A Phase I Study of TAS-102 in Patients With Advanced Solid Tumors With Hepatic Impairment

Sponsor

Taiho Oncology, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT02301104

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Study to evaluate the safety, tolerability, and pharmacokinetics of TAS-102 in patients with advanced solid tumors and varying degrees of hepatic impairment.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors	Drug: TAS-102	Phase 1

Detailed Description

This is a Phase 1, open-label study to evaluate the safety, tolerability, and pharmacokinetics of TAS-102 in patients with advanced solid tumors with varying degrees of hepatic impairment. The study is conducted in 2 parts: the Pharmacokinetic Part (Cycle 1) and the Extension Part (Cycles 2 and beyond). Patients may continue to receive treatment with TAS-102 during the study extension part only after completion of the Pharmacokinetic Part.

Study Design

Study Type:

Interventional

Actual Enrollment :

24 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1, Open-label Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TAS-102 in Patients With Advanced Solid Tumors and Varying Degrees of Hepatic Impairment.

Study Start Date :

Jan 1, 2015

Actual Primary Completion Date :

Jun 1, 2016

Actual Study Completion Date :

Jun 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mild Hepatic Impairment 35 mg/m2/dose of TAS-102 orally, twice daily on days 1-5 and days 8-12 of each 28-day cycle. Number of cycles: approximately 4 or until discontinuation criteria is met.	Drug: TAS-102
Experimental: Moderate Hepatic Impairment 35 mg/m2/dose of TAS-102 orally, twice daily on days 1-5 and days 8-12 of each 28-day cycle. Number of cycles: approximately 4 or until discontinuation criteria is met.	Drug: TAS-102
Experimental: Severe Hepatic Impairment 35 mg/m2/dose of TAS-102 orally, twice daily on days 1-5 and days 8-12 of each 28-day cycle. Number of cycles: approximately 4 or until discontinuation criteria is met. The dose level of severe cohort, if enrolled, will be determined based on the Interim Assessment of mild and moderate cohorts.	Drug: TAS-102
Experimental: Normal Hepatic Function 35 mg/m2/dose of TAS-102 orally, twice daily on days 1-5 and days 8-12 of each 28-day cycle. Number of cycles: approximately 4 or until discontinuation criteria is met.	Drug: TAS-102

Outcome Measures

Primary Outcome Measures

PK parameters of FTD, FTY, and TPI in plasma after a single dose of TAS-102 [Blood samples will be collected in Cycle 1 Day 1 and Day 12 at pre-dose, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours post AM dose of TAS-102]
FTD, FTY and TPI: pharmacokinetic parameters Cmax, Tmax, AUC0-last, AUC0-inf, and T1/2. FTD and TPI: CL/F, Vd/F of TAS-102
Safety monitoring including adverse events, vital signs, and laboratory assessments [Through 30 days following last administration of study medication or until initiation of new anticancer treatment]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion

Has provided written informed consent
Has advanced solid tumors (excluding breast cancer)
Has normal hepatic function, mild, moderate, or severe hepatic impairment
ECOG performance status of ≤2
Is able to take medications orally
Has adequate organ function
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

Certain serious illnesses or medical condition(s)
Has had certain other recent treatment e.g. major surgery, anticancer therapy, extended field radiation, received investigational agent, shunt in the liver within the specified time frames prior to study drug administration
Has received TAS-102
Has unresolved toxicity of greater than or equal to CTCAE Grade 2 attributed to any prior therapies
Is a pregnant or lactating female

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Scottsdale	Arizona	United States	85259
2	Duarte Clinical Site	Duarte	California	United States	91010
3	Santa Monica Clinical Site	Santa Monica	California	United States	90404
4	Baltimore Clinical Site	Baltimore	Maryland	United States	21231
5	Boston Clinical Site	Boston	Massachusetts	United States	02111
6	Cleveland Clinical Site	Cleveland	Ohio	United States	44195
7	Pittsburgh Clinical Site	Pittsburgh	Pennsylvania	United States	15232
8	Dallas Clinical Site	Dallas	Texas	United States	75246