A Phase III Randomized, Open-label, Multi-center, Global Study of MEDI4736 Alone or in Combination With Tremelimumab Versus Standard of Care in the Treatment of First-line Recurrent or Metastatic Squamous Cell Head and Neck Cancer Patients
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 823
- 试验地点
- 1
- 主要终点
- Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab Versus Standard of Care (SOC)
研究概览
简要总结
This is a randomized, open-label, multi-center, 3-arm, global Phase III study to determine the efficacy and safety of MEDI4736 + tremelimumab combination or MEDI4736 monotherapy versus SoC (EXTREME regimen) in the treatment of patients with SCCHN who have not received prior systemic chemotherapy for recurrent or metastatic disease.
详细描述
Patients will be randomized in a 2:1:1 ratio to MEDI4736 + tremelimumab combination therapy, MEDI4736 monotherapy, or SoC. Patients in all arms will continue therapy until progression. Tumor assessments will be performed on computed tomography scans or magnetic resonance imaging scans, preferably with intravenous (IV) contrast. Efficacy for all patients will be assessed by objective tumor assessments every 6 weeks for the first 24 weeks, then every 8 weeks thereafter until treatment discontinuation due to progression or toxicity. All patients will be followed every 3 months for survival after progression is confirmed.
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 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years at the time of screening
- •Documented evidence of recurrent or metastatic SCCHN (oral cavity, oropharynx, hypopharynx, or larynx).
- •A fresh tumor biopsy for the purpose of screening or an available archival tumor sample. Tumor lesions used for fresh biopsies should not be the same lesions used as RECIST target lesions, unless there are no other lesions suitable for biopsy.
- •No prior systemic chemotherapy for recurrent or metastatic disease
- •World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment
- •No prior exposure to immune-mediated therapy,
排除标准
- •Histologically or cytologically confirmed head and neck cancer of any other primary anatomic location in the head and neck not specified in the inclusion criteria including patients with SCCHN of unknown primary or non-squamous histologies (eg, nasopharynx or salivary gland)
- •Tumor progression or recurrence within 6 months of last dose of platinum therapy in the primary treatment setting
- •Receipt of any radiotherapy or hormonal therapy for cancer treatment within 30 days prior to first dose of study treatment
- •Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis, Crohn's disease], diverticulitis
研究组 & 干预措施
Monotherapy
MEDI4736 monotherapy.
干预措施: MEDI4736 (Biological)
Combination Therapy
MEDI4736+Tremelimumab combination therapy
干预措施: Tremelimumab (Biological)
Combination Therapy
MEDI4736+Tremelimumab combination therapy
干预措施: MEDI4736+Tremelimumab (Biological)
Standard of Care
Standard of Care treatment
干预措施: Cetuximab (Biological)
Standard of Care
Standard of Care treatment
干预措施: 5-fluorouracil (5FU) (Drug)
Standard of Care
Standard of Care treatment
干预措施: Cisplatin (Drug)
Standard of Care
Standard of Care treatment
干预措施: Carboplatin (Drug)
结局指标
主要结局
Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab Versus Standard of Care (SOC)
时间窗: From date of randomization until time of final analysis, an average of approximately 4 years
Number of participants with Overall Survival (OS)
Overall Survival (OS) Median Duration in the PD-L1 TC/IC High Subgroup
时间窗: From date of randomization until time of final analysis, an average of approximately 4 years
Time from the date of randomization until death due to any cause (i.e., date of death or censoring - date of randomization + 1)
次要结局
- Overall Survival (OS) Median Duration in the All-comers (Full Analysis Set)(From date of randomization until time of final analysis, an average of approximately 4 years)
- Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab + Tremelimumab Versus Standard of Care (SOC)(From date of randomization until time of final analysis, an average of approximately 4 years)
- Percentage of Patients Alive at 12, 18 and 24 Months in the PD-L1 TC/IC High Subgroup(12, 18 and 24 months after randomization)
- Progression Free Survival (PFS) in the All-comers (Full Analysis Set)(Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years)
- Overall Survival (OS) Status in the All-comers (Full Analysis Set)(From date of randomization until time of final analysis, an average of approximately 4 years)
- Percentage of Patients Alive at 12, 18 and 24 Months in the All-comers (Full Analysis Set)(12, 18 and 24 months after randomization)
- Objective Response Rate (ORR) in the All-comers (Full Analysis Set)(Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years)
- Duration of Response (DoR) in the PD-L1 TC/IC High Subgroup(Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years)
- Progression Free Survival (PFS) in the PD-L1 TC/IC High Subgroup(Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years)
- Objective Response Rate (ORR) in the PD-L1 TC/IC High Subgroup(Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years)
- Duration of Response (DoR) in the All-comers (Full Analysis Set)(Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years)