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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 128
- 主要终点
- Progression-free Survival (PFS) Based on Central Independent Review
研究概览
简要总结
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.
详细描述
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)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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).
干预措施: TAS-114 (Drug)
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).
干预措施: S-1 (Drug)
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).
干预措施: S-1 (Drug)
结局指标
主要结局
Progression-free Survival (PFS) Based on Central Independent Review
时间窗: From date of randomization or until date of disease progression or death whichever occurred first (approximately up to 13 months)
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.
次要结局
- 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))
- Overall Survival (OS)(From date of randomization until death (approximately up to 15 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))
- 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))
- 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))