An Open-label, Randomized, Phase III Study Comparing Trifluridine/Tipiracil in Combination With Bevacizumab to Trifluridine/Tipiracil Monotherapy in Patients With Refractory Metastatic Colorectal Cancer (SUNLIGHT Study)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 492
- 试验地点
- 99
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
This study is designed as an international, open-label, controlled two-arm, randomized phase III comparison study evaluating the efficacy and safety of trifluridine/tipiracil in combination with bevacizumab versus trifluridine/tipiracil monotherapy in patients with refractory mCRC.
详细描述
This is an international, open-label, controlled two-arm, randomised phase III study evaluating the efficacy and safety of trifluridine/tipiracil in combination with bevacizumab versus trifluridine/tipiracil monotherapy in patients with refractory mCRC. The analysis will be done after 331 events are reported. In order to observe this number of events, 490 patients will be randomised (1:1) to receive trifluridine/tipiracil in combination with bevacizumab (experimental arm) or trifluridine/tipiracil monotherapy (control arm).
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
- •Has histologically confirmed unresectable adenocarcinoma of the colon or rectum (all other histological types are excluded).
- •RAS status must have been previously determined (mutant or wild-type) based on local assessment of tumor biopsy.
- •Has received a maximum of 2 prior chemotherapy regimens for the treatment of advanced colorectal cancer and had demonstrated progressive disease or intolerance to their last regimen.
- •Has measurable or non-measurable disease as defined by RECIST version 1.1
- •Is able to swallow oral tablets.
- •Estimated life expectancy ≥12 weeks.
- •Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1
排除标准
- •More than 2 prior chemotherapy regimens for the treatment of advanced colorectal cancer.
- •Pregnancy, lactating female or possibility of becoming pregnant during the study.
- •Patients currently receiving or having received anticancer therapies within 4 weeks prior to randomization.
- •Has not recovered from clinically relevant non-hematologic CTCAE grade ≥ 3 toxicity of previous anticancer therapy prior to randomization (excluding alopecia, and skin pigmentation).
- •Has symptomatic central nervous system metastases that are neurologically unstable or requiring increasing doses of steroids to control CNS disease.
- •Has severe or uncontrolled active acute or chronic infection.
- •Has active or history of interstitial lung disease and/or pneumonitis, or pulmonary hypertension.
- •Known Hepatitis B or Hepatitis C Virus infection.
- •Known carriers of HIV antibodies.
- •Confirmed uncontrolled arterial hypertension (defined as systolic blood pressure ≥ 150 mm Hg and/or diastolic blood pressure ≥ 100 mm Hg) or uncontrolled or symptomatic arrhythmia.
- •Deep arterial thromboembolic events including cerebrovascular accident or myocardial infarction within the last 6 months prior to randomization.
- •Treatment with any of the following within the specified time frame prior to randomization:
- •major surgery within 4 weeks prior to randomisation (the surgical incision should be fully healed prior to study drug administration), or has not recovered from side effects of previous surgery, or patient that may require major surgery during the study
- •Prior radiotherapy if completed less than 4 weeks before randomisation, except if provided as a short course for symptoms palliation only.
- •Drainage for ascites, pleural effusion or pericardial fluid within 4 weeks prior to randomization
- •Other clinically significant medical conditions.
- •Other malignancies.
研究组 & 干预措施
Trifluridine/Tipiracil + Bevacizumab
Participants were administered 35 milligrams per square meter per dose (mg/m²/dose) trifluridine/tipiracil (FTD/TPI) orally twice a day (BID), within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 an Day 13 to 14), over 2 weeks, followed by a 14-day rest; with bevacizumab (5 milligrams per kilogram [mg/kg], intravenous [IV] infusion administered every 2 weeks (Day 1 and Day 15). This treatment cycle was repeated every 4 weeks.
干预措施: Trifluridine/Tipiracil (Drug)
Trifluridine/Tipiracil + Bevacizumab
Participants were administered 35 milligrams per square meter per dose (mg/m²/dose) trifluridine/tipiracil (FTD/TPI) orally twice a day (BID), within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 an Day 13 to 14), over 2 weeks, followed by a 14-day rest; with bevacizumab (5 milligrams per kilogram [mg/kg], intravenous [IV] infusion administered every 2 weeks (Day 1 and Day 15). This treatment cycle was repeated every 4 weeks.
