Study of TAK-733 in Combination With Alisertib in Adult Patients With Advanced Nonhematologic Malignancies

Sponsor

Millennium Pharmaceuticals, Inc. (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT01613261

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Advanced Nonhematologic Malignancies	Drug: TAK-733 and alisertib	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Aug 1, 2013

Anticipated Primary Completion Date :

Sep 1, 2015

Anticipated Study Completion Date :

Nov 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TAK-733 and alisertib	Drug: TAK-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.

Arm

Intervention/Treatment

Experimental: TAK-733 and alisertib

Drug: TAK-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.

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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