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

Taiho Oncology, Inc.128 enrolled

Overview

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.

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)

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

128

Conditions

Advanced or Metastatic Non-small Cell Lung Cancer

Interventions

TAS-114DRUG

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

S-1DRUG

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (30)

Unnamed facility

Loma Linda, California, United States

Unnamed facility

Gainesville, Florida, United States

Outcomes

Primary Outcomes

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.

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

Secondary Outcomes

Overall Survival (OS)

OS was defined as the time from the first dose of the study treatment to death from any cause. Participants who were alive at the end of study were censored at the last date the participant was known to be alive. OS was estimated from Kaplan-Meier method.

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

Overall Response Rate (ORR) Based on Central Independent Review

ORR was defined as the percentage of participants with objective evidence of complete response (CR) or partial response (PR) per response evaluation criteria in solid tumors (RECIST) version 1.1. CR was defined as the disappearance of all target lesions and non-target lesions and normalization of tumor marker level. Any pathological and non-pathological lymph nodes must have reduction in short axis to less than (\<) 10 mm. PR was defined as at least a 30 percent (%) decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum diameters.

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

Data from ClinicalTrials.gov

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