A Phase 2 Study With Safety Lead-in, Evaluating TAS-102 Plus Nivolumab in Patients With Microsatellite Stable Refractory Metastatic Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 3
- 主要终点
- Immune-Related Overall Response Rate (irORR)
研究概览
简要总结
A Phase 2 Study with Safety Lead-in, Evaluating TAS-102 Plus Nivolumab in Participants with Microsatellite Stable Refractory Metastatic Colorectal Cancer
详细描述
This is a multicenter, single arm, safety lead-in, Phase 2 study, using Simon's 2 stage design evaluating the safety and efficacy of TAS-102 plus nivolumab in participants with Microsatellite-stable refractory metastatic colorectal cancer
Stage 1: Participants will be enrolled and after Cycle 1 treatment, they will be evaluated for the safety and tolerability of the combination therapy. Assuming a tolerated dose is confirmed additional participants evaluable for response will be enrolled and followed for a minimum of 6 months and there will be an interim analysis to assess the safety and efficacy to determine whether the second stage will open for enrollment.
Stage 2: Additional participant evaluable for response assessment will be enrolled and followed for a minimum of 6 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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 provided written informed consent.
- •Participants with confirmed histologically proven metastatic or locally advanced colorectal adenocarcinoma who are microsatellite stable (MSS) (ie, not microsatellite instable [MSI]) based on either an analysis of tissue from a prior biopsy or based on tissue from a new biopsy.
- •Participants with the presence of at least 1 lesion with measurable disease as defined by 10 millimeters (mm) in the longest diameter for a soft tissue lesions or 15 mm in the short axis for a lymph node by response evaluation criteria in solid tumors (RECIST) and immune related response-criteria (irRC) for a response assessment.
- •Participants has received at least 2 prior lines of standard chemotherapies for metastatic colorectal cancer (mCRC) and is refractory to or failing those chemotherapies.
- •Age greater than or equal to (>=) 18 years.
- •Eastern Cooperative Oncology Group performance status of 0 to 1
- •Life expectancy of >=4 months.
- •Has adequate organ function.
- •Women of childbearing potential must have a negative pregnancy test (urine or serum) within 7 days before starting study drugs. Is able to take medications orally.
- •Is able to take medications "orally".
排除标准
- •Has a serious illness or medical condition.
- •Treatment with any of the following within the specified time frame before enrollment:
- •Major surgery within the past 4 weeks (the surgical incision should be fully healed before study drug administration).
- •Any anticancer therapy within the past 3 weeks before enrollment.
- •Extended field radiation within the past 4 weeks or limited field radiation within the past 2 weeks before enrollment.
- •Any investigational drug/device received within the past 4 weeks or 5 times the half-life (whichever is shorter) before enrollment.
- •Previous treatment with TAS-
- •Prior treatment with anti-programmed cell death-1 (anti-PD-1), anti-programmed cell death ligand (anti-PD-L1), anti programmed cell death ligand 2, anti-CD137, anti-OX-40, anti CD40, anti cytotoxic T lymphocyte associated antigen-4 antibodies, or any other immune checkpoint inhibitors.
- •Unresolved toxicity of >=Common Terminology Criteria for Adverse Events version (CTCAE) version 4.03 grade 2 attributed to any prior therapies (excluding anemia, alopecia, skin pigmentation, and platinum induced neurotoxicity).
- •Prior events of immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune mediated nephritis and renal dysfunction, immune mediated rash, immune mediated encephalitis, and history of infusion reactions to nivolumab.
- •Known or assumed hypersensitivity to TAS-102 or nivolumab or any of its ingredients, including polysorbate 80-containing infusion.
- •Previous severe hypersensitivity reaction to treatment with another mAb.
- •Pregnant or lactating female.
- •Inappropriate for entry into this study in the judgment of the investigator.
研究组 & 干预措施
TAS-102 + Nivolumab
Participants received a dose of 35 milligrams per meter square (mg/m^2) of TAS-102 tablets orally twice per day (BID) within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 milligrams per kilogram per dose (mg/kg/dose) Nivolumab intravenous (I.V) infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle).
干预措施: TAS-102 (Drug)
TAS-102 + Nivolumab
Participants received a dose of 35 milligrams per meter square (mg/m^2) of TAS-102 tablets orally twice per day (BID) within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 milligrams per kilogram per dose (mg/kg/dose) Nivolumab intravenous (I.V) infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle).
干预措施: nivolumab (Drug)
结局指标
主要结局
Immune-Related Overall Response Rate (irORR)
时间窗: From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
irORR was defined as the percentage of participants achieving a complete response (irCR) or partial response (irPR) based on irRC criteria. Per irRC criteria, Complete Response (irCR) was defined as the disappearance of all tumor lesions (measurable or not, and no new lesions)., Partial Response (irPR) was defined as a decrease in the sum of the products of the two largest perpendicular diameters (SPD) by 50 percent (%) or greater by a consecutive assessment at least 4 weeks after first documentation, Stable Disease (irSD) was defined as the failure to meet criteria for irCR or irPR in absence of progressive disease (irPD), irPD was defined as at least 25% increase in SPD relative to nadir.
次要结局
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)(From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks))
- Number of Participants With Grade 3 or Higher Laboratory Tests Abnormalities(From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks))
- Overall Response Rate (ORR)(From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks))
- Progression-Free Survival (PFS) Based on Immune Related Response-Criteria (irRC)(From the first dose of study treatment to disease progression or death (up to 53 weeks))
- Recommended Phase 2 Dose (RP2D)(Cycle 1 (each cycle is of 4 weeks))
- Disease Control Rate (DCR) Based on irRC Criteria(From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks))
- Progression-Free Survival (PFS) Based on RECIST Criteria(From the first dose of study treatment to disease progression or death (up to 53 weeks))
- Number of Participants With Dose Limiting Toxicities (DLTs)(Cycle 1 (each cycle is of 4 weeks))
- Disease Control Rate (DCR) Based on RECIST Criteria(From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks))
- Overall Survival (OS)(From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks))