A Phase 1 Trial of Extended MLN8054 Dosing in Patients With Advanced Malignancies

NCT00652158 | Terminated Phase 1

• 1 other identifier: C10002
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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.

Conditions

Advanced Malignancies

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• 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

Study Arms (1)

A

EXPERIMENTAL

Drug: MLN8054

Interventions

MLN8054 DRUG

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

A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• \. 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

Study Sites (1)

Ciutat Sanitaria Vall d'Hebron

Barcelona, 08035, Spain

Location

MeSH Terms

Interventions

MLN8054

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2008
• First Posted: April 3, 2008
• Study Start: April 1, 2006
• Primary Completion: March 1, 2008
• Study Completion: April 1, 2008
• Last Updated: September 23, 2013

Record last verified: 2013-09

Locations

ES (1)