A Trial of TAS-114 in Combination With S-1

Study Overview
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Brief Summary
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A Phase I, Open-Label, International, Multicenter, Non-Randomized, Dose-Escalating Safety, Tolerance and Pharmacokinetic Study of Oral Administration of TAS-114 in Combination with S-1 in a Twice Daily Schedule for 14 Days in Patients with Advanced Solid Tumors.

Detailed Description
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This is an open-label, non-randomized, dose-escalation Phase I study of TAS-114 administered in combination with S-1, evaluating the safety, tolerability, pharmacokinetics and preliminary antitumor activity of the TAS-114/S-1 regimen in patients with advanced solid tumors. The study will be conducted in two parts: a Dose-Escalation Phase (Part 1) to determine the MTD; and an Expansion Phase (Part 2) to further evaluate the safety and preliminary efficacy with the MTD. Patients will receive the study medication according to the proposed treatment schedule until disease progression (PD), occurrence of intolerable side effects, removal by the Investigator or withdrawal of consent. A patient is considered discontinued from study treatment when TAS-114 is discontinued. Male or female patients age 18 years or older with confirmed advanced solid tumor(s) for which no standard therapy exists. TAS-114/S-1 will be administered BID for 14 days followed by a 7-day recovery period, every 21 days (1 cycle) in patients with advanced solid tumors.

Official Title
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A Phase I, Open-Label, Non-Randomized, Dose-Escalating Safety, Tolerability and Pharmacokinetic Study of TAS-114 in Combination With S-1 in Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: TAS-114
* Drug: S-1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has provided written informed consent. Is ≥18 years of age Has histologically or cytologically confirmed advanced or metastatic solid tumor(s) for which no standard therapy exists. Expansion Phase only: Has at least one measurable lesion Is able to take medications orally (e.g., no feeding tube). Has adequate organ function Women of child-bearing potential must have a negative pregnancy test (urine or serum) within 7 days prior to starting the study drug. Is willing and able to comply with scheduled visits and study procedures. Exclusion Criteria: Has received treatment with any proscribed treatments within specified time frames prior to study drug administration. Has a serious illness or medical condition(s) Is receiving concomitant treatment with drugs that may interact with S-1

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation TAS-114 (PART 1)<br>Each cycle will be 21 days: 14 days of treatment and 7 days recovery. TAS-114 and S-1 will be escalated according to a defined dosing table and specific DLT criteria. | Drug: TAS-114<br>* TAS-114 is an inhibitor of dUTPase, a gatekeeper protein in pyrimidine-metabolism.<br>Drug: S-1<br>* S-1 is an oral antimetabolite; a combination of three pharmacological compounds: tegafur (FT), gimeracil (CDHP), and oteracil (Oxo)<br>|
| Experimental: Expansion phase TAS-114 (PART 2)<br>The TAS-114 and S-1 MTD established in the Dose Escalation Phase will be administered BID for 14 days followed by a 7 day recovery period. This regimen is repeated every 21 days thereafter. Approximately 40 to 60 evaluable patients will be enrolled in the Expansion Phase. PGx, PD and PK analysis will be performed based on specific criteria. | Drug: TAS-114<br>* TAS-114 is an inhibitor of dUTPase, a gatekeeper protein in pyrimidine-metabolism.<br>Drug: S-1<br>* S-1 is an oral antimetabolite; a combination of three pharmacological compounds: tegafur (FT), gimeracil (CDHP), and oteracil (Oxo)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identify Maximum Tolerated Dose (MTD) in mg/kg | To investigate the safety and determine the maximum tolerated dose (MTD) of TAS-114 in combination with S-1 in patients with advanced solid tumor(s) for which no standard therapy exists. | Up to 2.5 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Solid Tumors, Phase I, Pharmacokinetics, Pharmacodynamics, MTD