Hebron - Servicio de Oncologia
Barcelona, Spain, 08035
H. Clínico Universitario de Valencia
Valencia, Spain
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.

Responsible Party: Millennium Pharmaceuticals, Inc. Identifier: NCT00651664     History of Changes
Other Study ID Numbers: C14002
First Posted: April 3, 2008    Key Record Dates
Last Update Posted: November 18, 2013
Last Verified: November 2013

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