A Phase I Multicenter Study of Immunotherapy in Combination With Chemoradiation in Patients With Advanced Solid Tumors (CLOVER)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 105
- 试验地点
- 1
- 主要终点
- Number of subjects with Adverse Events (AEs)
研究概览
简要总结
This is an open-label, multicenter, phase I study to evaluate the safety and tolerability of durvalumab ± tremelimumab in combination with chemoradiation in patients with advanced solid tumors
详细描述
This study will initially treat up to approximately 300 patients with advanced solid tumors at approximately 30 sites, worldwide. The study will be composed of a dose-limiting toxicity (DLT) assessment phase (Part A) and an expansion phase (Part B).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 110 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
HNSCC Arm 1
Durvalumab + cisplatin with radiation in patients with locally advanced squamous cell carcinoma of the head and neck (HNSCC)
干预措施: Durvalumab (Drug)
HNSCC Arm 1
Durvalumab + cisplatin with radiation in patients with locally advanced squamous cell carcinoma of the head and neck (HNSCC)
干预措施: Cisplatin (dose level 4) (Drug)
HNSCC Arm 1
Durvalumab + cisplatin with radiation in patients with locally advanced squamous cell carcinoma of the head and neck (HNSCC)
干预措施: External beam radiation (dose level 1) (Radiation)
NSCLC Arm 1
Durvalumab + cisplatin and etoposide with radiation in patients with locally advanced, unresectable (Stage III) non-small-cell lung cancer (NSCLC)
干预措施: Durvalumab (Drug)
NSCLC Arm 1
Durvalumab + cisplatin and etoposide with radiation in patients with locally advanced, unresectable (Stage III) non-small-cell lung cancer (NSCLC)
干预措施: Etoposide (dose level 1) (Drug)
NSCLC Arm 1
Durvalumab + cisplatin and etoposide with radiation in patients with locally advanced, unresectable (Stage III) non-small-cell lung cancer (NSCLC)
干预措施: External beam radiation (dose level 2) (Radiation)
NSCLC Arm 1
Durvalumab + cisplatin and etoposide with radiation in patients with locally advanced, unresectable (Stage III) non-small-cell lung cancer (NSCLC)
干预措施: Cisplatin (dose level 1) (Drug)
NSCLC Arm 2
Durvalumab + carboplatin and paclitaxel with radiation in patients with locally advanced, unresectable (Stage III) non-small-cell lung cancer (NSCLC)
干预措施: Durvalumab (Drug)
NSCLC Arm 2
Durvalumab + carboplatin and paclitaxel with radiation in patients with locally advanced, unresectable (Stage III) non-small-cell lung cancer (NSCLC)
干预措施: Carboplatin (dose level 1) (Drug)
NSCLC Arm 2
Durvalumab + carboplatin and paclitaxel with radiation in patients with locally advanced, unresectable (Stage III) non-small-cell lung cancer (NSCLC)
干预措施: Paclitaxel (Drug)
NSCLC Arm 2
Durvalumab + carboplatin and paclitaxel with radiation in patients with locally advanced, unresectable (Stage III) non-small-cell lung cancer (NSCLC)
干预措施: External beam radiation (dose level 2) (Radiation)
NSCLC Arm 3
Investigator's choice of carboplatin and pemetrexed OR cisplatin and pemetrexed
干预措施: Durvalumab (Drug)
NSCLC Arm 3
Investigator's choice of carboplatin and pemetrexed OR cisplatin and pemetrexed
干预措施: Carboplatin (dose level 2) (Drug)
NSCLC Arm 3
Investigator's choice of carboplatin and pemetrexed OR cisplatin and pemetrexed
干预措施: Pemetrexed (Drug)
NSCLC Arm 3
Investigator's choice of carboplatin and pemetrexed OR cisplatin and pemetrexed
干预措施: External beam radiation (dose level 2) (Radiation)
NSCLC Arm 3
Investigator's choice of carboplatin and pemetrexed OR cisplatin and pemetrexed
干预措施: Cisplatin (dose level 2) (Drug)
SCLC Arm 1
Patients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin
干预措施: Durvalumab (Drug)
SCLC Arm 1
Patients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin
干预措施: Cisplatin (dose level 3) (Drug)
SCLC Arm 1
Patients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin
干预措施: Carboplatin (dose level 2) (Drug)
SCLC Arm 1
Patients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin
干预措施: Etoposide (dose level 2) (Drug)
SCLC Arm 1
Patients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin
干预措施: External beam radiation (standard) (Radiation)
SCLC Arm 2
Patients with limited-stage small-cell lung cancer (SCLC) should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin
干预措施: Durvalumab (Drug)
SCLC Arm 2
Patients with limited-stage small-cell lung cancer (SCLC) should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin
干预措施: Cisplatin (dose level 3) (Drug)
SCLC Arm 2
Patients with limited-stage small-cell lung cancer (SCLC) should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin
干预措施: Carboplatin (dose level 2) (Drug)
SCLC Arm 2
Patients with limited-stage small-cell lung cancer (SCLC) should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin
干预措施: Etoposide (dose level 2) (Drug)
SCLC Arm 2
Patients with limited-stage small-cell lung cancer (SCLC) should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin
干预措施: External beam radiation (hyperfractionated) (Radiation)
SCLC Arm 3
Patients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin. Note: Arm 3 will only be opened if the regimen in SCLC Arm 1 is safe and tolerable.
