Clinical trial NCT01449370: Dose Escalation Study of TAK-117 (MLN1117) in Subjects With Advanced Cancer
Official title: A Phase I, Dose Escalation Study of MLN1117 in Subjects With Advanced Solid Malignancies Followed by Expansion in Subjects With Measurable Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metastatic Solid Tumors
Keywords: INK1117
PIK3CA
KINASE
TUMOR
CANCER
Locally advanced or metastatic solid tumors
not eligible for standard of care therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2011-10-10
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the maximum tolerated dose (MTD) and/or optimal biologic dose(OBD), safety and tolerability, dose-limiting toxicity (DLT) of TAK-117 when administered orally in subjects with advanced solid malignancies.


Eligibility criteria: Inclusion Criteria:

* Subjects have had their PIK3CA gene mutation status assessed prior to enrolling into the study
* Subjects must have documented disease progression prior to enrolling into the study
* locally advanced or metastatic solid tumors with the exception of primary brain tumor, and have failed or are not eligible for standard of care therapy.
* Age greater than or equal to (\>=) 18 years, including males and females;
* Eastern cooperative oncology group (ECOG) performance status (PS) 0-1;
* Adequate organ function;
* Male subjects must be surgically sterile or must agree to use physician-approved contraception during the study and for 30 days following the last study drug administration;
* Ability to swallow oral medications;
* Ability to understand and willingness to sign informed consent prior to initiation of any study procedures;
* For women of child-bearing potential, negative serum pregnancy test within 14 days prior to the first study drug administration and use of physician-approved method of birth control from 30 days prior to the first study drug administration to 30 days following the last study drug administration

Exclusion Criteria:

* Diagnosis of primary brain tumor; untreated brain metastasis or history of leptomeningeal disease or spinal cord compression;
* Received prior cancer or other investigational therapy within 2 weeks prior to the first administration of study drug;
* Have received a systemic corticosteroid within one week prior to the first administration of study drug;
* Clinically significant cardiac disease;
* Myocardial infarction or unstable angina within 6 months prior to the first administration of study drug;
* Malabsorption ;
* Poorly controlled diabetes mellitus;
* Pregnancy (positive serum or urine pregnancy test) or breast feeding;
* Untreated brain metastasis or history of leptomeningeal disease or spinal cord compression;
* Failed to recover from the reversible effects of prior anticancer therapies;
* Have received a selective phosphoinositide-3-kinase alpha isoform (PI3K-alpha) inhibitor
* Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system (CNS) disease, active infection, or any other condition that could compromise the subject's participation in the study
* Known human immunodeficiency virus (HIV) infection
* Have a secondary malignancy within the last 3 years prior to first dose of study drug, excluding treated non-melanoma skin cancer, carcinoma in situ, or locally-treated prostate cancer

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of TAK-117
timeFrame: Baseline up to Cycle 1 Day 21
measure: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Death, Adverse Events (AEs) Leading to Discontinuation of Study Drug, and DLTs in Cycle 1
timeFrame: Baseline up to Cycle 27 Day 45
measure: Number of Participants With Highest Level of TEAEs Severity
timeFrame: Baseline up to Cycle 27 Day 45
measure: Number of Participants With Clinically Meaningful Changes in Laboratory Values
timeFrame: Baseline up to Cycle 27 Day 45
measure: Number of Participants With Clinically Meaningful Changes in Vital Signs
timeFrame: Baseline up to Cycle 27 day 45
measure: Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG)
timeFrame: Baseline up to Cycle 27 Day 45
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Cycle 1 Day 8 up to Cycle 27 Day 1 or disease progression or death
measure: Duration of Objective Response
timeFrame: Cycle 1 Day 8 up to Cycle 27 Day 1 or disease progression or death
measure: Clinical Benefit Rate (CBR)
timeFrame: Cycle 1 Day 8 up to Cycle 27 Day 1 or disease progression or death
measure: Cmax: Maximum Observed Plasma Concentration for TAK-117
timeFrame: Process A: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 24 hrs) post-dose; Process B: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 48 hrs) post-dose
measure: Ctrough: Observed Concentration at the End of Dosing Interval for TAK-117
timeFrame: Process A: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 24 hrs) post-dose; Process B: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 48 hrs) post-dose
measure: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-117
timeFrame: Process A: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 24 hrs) post-dose; Process B: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 48 hrs) post-dose
measure: T 1/2z: Terminal Disposition Phase Half-life for TAK-117
timeFrame: Process A: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 24 hrs) post-dose; Process B: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 48 hrs) post-dose
measure: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-117
timeFrame: Process A: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 24 hrs) post-dose; Process B: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 48 hrs) post-dose
measure: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-117
timeFrame: Process A: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 24 hrs) post-dose; Process B: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 48 hrs) post-dose
measure: %AUC Extrapolated: Percentage of Area Under Concentration-extrapolated
timeFrame: Process A: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 24 hrs) post-dose; Process B: Cycle 1 Day 1 pre-dose and at multiple timepoints (up to 48 hrs) post-dose
measure: Percent Change From Baseline in Pharmacodynamic Markers
timeFrame: Cycle 1 Day 8
Other outcomes:
Locations:
city: Boston
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Dallas
country: United States
state: Texas
city: Barcelona
country: Spain
city: Sutton
country: United Kingdom
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Monitor
role: STUDY_DIRECTOR
References: