Clinical trial NCT00249301 (phase 1, status: terminated)
Conditions: breast neoplasm, colon neoplasm, pancreatic neoplasm, bladder neoplasm
ICD codes: C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60
Drugs: mln8054
SMILES: OC(=O)C1=CC=C(NC2=NC=C3CN=C(C4=C(C=CC(Cl)=C4)C3=N2)C2=C(F)C=CC=C2F)C=C1
Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed metastatic and/or advanced solid
             tumors(including lymphomas) for which standard treatment does not offer or no longer
             offers curative or life-prolonging potential

          -  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 is not
             required for participation in this study

          -  Suitable venous access for the conduct of blood sampling for MLN8054 PK

          -  Recovered from the reversible effects of prior antineoplastic therapy 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. Patients
             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.
             Patients 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
             MLN8054 is given.

          -  Male patients 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) during the study and for 21 days after the last dose of
             study treatment.

          -  Female patients 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) during the study and for 21 days
             after the last dose of study treatment.

          -  Able to give informed consent before the conduct of any study-related procedure not
             part of normal medical care and to comply with the protocol

        Exclusion Criteria:

          -  Pregnant or lactating

          -  Major surgery within the 28 days preceding the first dose of study treatment

          -  Serious infection within the 28 days before the first dose of study treatment

          -  Life-threatening illness unrelated to cancer

          -  Ongoing nausea or vomiting of any severity

          -  > Grade 1 diarrhea

          -  Known GI disease that could interfere with the oral absorption or tolerance of MLN8054

          -  Difficulty swallowing capsules

          -  Inability to fast overnight before the morning dose of MLN8054 and to remain nothing
             by mouth ([NPO] except for water and prescribed medications) for 2 hours after each
             dose of MLN8054

          -  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 patients 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 (see Table 15-1 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 (CNS) metastasis but who have no radiographic
             or clinical evidence of residual tumor (eg, following complete surgical resection) are
             not excluded from participation in this study.

          -  Clinically significant abnormalities or arrhythmias on 12-lead electrocardiogram (ECG)
             in the opinion of the investigator

          -  Known or suspected human immunodeficiency virus (HIV) positive or hepatitis B surface
             antigen-positive status, or known or suspected active hepatitis C infection

          -  Known or suspected disorder of bilirubin metabolism or excretion, including, but not
             limited to, Gilbert's syndrome, Crigler-Najjar syndrome, Dubin-Johnson syndrome, and
             Rotor syndrome

          -  Inclusion in a trial of an investigational drug in the previous 4 weeks

          -  Admission of 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 21 days from the
             last dose of study treatment.