A Randomized Phase 2 Trial of TAS-114 in Combination With S-1 Versus S-1

NCT ID: NCT02855125

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 128 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-29
• Study Completion Date: 2017-11-30

Brief Summary

This is a randomized, open-label, Phase 2 study of TAS-114 administered in combination with S-1, to investigate the efficacy, safety and tolerability of the TAS-114/S-1 regimen in patients with advanced or metastatic NSCLC.

The study will be conducted internationally in 2 regions: Asian [Japan] and Western [Europe and US]. Patients will be randomized into TAS-114/S-1 arm versus S-1 control arm in a 1:1 ratio.

Detailed Description

Randomization will take place once the consented patient has completed all the necessary baseline procedures and is deemed eligible for study entry. Treatment assignment will be done centrally using a dynamic allocation method (biased coin) via an interactive voice/web response system (IXRS) stratified by:

• Geographical region (Region 1: Asian [Japan]; Region 2: Western [Europe and US])
• Histological subtypes (nonsquamous cell carcinoma [including mixed] and squamous cell carcinoma)

Conditions

Advanced or Metastatic Non-small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

TAS-114 + S-1

Participants received 400 milligrams (mg) of TAS-114 tablets orally twice daily (BID) along with 30 milligrams per meter square (mg/m\^2) of S-1 capsule BID for 2 weeks (Day 1 to 14), followed by 1 week recovery period (Day 15 to 21) in each 21 days cycle, until progressive disease (PD), occurrence of intolerable side effects, removal by the Investigator, or withdrawal of consent (maximum treatment duration: 51 weeks).

Group Type: ACTIVE_COMPARATOR

TAS-114

Intervention Type: DRUG

TAS-114 was a modulator of 5-fluorouracil (5-FU).

S-1

Intervention Type: DRUG

S-1 was designed to provide oral delivery of 5-FU and to reduce the rate of degradation of 5-FU in vivo.

S-1 (Monotherapy)

Participants received 30 mg/m\^2 of S-1 capsules BID for 2 weeks (Day 1 to 14) followed by 1 week recovery period (Day 15 to 21) in each 21 days cycle, until progressive disease (PD), occurrence of intolerable side effects, removal by the Investigator, or withdrawal of consent (maximum treatment duration: 38 weeks).

Group Type: ACTIVE_COMPARATOR

S-1

Intervention Type: DRUG

S-1 was designed to provide oral delivery of 5-FU and to reduce the rate of degradation of 5-FU in vivo.

Interventions

TAS-114

TAS-114 was a modulator of 5-fluorouracil (5-FU).

Intervention Type: DRUG

S-1

S-1 was designed to provide oral delivery of 5-FU and to reduce the rate of degradation of 5-FU in vivo.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age ≥ 18 years old (≥ 20 years old in Japan);

2. Histologically diagnosed or cytologically proven advanced or metastatic NSCLC patients, either Stage IIIB/Stage IV disease (according to Version 7 of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology), or recurrent disease following radiation therapy or surgical resection;

3. Patients who had received at least 2 prior therapies for advanced or metastatic disease condition, including platinum doublet and pemetrexed, docetaxel, or immunotherapy, and were refractory to or unable to tolerate their last prior therapy

4. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria (Version 1.1, 2009);

5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;

6. Predicted life expectancy of at least 3 months;

7. Able to take medications orally;

8. Adequate organ function

9. Women of childbearing potential (WOCBP) must have a negative pregnancy test (urine or serum) within 7 days prior to starting the study drug. Both males and females must agree to use effective birth control during the study (prior to the first dose and for 6 months after the last dose) if conception is possible during this interval.

10. Willing and able to comply with required scheduled visits and study procedures.

Exclusion Criteria

1. Treatment with any of the following within the specified time frame prior to the study drug administration:

• Major surgery within prior 4 weeks and minor surgery within 7 days;
• Radiotherapy for extended field within prior 4 weeks or limited field within prior 2 weeks;
• Any anticancer therapy or investigational agent within prior 3 weeks.

2. A serious illness or medical condition

3. Concomitant treatment with the following drugs that may interact with S-1:

Sorivudine, brivudine, uracil, eniluracil, folinate/folinic acid, Cimetidine, dipyridamole, and nitroimidazoles, including metronidazole and misonidazoleMethotrexate, Clozapine,Allopurinol,Phenytoin,Flucytosine, a fluorinated pyrimidine antifungal agent,Coumarin-derivative anticoagulant

4. Known hypersensitivity to S-1 or its metabolites (eg, 5-FU);

5. Previous use of TAS-114, S-1, and 5-FU drugs;

6. A pregnant or lactating female or possibly pregnant women, or men or women wishing to have children during the study period;

7. A judgment of the investigator that the patient is inappropriate for study participation.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Taiho Oncology, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Taiho Central

Role: STUDY_DIRECTOR

Taiho Oncology, Inc. USA

Locations

Loma Linda, California, United States

Gainesville, Florida, United States

Cleveland, Ohio, United States

Portland, Oregon, United States

Dallas, Texas, United States

Seattle, Washington, United States

Caen, , France

Lille, , France

Marseille, , France

Paris, , France

Pierre-Bénite, , France

Villejuif, , France

Catania, , Italy

Milan, , Italy

Palermo, , Italy

Ravenna, , Italy

Kashiwa, Chiba, Japan

Sayama, Osaka, Japan

Adachi, Saitama, Japan

Chuo-Ku, Tokyo, Japan

Koto-Ku, Tokyo, Japan

Sunto-Gun, Tokyo, Japan

Wakayama, , Japan

Katowice, , Poland

Lodz, , Poland

Lublin, , Poland

Warsaw, , Poland

Badalona, , Spain

Barcelona, , Spain

Madrid, , Spain

Countries

United States; France; Italy; Japan; Poland; Spain

References

Yamamoto N, Hayashi H, Planchard D, Moran T, Gregorc V, Dowell J, Sakai H, Yoh K, Nishio M, Cortot AB, Benhadji KA, Soni N, Huang J, Makris L, Cedres S. A randomized, phase 2 study of deoxyuridine triphosphatase inhibitor, TAS-114, in combination with S-1 versus S-1 alone in patients with advanced non-small-cell lung cancer. Invest New Drugs. 2020 Oct;38(5):1588-1597. doi: 10.1007/s10637-020-00930-5. Epub 2020 Apr 3.

Reference Type: DERIVED

PMID: 32246224 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-001806-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

TAS-114-201

Identifier Type: -

Identifier Source: org_study_id