干预措施: Bevacizumab (Drug)
Trifluridine/Tipiracil
Participants were administered 35 mg/m²/dose of FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest. This treatment cycle was repeated every 4 weeks.
干预措施: Trifluridine/Tipiracil (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: From date of randomization to the death due to any cause or cut-off date, whichever comes first (maximum duration: up to 20 months)
Overall survival defined as the observed time elapsed between the date of randomization and the date of death due to any cause. The primary estimand of interest was defined to assess the effect of the randomized treatments on the survival duration in all participants regardless of whether or not intercurrent events had occurred (treatment policy strategy). Analysis was performed using Kaplan- Meier method.
Survival Probability at 6 Months
时间窗: From date of randomization until 6 months post treatment
Overall survival defined as the observed time elapsed between the date of randomization and the date of death due to any cause. The primary estimand of interest was defined to assess the effect of the randomized treatments on the survival duration in all participants regardless of whether or not intercurrent events had occurred (treatment policy strategy). Analysis was performed using Kaplan- Meier method. In this outcome measure, data of survival probability at 6 months was reported.
Survival Probability at 12 Months
时间窗: From date of randomization until 12 months post treatment
Overall survival defined as the observed time elapsed between the date of randomization and the date of death due to any cause. The primary estimand of interest was defined to assess the effect of the randomized treatments on the survival duration in all participants regardless of whether or not intercurrent events had occurred (treatment policy strategy). Analysis was performed using Kaplan- Meier method. In this outcome measure, data of survival probability at 12 months was reported.
Survival Probability at 18 Months
时间窗: From date of randomization until 18 months post treatment
Overall survival defined as the observed time elapsed between the date of randomization and the date of death due to any cause. The primary estimand of interest was defined to assess the effect of the randomized treatments on the survival duration in all participants regardless of whether or not intercurrent events had occurred (treatment policy strategy). Analysis was performed using Kaplan- Meier method. In this outcome measure, data of survival probability at 18 months was reported.
次要结局
- Progression Free Survival (PFS)(From randomization to the date of radiological tumour progression or death due to any cause or data cut-off date whichever comes first (i.e., up to 20 months))
- Probability of Participants With Progression Free Survival at 3, 6, 9 and 12 Months(From randomization until 3, 6, 9, and 12 months post treatment)
- Overall Response Rate (ORR)(From the date of randomization to the date of documentation of progression or death due to any cause or data cut-off, whichever occurred first (i.e., up to 20 months))
- Percentage of Participants With Disease Control(From randomization to the date of first documented tumor progression, death due to any cause or data cut-off date whichever comes first (i.e., up to 20 months))
- Number of Participants With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Events (TESAEs)(From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months))
- European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30): Time to Definitive Deterioration of >=10 Points in Sub-scale Scores - Kaplan-Meier Analysis(Date of randomization to first deterioration in QoL score >=10 points or death due to any cause, which ever occurred first (i.e., up to 20 months))
- European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30): Time to Definitive Deterioration of >=10 Points in the Global Health Status Score - Kaplan-Meier Analysis(Date of randomization to first deterioration in QoL score >=10 points or death due to any cause, which ever occurred first (i.e., up to 20 months))
- Change From Baseline in European Quality of Life Group Questionnaire With 5 Dimensions and 5 Levels Per Dimension (EQ-5D-5L): Health State Utility Index Value at Specified Timepoints(Baseline, Cycle 1, Cycle 2, Cycle 3, Cycle 4, Cycle 5, Cycle 6, Cycle 7, Cycle 8, Cycle 9, Cycle 10, Cycle 11, Cycle 12, Cycle 13 and Cycle 14)
- Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Score: Visual Analogic Scale (VAS) at Specified Timepoints(Baseline, Cycle 1, Cycle 2, Cycle 3, Cycle 4, Cycle 5, Cycle 6, Cycle 7, Cycle 8, Cycle 9, Cycle 10, Cycle 11, Cycle 12, Cycle 13 and Cycle 14)