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

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

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

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors (Excluding Breast Cancer)
• Intervention / Treatment: Drug: TAS-102; Drug: Placebo

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Has provided written informed consent
2. Has advanced solid tumors (excluding breast cancer) for which no standard therapy exists
3. Has received no more than 5 prior cancer therapies
4. ECOG performance status of 0 or 1
5. Is able to take medications orally
6. Corrected QT interval using Bazett's correction is no more than 450 msec on resting ECG
7. Has adequate organ function (bone marrow, kidney and liver)
8. 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:

1. 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
2. Certain serious illnesses or medical condition(s)
3. Has a family history of unexplained sudden death or long QT syndrome
4. Has had a documented cardiovascular complication following a fluoropyrimidine-derived treatment
5. Is a patient for whom it is not technically possible to obtain quality ECG tracings
6. Is receiving a concomitant drug that is known to affect QT interval or to be arrhythmogenic
7. Has unresolved toxicity of greater than or equal to CTCAE Grade 2 attributed to any prior therapies
8. Known sensitivity to TAS-102 or its components
9. Is a pregnant or lactating female
10. Refuses to use an adequate means of contraception (including male patients)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo tablets, orally, single dose.
Experimental: TAS-102	Drug: TAS-102; 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.

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Taiho Oncology, Inc.

Publications and helpful links

General Publications

• Bendell JC, Patel MR, Yoshida K, Seraj J, Weaver R, Lemech C, Todaro TG, Pant S, Arkenau HT. Phase 1 study of cardiac safety of TAS-102 in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2016 Jun;77(6):1275-83. doi: 10.1007/s00280-016-3031-9. Epub 2016 May 5.

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: May 24, 2013
• First Submitted That Met QC Criteria: May 29, 2013
• First Posted (Estimate): June 4, 2013

Study Record Updates

• Last Update Posted (Estimate): November 9, 2015
• Last Update Submitted That Met QC Criteria: November 6, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: Advanced solid tumors (excluding breast cancer) for which no standard therapy exists
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: TPU-TAS-102-103; 2013-000650-21 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No