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

NCT02855125 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: TAS-114-2012016-001806-40
• Study Type: interventional
• Target: 128
• Locations: 6 countries
• Sites: 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.

Conditions

Advanced or Metastatic Non-small Cell Lung Cancer

Keywords

NSCLC; phase 2 study; TAS-114; S-1

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS) Based on Central Independent Review

  Progression-free survival was defined as the time (in months) from the day of randomization to the start of radiologic disease progression or death (any cause), whichever occurred first. Response assessments were made based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1). As per RECIST 1.1 criteria, progressive disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). (Note: the appearance of one or more new lesions was also considered progressions). Participants who did not have disease progression or died were censored at the last known time that the participant was progression free.

  From date of randomization or until date of disease progression or death whichever occurred first (approximately up to 13 months)

Secondary Outcomes (5)

• Overall Survival (OS)

  From date of randomization until death (approximately up to 15 months)

• Overall Response Rate (ORR) Based on Central Independent Review

  From date of first dose of study drug to the date of first documentation of progression or death (approximately up to 13 months)

• Disease Control Rate (DCR) Based on Central Independent Review

  From date of first dose of study drug to the date of first documentation of progression or death (approximately up to 13 months)

• Duration of Response (DR) Based on Central Independent Review

  From date of first response to the date of first documentation of progression or death (approximately up to 13 months)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

  From first dose of study drug up to 30 days after the last dose of study drug (approximately up to 13 months)

Study Arms (2)

TAS-114 + S-1

ACTIVE COMPARATOR

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).

Drug: TAS-114; Drug: S-1

S-1 (Monotherapy)

ACTIVE COMPARATOR

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).

Drug: S-1

Interventions

TAS-114 DRUG

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

TAS-114 + S-1

S-1 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); TAS-114 + S-1

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years old (≥ 20 years old in Japan);
• 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;
• 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
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria (Version 1.1, 2009);
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;
• Predicted life expectancy of at least 3 months;
• Able to take medications orally;
• Adequate organ function
• 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.
• Willing and able to comply with required scheduled visits and study procedures.

You may not qualify if:

• 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.
• A serious illness or medical condition
• 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
• Known hypersensitivity to S-1 or its metabolites (eg, 5-FU);
• Previous use of TAS-114, S-1, and 5-FU drugs;
• A pregnant or lactating female or possibly pregnant women, or men or women wishing to have children during the study period;
• A judgment of the investigator that the patient is inappropriate for study participation.

Sponsors & Collaborators

• Taiho Oncology, Inc.: lead

Study Sites (30)

Unknown Facility

Loma Linda, California, United States

Location

Unknown Facility

Gainesville, Florida, United States

Location

Unknown Facility

Cleveland, Ohio, United States

Location

Unknown Facility

Portland, Oregon, United States

Location

Unknown Facility

Dallas, Texas, United States

Location

Unknown Facility

Seattle, Washington, United States

Location

Unknown Facility

Caen, France

Location

Unknown Facility

Lille, France

Location

Unknown Facility

Marseille, France

Location

Unknown Facility

Paris, France

Location

Unknown Facility

Pierre-Bénite, France

Location

Unknown Facility

Villejuif, France

Location

Unknown Facility

Catania, Italy

Location

Unknown Facility

Milan, Italy

Location

Unknown Facility

Palermo, Italy

Location

Unknown Facility

Ravenna, Italy

Location

Unknown Facility

Kashiwa, Chiba, Japan

Location

Unknown Facility

Sayama, Osaka, 589-8511, Japan

Location

Unknown Facility

Adachi, Saitama, 362-0806, Japan

Location

Unknown Facility

Chuo-Ku, Tokyo, Japan

Location

Unknown Facility

Koto-Ku, Tokyo, 135-8550, Japan

Location

Unknown Facility

Sunto-Gun, Tokyo, Japan

Location

Unknown Facility

Wakayama, 641-8509, Japan

Location

Unknown Facility

Katowice, Poland

Location

Unknown Facility

Lodz, Poland

Location

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Lublin, Poland

Location

Unknown Facility

Warsaw, Poland

Location

Unknown Facility

Badalona, Spain

Location

Unknown Facility

Barcelona, Spain

Location

Unknown Facility

Madrid, Spain

Location

Related Publications (1)

• 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.

  PMID: 32246224 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

TAS-114; S 1 (combination)

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Taiho Central
• Organization: Taiho Oncology, Inc.

medicalinformation@taihooncology.com

+1 844-878-2446

Study Officials

• Taiho Central

  Taiho Oncology, Inc. USA

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2016
• First Posted: August 4, 2016
• Study Start: August 29, 2016
• Primary Completion: September 30, 2017
• Study Completion: November 30, 2017
• Last Updated: September 19, 2024
• Results First Posted: December 23, 2021

Record last verified: 2024-08

Locations

FR (6); JP (7); PL (4); US (6); IT (4); ES (3)