干预措施: Durvalumab (Drug)
SCLC Arm 3
Patients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin. Note: Arm 3 will only be opened if the regimen in SCLC Arm 1 is safe and tolerable.
干预措施: Tremelimumab (Drug)
SCLC Arm 3
Patients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin. Note: Arm 3 will only be opened if the regimen in SCLC Arm 1 is safe and tolerable.
干预措施: Cisplatin (dose level 3) (Drug)
SCLC Arm 3
Patients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin. Note: Arm 3 will only be opened if the regimen in SCLC Arm 1 is safe and tolerable.
干预措施: Carboplatin (dose level 2) (Drug)
SCLC Arm 3
Patients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin. Note: Arm 3 will only be opened if the regimen in SCLC Arm 1 is safe and tolerable.
干预措施: Etoposide (dose level 2) (Drug)
SCLC Arm 3
Patients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin. Note: Arm 3 will only be opened if the regimen in SCLC Arm 1 is safe and tolerable.
干预措施: External beam radiation (standard) (Radiation)
SCLC Arm 4
Patients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin Note: Arm 4 will only be opened if the regimen in SCLC Arm 2 is safe and tolerable.
干预措施: Durvalumab (Drug)
SCLC Arm 4
Patients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin Note: Arm 4 will only be opened if the regimen in SCLC Arm 2 is safe and tolerable.
干预措施: Tremelimumab (Drug)
SCLC Arm 4
Patients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin Note: Arm 4 will only be opened if the regimen in SCLC Arm 2 is safe and tolerable.
干预措施: Cisplatin (dose level 3) (Drug)
SCLC Arm 4
Patients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin Note: Arm 4 will only be opened if the regimen in SCLC Arm 2 is safe and tolerable.
干预措施: Carboplatin (dose level 2) (Drug)
SCLC Arm 4
Patients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin Note: Arm 4 will only be opened if the regimen in SCLC Arm 2 is safe and tolerable.
干预措施: Etoposide (dose level 2) (Drug)
SCLC Arm 4
Patients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin Note: Arm 4 will only be opened if the regimen in SCLC Arm 2 is safe and tolerable.
干预措施: External beam radiation (hyperfractionated) (Radiation)
结局指标
主要结局
Number of subjects with Adverse Events (AEs)
时间窗: From first dose of durvalumab up to 90 days after the last dose of study treatment
Number of subjects with Dose Limiting Toxicities (DLTs)
时间窗: From first dose of durvalumab until 28 days after completion of radiation therapy
次要结局
- Best objective response (BoR)(From first dose until disease progression, or the last evaluable assessment in the absence of progression, assessed up to 4 years.)
- Progression-free survival (PFS)(From first dose until the date of objective disease progression or death, in the absence of progression at 12, 18 and 24 months, up to 4 years.)
- Duration of response (DoR)(From first dose until disease progression, or death, in the absence of progression, assessed up to 4 years.)
- Overall Survival (OS)(From first dose until death due to any cause through study completion, up to 4 years)
- Objective response rate (ORR)(From first dose until disease progression, or the last evaluable assessment in the absence of progression, assessed up to 4 years.)
- Disease control rate (DCR)(From first dose until disease progression, at 18 weeks and 48 weeks.)
- Disease-free survival (DFS)(From first dose until disease progression or death, in the absence of progression at 12, 18 and 24 months, assessed up to 4 years.)