Study of the Mass Balance of Oral FTD and TPI as Components of TAS-102 in Patients With Advanced Solid Tumors

NCT02031055 | Completed Phase 1

• 1 other identifier: TPU-TAS-102-108
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate, in patients with advanced solid tumors, the mass balance of FTD and TPI after a single dose of TAS-102 with a light tracer dose of \[14C\]FTD or \[14C\]TPI.

Conditions

Advanced Solid Tumors

Keywords

Advanced solid tumors

Outcome Measures

Primary Outcomes (4)

• Urinary, fecal, and respiratory excretion of 14C from FTD and urinary and fecal excretion of 14C from TPI

  Urine and feces samples will be collected at 24-hour intervals through 168 hours postdose. For \[14C\]FTD only, samples of CO2 will be trapped from expired air immediately prior to dosing (0 hour) and at 30 minutes, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose.

  Day 1 through day 8 (through 168 hours postdose)

• PK parameters of total radioactivity (AUC0-inf, AUC0-last, Cmax, Tmax, and T1/2) in whole blood and plasma after a single dose of TAS-102

  Blood will be collected immediately prior to dosing (0 hour) and at 30 minutes, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours postdose

• Metabolic profile of FTD and TPI in plasma, urine, and feces

  Characterization of FTD and TPI metabolites

  Blood will be collected immediately prior to dosing (0 hour) and at 30 minutes, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours postdose. Urine and feces samples will be collected at 24-hour intervals through 168 hours postdose.

• PK parameters of FTD, FTY, and TPI in plasma (Cmax, Tmax, AUC0-last, AUC0-inf, T1/2, CL/F, and Vd/F)

  Cmax, Tmax, AUC0-last, AUC0-inf, and T1/2 will be calculated for each analyte, and CL/F and Vd/F will be calculated for FTD and TPI

  Blood will be collected immediately prior to dosing (0 hour) and at 30 minutes, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours postdose.

Secondary Outcomes (2)

• 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, whichever comes first

• Tumor assessments using Response Evaluation Criteria in Solid Tumors (RECIST)

  Every 8 weeks during the extension phase through Cycle 6 (through 24 weeks) and at least every 12 weeks thereafter, until treatment discontinuation (ie, due to disease progression, AEs, patient death, physician decision, pregnancy, or patient request)

Study Arms (2)

TAS-102 with light tracer dose of [14C]FTD

EXPERIMENTAL

Drug: TAS-102 with a light tracer dose of [14C]FTD; Drug: TAS-102 tablets

TAS-102 with light tracer dose of [14C]TPI

EXPERIMENTAL

Drug: TAS-102 with a light tracer dose of [14C] TPI; Drug: TAS-102 tablets

Interventions

TAS-102 with a light tracer dose of [14C]FTD DRUG

A single dose of 60 mg TAS-102 with a light tracer dose (200 nCi, approximately 1.2 μg) of \[14C\]FTD administered as an oral solution on Day 1 (mass balance part)

Also known as: Oral Solution

TAS-102 with light tracer dose of [14C]FTD

TAS-102 with a light tracer dose of [14C] TPI DRUG

A single dose of 60 mg TAS-102 with a light tracer dose (1000 nCi, approximately 5.6 μg) of \[14C\]TPI administered as an oral solution on Day 1 (mass balance part)

Also known as: Oral solution

TAS-102 with light tracer dose of [14C]TPI

TAS-102 tablets 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. Treatment starts during study extension part (day 9 of the study).

TAS-102 with light tracer dose of [14C]FTD; TAS-102 with light tracer dose of [14C]TPI

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has advanced solid tumors (excluding previously treated breast cancer) for which no standard therapy exists
• ECOG performance status of 0 or 1
• Is able to take medications orally
• 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.

You may not qualify if:

• Has had certain other recent treatment e.g. anticancer therapy, received investigational agent, within the specified time frames prior to study drug administration
• Certain serious illnesses or medical condition(s)
• Has had either partial or total gastrectomy
• Has a medical condition that jeopardizes or impairs ability to collect representative excreta
• 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)
• Is an occupationally exposed worker as defined by relevant ionizing radiation regulations
• Has been exposed to 14C in the last 12 months

Sponsors & Collaborators

• Taiho Oncology, Inc.: lead

Study Sites (1)

University of Pittsbutgh Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Interventions

trifluridine tipiracil drug combination; Solutions

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations

Study Officials

• Jan H Beumer, PharmD, PhD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2013
• First Posted: January 9, 2014
• Study Start: February 1, 2014
• Primary Completion: November 1, 2014
• Study Completion: June 17, 2015
• Last Updated: September 5, 2024

Record last verified: 2024-08

Locations

US (1)