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

Advanced Nonhematologic Malignancies Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01613261
• Other study ID #: C20002
• Secondary ID: 2012-000831-22
• Status: Withdrawn
• Phase: Phase 1
• First received: June 1, 2012
• Last updated: October 31, 2013
• Start date: August 2013
• Est. completion date: November 2015

Study information

• Verified date: October 2013
• Source: Millennium Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationSpain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: November 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Nonhematologic Malignancies
• Neoplasms

Intervention

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.

Locations

Country	Name	City	State
United States	South Texas Accelerated Research Therapeutics (START)	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Millennium Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Adverse Events (AEs), Serious Adverse Events (SAEs), assessments of clinical laboratory values, and vital sign measurements	To evaluate the safety profile and to determine DLTs, MTDs, and RP2D of oral TAK-733 + alisertib in patients with advanced nonhematologic malignancies	From signing of the informed consent form through 30 days after the last dose of study drug	Yes
Primary	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	To characterize the single- and multiple-dose plasma PK of TAK-733 and alisertib in patients with advanced nonhematologic malignancies	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	No
Secondary	Measures of disease response, including objective response rate and duration of response based on investigator's assessment using RECIST guidelines	To evaluate evidence of antitumor activity of TAK-733 + alisertib	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	No