Clinical trial NCT02855125: A Randomized Phase 2 Trial of TAS-114 in Combination With S-1 Versus S-1
Official title: A Randomized, Open-Label, Multi-Center, International Phase 2 Study of TAS-114 in Combination With S-1 in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Advanced or Metastatic Non-small Cell Lung Cancer
Keywords: NSCLC
phase 2 study
TAS-114
S-1
Lead sponsor: Taiho Oncology, Inc.
Sponsor class: INDUSTRY
First posted: 2016-08-04
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)

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.

Primary outcomes:
measure: Progression-free Survival (PFS) Based on Central Independent Review
timeFrame: From date of randomization or until date of disease progression or death whichever occurred first (approximately up to 13 months)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From date of randomization until death (approximately up to 15 months)
measure: Overall Response Rate (ORR) Based on Central Independent Review
timeFrame: From date of first dose of study drug to the date of first documentation of progression or death (approximately up to 13 months)
measure: Disease Control Rate (DCR) Based on Central Independent Review
timeFrame: From date of first dose of study drug to the date of first documentation of progression or death (approximately up to 13 months)
measure: Duration of Response (DR) Based on Central Independent Review
timeFrame: From date of first response to the date of first documentation of progression or death (approximately up to 13 months)
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
timeFrame: From first dose of study drug up to 30 days after the last dose of study drug (approximately up to 13 months)
Other outcomes:
Locations:
city: Loma Linda
country: United States
state: California
city: Gainesville
country: United States
state: Florida
city: Cleveland
country: United States
state: Ohio
city: Portland
country: United States
state: Oregon
city: Dallas
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
city: Caen
country: France
city: Lille
country: France
city: Marseille
country: France
city: Paris
country: France
city: Pierre-Bénite
country: France
city: Villejuif
country: France
city: Catania
country: Italy
city: Milano
country: Italy
city: Palermo
country: Italy
city: Ravenna
country: Italy
city: Kashiwa
country: Japan
state: Chiba
city: Osakasayama
country: Japan
state: Osaka
city: Adachi
country: Japan
state: Saitama
city: Chuo-Ku
country: Japan
state: Tokyo
city: Koto-Ku
country: Japan
state: Tokyo
city: Sunto-Gun
country: Japan
state: Tokyo
city: Wakayama
country: Japan
city: Katowice
country: Poland
city: Lodz
country: Poland
city: Lublin
country: Poland
city: Warszawa
country: Poland
city: Badalona
country: Spain
city: Barcelona
country: Spain
city: Madrid
country: Spain
Study officials:
affiliation: Taiho Oncology, Inc. USA
name: Taiho Central
role: STUDY_DIRECTOR
References:
citation: 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.