Advanced Nonhematologic Malignancies
Conditions
Keywords
TAK-733,, alisertib,, MLN8237,, Oral MEK Inhibitor,, Oral Aurora A Kinase Inhibitor
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
Interventions
DRUGTAK-733 and alisertib
TAK-733 will be administered orally once daily (QD) on Days 1 through 14 of the 21-day cycle. Alisertib will be administered orally twice daily (BID) on Days 1 through 7 of the 21-day cycle.
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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Adverse Events (AEs), Serious Adverse Events (SAEs), assessments of clinical laboratory values, and vital sign measurements | From signing of the informed consent form through 30 days after the last dose of study drug | To evaluate the safety profile and to determine DLTs, MTDs, and RP2D of oral TAK-733 + alisertib in patients with advanced nonhematologic malignancies |
| 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 | 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 | To characterize the single- and multiple-dose plasma PK of TAK-733 and alisertib in patients with advanced nonhematologic malignancies |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measures of disease response, including objective response rate and duration of response based on investigator's assessment using RECIST guidelines | 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 | To evaluate evidence of antitumor activity of TAK-733 + alisertib |
Countries
United States
Outcome results
None listed