Status:
TERMINATED
A Phase 1 Trial of Extended MLN8054 Dosing in Patients With Advanced Malignancies
Lead Sponsor:
Millennium Pharmaceuticals, Inc.
Conditions:
Advanced Malignancies
Eligibility:
All Genders
18+ years
Phase:
PHASE1
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 p...
Eligibility Criteria
Inclusion
- 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
- Patients meeting any of the following exclusion criteria are not to be enrolled in the study:
- Pregnant or lactating
- Major surgery within the 21 days preceding the first dose of study treatment
- Infection requiring antibiotic therapy within the 7 days preceding the first dose of study treatment
- Life-threatening illness unrelated to cancer
- Ongoing nausea or vomiting greater than Grade 1 in severity. Patients who require ongoing treatment with metoclopramide to control nausea or vomiting, to the point that it is Grade 1 or less in severity, are allowed to participate in this trial.
- Diarrhea greater than Grade 1 in severity. 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 GI disease that could interfere with the oral absorption or tolerance of MLN8054
- Difficulty swallowing capsules
- Inability to remain nothing by mouth (NPO), except for water and prescribed medications, for 2 hours preceding and 2 hours following 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 greater than or equal to 25% of the hematopoietically active bone marrow
- Clinical and/or radiographic evidence of cerebral metastases. However, patients who have a history of CNS metastasis but have no radiographic or clinical evidence of residual tumor (eg, following complete surgical resection) are not excluded from participation in this study.
- Absolute neutrophil count \<1.5 x 106/ul; platelet count \<100 x 106/ul.
- Serum creatinine \>1.6 mg/dL or a measured or estimated (Cockcroft-Gault formula) creatinine clearance \<30 mL/minute
- Bilirubin \>1.25 times the upper limit of the normal range (ULN); aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \>2 times the ULN, and alkaline phosphatase (ALP) \>2 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 times the ULN.
- Abnormalities or arrhythmias on 12-lead electrocardiogram (ECG) that, in the opinion of the investigator, are considered to be clinically significant
- 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. A standard unit of alcohol is defined as one 12 oz beer, 1.5 oz of 80 proof alcohol, or one 6 oz glass of wine.
- Note: criteria 22, 23, and 24 apply only to patients in whom biopsy of tumor tissue is planned.
- aPTT and/or PT exceeding the ULN
- Known bleeding diathesis or history of abnormal bleeding
- Ongoing therapy with an anticoagulant (eg, aspirin, plavix, coumadin, heparin)
Key Trial Info
Start Date :
April 1 2006
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
April 1 2008
Estimated Enrollment :
44 Patients enrolled
Trial Details
Trial ID
NCT00652158
Start Date
April 1 2006
End Date
April 1 2008
Last Update
September 23 2013
Active Locations (1)
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1
Ciutat Sanitaria Vall d'Hebron
Barcelona, Spain, 08035