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

Phase 1
18 Years
Not Enrolling
Advanced Malignancies

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Trial Information

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

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

- 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

- 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).

Type of Study:


Study Design:

Allocation: Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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.

Outcome Time Frame:

Duration of therapy

Safety Issue:


Principal Investigator

Medical Monitor

Investigator Role:

Study Director

Investigator Affiliation:

Millennium Pharmaceuticals, Inc.


United States: Food and Drug Administration

Study ID:




Start Date:

October 2007

Completion Date:

January 2011

Related Keywords:

  • Advanced Malignancies
  • Neoplasms