Study to Evaluate the Cardiac Safety of TAS-102 in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the cardiac safety of TAS-102 in patients with advanced solid tumors.

Detailed Description
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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).

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

Conditions
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Advanced Solid Tumors (Excluding Breast Cancer)

Intervention / Treatment
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* Drug: TAS-102
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAS-102<br> | Drug: TAS-102<br>* 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.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo tablets, orally, single dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| QTc interval | 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) | Days -2, -1, 1, and 12 of Cycle 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantitative and Qualitative ECG parameters | 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. | Days -2, -1, 1, and 12 of Cycle 1 | 
| Relationship between TAS-102 pharmacokinetics and its effect on cardiac repolarization | 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. | Days 1 and 12 of Cycle 1 | 
| Safety monitoring including adverse events, vital signs, and laboratory assessments | Standard safety monitoring and grading using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) will be used. | Through 30 days following last administration of study medication or until initiation of new anticancer treatment | 
| Tumor assessments using Response Evaluation Criteria in Solid Tumors (RECIST) |  | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced solid tumors (excluding breast cancer) for which no standard therapy exists