A Study of MLN8237, a Novel Aurora A Kinase Inhibitor, in Participants With Advanced Solid Tumors
Condition: Advanced Malignancies
MeSH terms: Neoplasms
Intervention: Alisertib
Intervention description: Alisertib (MLN8237) will be supplied in capsules of 5 or 25 mg and will be given on an empty stomach, with patients remaining nothing by mouth except for water and prescribed medications for 2 hours before and 1 hour after each dose. Each dose will be given by mouth with 8 ounces of water for 7 to 21 consecutive days. A 14-day recovery period will follow each dosing period regardless of its duration.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 87.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Drug therapy

Summary:

      To determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of MLN8237
      when given by mouth (PO) for a minimum of 7 and a maximum of 21 consecutive days, followed by
      a 14-day recovery period.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed metastatic and/or advanced solid tumors
             (including lymphomas) for which no effective standard treatment is available

          -  Aged 18 years or more

          -  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; however, measurable disease as defined
             by (RECIST) criteria is not required for participation in this study

          -  Suitable venous access for the conduct of blood sampling for MLN8237 PK

          -  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. Participants treated with fully
             human monoclonal antibodies must not have received treatment with such antibodies for
             at least 6 weeks, and those treated with chimeric monoclonal antibodies must not have
             received treatment with such antibodies for at least 4 weeks. Participants treated
             with noncytotoxic small molecule drugs (eg, tyrosine kinase inhibitors, such as
             Tarceva®, and hormonal agents, such as Femara®) must not have received treatment with
             these drugs for at least 2 weeks before the first dose of MLN8237 is given.

          -  Male participants must use an appropriate method of barrier contraception (eg,
             condoms) and inform any sexual partners that they must also use a reliable method of
             contraception (eg, birth control pills) from the time of informed consent until 3
             months after the last dose of study treatment.

          -  Female participants must be postmenopausal, surgically sterilized, or willing to use
             reliable methods of birth control (eg, a hormonal contraceptive, an intrauterine
             device, diaphragm with spermicide, or abstinence) and inform male sexual partners that
             they must also use a reliable method of contraception (eg, condoms) from the time of
             informed consent until 3 months after the last dose of study treatment.

          -  Willing and able to give written informed consent before the conduct of any study
             related procedure that is not part of normal medical care, and willing to comply with
             the protocol

        Exclusion Criteria:

          -  Pregnant or lactating

          -  Major surgery or serious infection within the 28 days preceding the first dose of
             study treatment

          -  Life-threatening illness or uncontrolled medical illness unrelated to cancer

          -  Ongoing nausea or vomiting of any severity

          -  > Grade 1 diarrhea

          -  Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral
             absorption or tolerance of MLN8237. Examples include but are not limited to partial
             gastrectomy, history of small intestine surgery, and celiac disease.

          -  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. There is no limit on the number of
             noncytotoxic therapies (eg, hormonal and immunologic) that participants may have
             received. Tyrosine kinase inhibitors (eg, Tarceva and Iressa®) are considered
             noncytotoxic compounds.

          -  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

          -  Clinical and/or radiographic evidence of cerebral metastases. However, participants
             who have a history of central nervous system (CNS) 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

          -  Absolute neutrophil count <1500/mm^3; platelet count <100,000/mm^3

          -  Serum creatinine >1.6 mg/dl or a measured or estimated creatinine clearance <40
             mL/minute

          -  Bilirubin >1.5 times the upper limit of the normal range (ULN); aspartate
             aminotransferase (AST)/alanine aminotransferase (ALT) >2.5 times the ULN, and alkaline
             phosphatase (ALP) >2.5 times the ULN. Both the AST and ALP may be elevated up to 5
             times the ULN if their elevation can be reasonably ascribed to the presence of
             metastatic disease to liver and/or to bone; however, the ALT must in all circumstances
             be <2.5 times the ULN

          -  Abnormalities on 12-lead electrocardiogram (ECG) 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)

          -  Left ventricular ejection fraction (LVEF) < 50%

          -  Known or suspected human immunodeficiency virus (HIV) positive or hepatitis B surface
             antigen-positive status, or known or suspected active hepatitis C infection. Testing
             for these agents is not required in the absence of clinical findings or suspicion.

          -  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. A standard unit of alcohol is defined as one 12-oz (150mL) beer, 1.5 oz
             (45mL) of 80-proof alcohol, or one 6-oz (175mL) glass of wine.

          -  Lactose intolerant, for the food effect cohort only.