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

Sponsor

Taiho Oncology, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT02454062

Collaborator

(none)

120

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors	Drug: TAS-114 Drug: S-1	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

120 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Mar 1, 2013

Actual Primary Completion Date :

Dec 27, 2016

Actual Study Completion Date :

Sep 30, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose Escalation TAS-114 (PART 1) 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 TAS-114 is an inhibitor of dUTPase, a gatekeeper protein in pyrimidine-metabolism. Drug: S-1 S-1 is an oral antimetabolite; a combination of three pharmacological compounds: tegafur (FT), gimeracil (CDHP), and oteracil (Oxo)
Experimental: Expansion phase TAS-114 (PART 2) 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 TAS-114 is an inhibitor of dUTPase, a gatekeeper protein in pyrimidine-metabolism. Drug: S-1 S-1 is an oral antimetabolite; a combination of three pharmacological compounds: tegafur (FT), gimeracil (CDHP), and oteracil (Oxo)

Arm

Intervention/Treatment

Experimental: Dose Escalation TAS-114 (PART 1)

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

TAS-114 is an inhibitor of dUTPase, a gatekeeper protein in pyrimidine-metabolism.

Drug: S-1

S-1 is an oral antimetabolite; a combination of three pharmacological compounds: tegafur (FT), gimeracil (CDHP), and oteracil (Oxo)

Experimental: Expansion phase TAS-114 (PART 2)

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

TAS-114 is an inhibitor of dUTPase, a gatekeeper protein in pyrimidine-metabolism.

Drug: S-1

S-1 is an oral antimetabolite; a combination of three pharmacological compounds: tegafur (FT), gimeracil (CDHP), and oteracil (Oxo)

Outcome Measures

Primary Outcome Measures

Identify Maximum Tolerated Dose (MTD) in mg/kg [Up to 2.5 Years]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Erasme University Hospital-ULB	Brussels	Belgium	1070
2	Institut Gustave Roussy	Villejuif	France	94805
3	IRCCS San Marino IST	Genoa	Italy	16132
4	Universita Vita-Salute San Raffaele	Milan	Italy	20132
5	IOSI Istituto Oncologico della Svizzera Italiana	Bellinzona	Switzerland	6500