Advanced Malignancies
Conditions
Brief summary
This is a phase 1 clinical trial designed to evaluate increasing durations of MLN8054 oral dosing in patients with advanced malignancies. MLN8054 will be given once daily for 4 to 7 consecutive days per week for 2 to 3 weeks. Following the 2- to 3-week treatment period there will be a 2 week recovery period.
Interventions
DRUGMLN8054
10 mg doses of MLN8054 were given orally once daily following a schedule of 5 days on/2 days off/5 days on repeated every 28 days
Sponsors
Millennium Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Each patient must meet all of the following inclusion criteria to be enrolled in the study: * Has 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 (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 determination of MLN8054 plasma concentrations * Willingness to have serial skin punch biopsies obtained and, if feasible, to have serial biopsies of tumor tissue obtained before and following the first dose of MLN8054 Note: Once the relationship between drug exposure and inhibition of Aurora A kinase activity has been established, patients subsequently enrolled in the study will not be required to undergo either tumor or skin biopsies. 8\. Recovered from the reversible effects of prior antineoplastic therapy with at least 4 weeks elapsed since the last exposure to cytotoxic chemotherapy or 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 (ie, condoms) and inform any sexual partner that she must also use a reliable method of contraception (eg, a hormonal contraceptive, an intrauterine device, or diaphragm with spermicide) during the study and for 3 months 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 3 months after the last dose of study treatment. They should inform any male sexual partner to use an appropriate method of barrier contraception (ie, condoms) as well. * Able to give informed consent before the conduct of any study-related procedure not part of normal medical care and able to comply with the protocol
Exclusion criteria
Patients meeting any of the following
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Toxicities of MLN8054 therapy will be identified by continuous monitoring of adverse events, by at least once weekly assessment of laboratory values (hematology and clinical chemistry),and by periodic physical examinations and vital sign measurements | 12 - 18 months |
Secondary
| Measure | Time frame |
|---|---|
| Serial physical examinations, blood samples for tumor marker measurements, and radiographic evaluations will be used to assess the status of the patient's underlying disease | completion of every 2 cycles of MLN8054 treatment using theRECIST guidelines |
Countries
Spain
Outcome results
None listed