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

Study Overview
=================
Brief Summary
-----------------
Study to evaluate the safety, tolerability, and pharmacokinetics of TAS-102 in patients with advanced solid tumors and varying degrees of renal impairment.

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 renal 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.

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 Renal Impairment

Conditions
-----------------
Advanced Solid Tumors

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Has provided written informed consent Has advanced solid tumors (excluding breast cancer) Has normal renal function, mild, moderate, or severe renal impairment and is not on dialysis 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, 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mild Renal Impairment<br>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<br> <br> |
| Experimental: Moderate Renal Impairment<br>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<br> <br> |
| Experimental: Severe Renal Impairment<br>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 will be determined based on the Interim Assessment of mild and moderate cohorts | Drug: TAS-102<br> <br> |
| Experimental: Normal Renal Function<br>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<br> <br> |

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, FTY, and TPI: Ae% and CLr. 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Renal, Kidney Diseases, Urologic Diseases, Renal Insufficiency, Renal Impairment, Pharmacokinetics, Advance Solid Tumor, Creatinine Clearance, Kidney Neoplasms, Renal Tumor, Kidney, Urology, Pharmacologic Action