Clinical trial NCT01613261: Study of TAK-733 in Combination With Alisertib in Adult Patients With Advanced Nonhematologic Malignancies
Official title: A Multicenter, Open-label, Phase 1b Study of TAK-733 (an Oral MEK Inhibitor) in Combination With Alisertib (an Oral Aurora A Kinase Inhibitor) in Adult Patients With Advanced Nonhematologic Malignancies
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Advanced Nonhematologic Malignancies
Keywords: TAK-733,
alisertib,
MLN8237,
Oral MEK Inhibitor,
Oral Aurora A Kinase Inhibitor
Lead sponsor: Millennium Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2012-06-07
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a Multicenter, Open-label, Phase 1b Study of TAK-733 in Combination With Alisertib in Adult Patients With Advanced Nonhematologic Malignancies


Eligibility criteria: Inclusion Criteria:

* Male or female patients 18 years or older
* Patients must have a diagnosis of a solid tumor malignancy for which standard, curative, or life-prolonging treatment does not exist or is no longer effective
* Radiographically or clinically evaluable tumor
* Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
* Female patients who are post menopausal for at least 1 year, surgically sterile, or agree to practice 2 effective methods of contraception through 30 days after the last dose of study drug or agree to abstain from heterosexual intercourse
* Male patients who agree to practice effective barrier contraception through 4 months after the last dose of alisertib or agree to abstain from heterosexual intercourse
* Voluntary written consent
* Clinical laboratory values as specified in the protocol

Exclusion Criteria:

* Female patients who are breastfeeding and lactating or pregnant
* Serious medical or psychiatric illness or laboratory abnormality that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol
* Treatment with any investigational products within 28 days before the first dose of study drug
* Prior treatment with Aurora A-targeted agents, including alisertib
* Prior treatment with MEK inhibitors, including TAK-733
* Prior treatment with BRAF inhibitors
* Systemic anticancer therapy within 21 days before the first dose
* Prior biologic or immunotherapy within 28 days before the first dose
* Major surgery or serious infection within 14 days before the first dose
* Life-threatening illness unrelated to cancer
* Known active infection with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C
* Cardiac condition as specified in study protocol or severe CNS, pulmonary, renal or hepatic disease
* Known GI conditions or GI procedure that could interfere with the oral absorption or tolerance of study drugs
* History of uncontrolled sleep apnea syndrome or other conditions that could result in excessive daytime sleepiness
* History of ongoing or a newly diagnosed eye abnormality
* Symptomatic brain metastases

Please note that there are additional inclusion and exclusion criteria. The study center will determine if you meet all of the criteria.

Site personnel will explain the trial in detail and answer any question you may have if you do qualify for the study. You can then decide whether or not you wish to participate. If you do not qualify for the trial, site personnel will explain the reasons

Primary outcomes:
measure: Number of Adverse Events (AEs), Serious Adverse Events (SAEs), assessments of clinical laboratory values, and vital sign measurements
timeFrame: From signing of the informed consent form through 30 days after the last dose of study drug
measure: TAK-733 and alisertib PK parameters including, but not limited to Cmax, Tmax, Area Under Curve (AUC), apparent oral clearance (CL/F), peak-to-trough ratio, and accumulation ratio
timeFrame: Escalation and MTD Refinement: Cycle 1-Day 1, 2, 7, 8, 14,and 15; Tumor Expansion Cohort: Cycle 1-Day 1, 7, 8, and 15; Cycle 2-Day 1, 8,and 15; PK Expansion Cohort: Cycle 1-Day 1, 7, and 8; Cycle 2-Day 7, 14, and 15. Each cycle is a 21 days cycle
Secondary outcomes:
measure: Measures of disease response, including objective response rate and duration of response based on investigator's assessment using RECIST guidelines
timeFrame: On screening; Cycle 2: between Day 15 and 21, and every third cycle thereafter (5,8,11 etc.) until progressive disease for approximately 1 year
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics (START)
state: Texas
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Monitor
role: STUDY_DIRECTOR
References: