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

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

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: TAS-102

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 Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic
  • California
    • Duarte, California, United States, 91010
      • Duarte Clinical Site
    • Santa Monica, California, United States, 90404
      • Santa Monica Clinical Site
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Baltimore Clinical Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Boston Clinical Site
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinical Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • Pittsburgh Clinical Site
  • Texas
    • Dallas, Texas, United States, 75246
      • Dallas Clinical Site

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

1. Has provided written informed consent
2. Has advanced solid tumors (excluding breast cancer)
3. Has normal hepatic function, mild, moderate, or severe hepatic impairment
4. ECOG performance status of ≤2
5. Is able to take medications orally
6. Has adequate organ function
7. 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

1. Certain serious illnesses or medical condition(s)
2. 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
3. Has received TAS-102
4. Has unresolved toxicity of greater than or equal to CTCAE Grade 2 attributed to any prior therapies
5. Is a pregnant or lactating female

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK parameters of FTD, FTY, and TPI in plasma after a single 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	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
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

Collaborators and Investigators

• Sponsor: Taiho Oncology, Inc.

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: November 13, 2014
• First Submitted That Met QC Criteria: November 21, 2014
• First Posted (Estimate): November 25, 2014

Study Record Updates

• Last Update Posted (Actual): August 7, 2020
• Last Update Submitted That Met QC Criteria: August 6, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Liver Diseases; Hepatic; Advanced Solid Tumor; Liver Neoplasms; Pharmacologic Actions; Liver; mCRC; TAS-102; Liver Impairment; LFT
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: TO-TAS-102-106