Study to Evaluate the Cardiac Safety of… | Clinical Trial

Key information

Conditions

Advanced Solid Tumors (Excluding Breast Cancer)

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

About this study

This is a Phase 1, nonrandomized study to evaluate the cardiac safety of TAS-102 in patients with advanced solid tumors. The study is conducted in 2 phases: the cardiac safety evaluation phase to investigate cardiac repolarization and the cardiac safety profile (Cycle 1) and the extension phase to assess the safety profile and antitumor activity (subsequent cycles).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Has provided written informed consent
Has advanced solid tumors (excluding breast cancer) for which no standard therapy exists
Has received no more than 5 prior cancer therapies
ECOG performance status of 0 or 1
Is able to take medications orally
Corrected QT interval using Bazett's correction is no more than 450 msec on resting ECG
Has adequate organ function (bone marrow, kidney and liver)
Women of childbearing potential must have a negative pregnancy test and must agree to adequate birth control if conception is possible. Males must agree to adequate birth control.

Exclusion criteria

Has had certain other recent treatment e.g. major surgery, extended field radiation, anticancer therapy, received investigational agent, within the specified time frames prior to study drug administration
Certain serious illnesses or medical condition(s)
Has a family history of unexplained sudden death or long QT syndrome
Has had a documented cardiovascular complication following a fluoropyrimidine-derived treatment
Is a patient for whom it is not technically possible to obtain quality ECG tracings
Is receiving a concomitant drug that is known to affect QT interval or to be arrhythmogenic
Has unresolved toxicity of greater than or equal to CTCAE Grade 2 attributed to any prior therapies
Known sensitivity to TAS-102 or its components
Is a pregnant or lactating female
Refuses to use an adequate means of contraception (including male patients)

Treatment and study plan

TAS-102

Drug

35 mg/m2/dose, orally, twice daily on days 1-5 and 8-12 of each 28-day cycle. Number of cycles: until at least one of the discontinuation criteria is met.

Placebo

Drug

Placebo tablets, orally, single dose.

Primary outcomes

QTc interval

Time frame: Days -2, -1, 1, and 12 of Cycle 1

Predose (Day -2) to post-dose changes and absolute values in QTc interval after placebo (Day -1, Cycle 1), after a single dose of TAS-102 (Day 1, Cycle 1), and after multiple doses (Day 12, Cycle 1)

Secondary outcomes

Quantitative and Qualitative ECG parameters

Time frame: Days -2, -1, 1, and 12 of Cycle 1

Predose (Day -2) to postdose changes and absolute values in quantitative Holter ECG parameters (heart rate, RR, PR and QRS intervals) after placebo (Day -1, Cycle 1), after a single dose of TAS-102 (Day 1, Cycle 1), and after multiple doses (Day 12, Cycle 1). In addition, qualitative assessments of Holter ECG recordings will be performed.
Relationship between TAS-102 pharmacokinetics and its effect on cardiac repolarization

Time frame: Days 1 and 12 of Cycle 1

Pharmacokinetic samples are taken on Days 1 and 12 of Cycle 1. The relationship between plasma concentrations of TAS-102 and the change from baseline in QTc adjusted by placebo will be quantified using a linear mixed effect model approach.
Safety monitoring including adverse events, vital signs, and laboratory assessments

Time frame: Through 30 days following last administration of study medication or until initiation of new anticancer treatment

Standard safety monitoring and grading using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) will be used.
Tumor assessments using Response Evaluation Criteria in Solid Tumors (RECIST)

Time frame: Every 8 weeks through Cycle 6 (ie, through 24 weeks). Thereafter, assessments will be performed at least every 12 weeks according to site standard of care, until at least one of the treatment discontinuation criteria is met.

Sponsors and collaborators

Lead sponsor

Taiho Oncology, Inc.

Industry

Registry information

Official study title

A Phase 1 Study to Evaluate the Cardiac Safety of Orally Administered TAS-102 in Patients With Advanced Solid Tumors

Important dates

Study start: 2013
Primary completion: 2014
Study completion: 2015
First posted: Jun 4, 2013
Registry last updated: Sep 5, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed

Study Comparing the Bioavailability of TAS-102 Tablets to an Oral Solution Containing Equivalent Amounts of FTD and TPI

NCT01874522