Durvalumab (MEDI4736) as Maintenance Treatment Following Chemoradiation for Locally Advanced Unresectable Esophageal Squamous Cell Carcinoma (DESC).
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Six-month progression-free survival
研究概览
简要总结
Single arm phase II trial designed to assess the efficacy of durvalumab treatment in terms of 6-month progression-free survival. We will include 22 patients who will receive 1500 mg durvalumab (MEDI4736) via IV infusion Q4W <<for up to a maximum of 12 months (up to 13 doses/cycles) with the last administration on week 48>> or <<until confirmed disease progression>> unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met. If a patient's weight falls to 30 kg or below for 1 week or longer ( ≥ 7 days) durvalumab will be permanently discontinued.
详细描述
A) Study Title: Durvalumab (MEDI4736) as maintenance treatment following chemoradiation for locally advanced unresectable esophageal squamous cell carcinoma (DESC)
B) Protocol Number: ESR-17-12757
C) Clinical Phase: 2
D) Study Duration: 36 months
E) Investigational Product(s) and Reference Therapy: Durvalumab (MEDI4736)
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
- •Body weight >30kg and body mass index ≥ 16 kg / m2;
- •Patients aphagic or able to ingest only liquids should also receive enteral nutritional sup-port before being included in the study;
- •Patients must have histologically confirmed esophageal or esophagogastric junction (Siewert I or II) squamous cell carcinoma, irrespective of PD-1/PD-L1 or other biomarkers expression;
- •Patients must have had a persistent disease 6-8 weeks after completing chemoradiotherapy with at least 50 Gy and platinum-based chemo and without complete response or progressive disease, based on upper endoscopy and/or CT scans;
- •Patients must have realized CT scans within 6-8 weeks after completion of chemoradiotherapy, revealing persistent disease;
- •Patients must be included <12 weeks after completing chemoradiotherapy;
- •Patients must be unsuitable to salvage esophagectomy, according multidisciplinary local board;
- •All the tumor volume should have been treated with CRT (included in the radiation field);
- •Eastern Cooperative Oncology Group (ECOG)>><<World Health Organisation (WHO) performance status of 0 or 1;
- •Male or female aged 18 years or older at time of study entry;
- •Life expectancy of > 12 weeks;
- •Adequate normal organ and marrow function as defined below:
- •Haemoglobin ≥9.0 g/dL
- •Absolute neutrophil count (ANC) 1.5 x (> 1500 per mm3)
- •Platelet count ≥100 x 109/L
- •Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). <<This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
- •AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN
- •Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance: CrCl, mL/min = (140 - age) × (weight, kg) × (0.85 if female) / (72 × Cr)
- •All toxicities attributed to prior chemoradiotherapy other than alopecia, fatigue, or peripheral neuropathy must have resolved to grade 2 or less;
排除标准
- •Patients with metastases including lymph node not included in the radiation field;
- •Patients currently receiving or have had prior use of immunosuppressive medication within 28 days before the first dose of study drug (10 milligrams/day of prednisone or an equivalent corticosteroid is allowed);
- •Received any immunotherapy for esophageal cancer;
- •Patients with active hepatitis B, hepatitis C or human immunodeficiency virus (HIV1/2 antibodies);
- •Has known active or prior autoimmune disease, except for:
- •skin diseases (vitiligo, psoriasis, alopecia)
- •diabetes mellitus type 1, with hormone replacement
- •hypothyroidism, with hormone replacement
- •Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.
- •Grade 3 or higher pulmonary toxicity of dyspnea, hypoxia, or pneumonitis experienced during chemoradiation;
- •Presence of fistula between esophagus and trachea unless treated with endoscopic prosthesis.
研究组 & 干预措施
Durvalumab
1500 mg durvalumab (MEDI4736) via IV infusion Q4W <<for up to a maximum of 12 months (up to 13 doses/cycles) with the last administration on week 48>> or <<until confirmed disease progression>> unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met.
干预措施: Durvalumab (Drug)
结局指标
主要结局
Six-month progression-free survival
时间窗: 6 months
The primary endpoint is the percentage of subjects who remain progression free at 6 months using investigator assessments according to RECIST 1.1
次要结局
- Incidence of Treatment-Related Adverse Events [Safety and Tolerability](From time of informed consent through treatment period (12 months) or up to 12 months post last dose of study treatment.)
- Overall survival(From time of informed consent until the date of death from any cause, assessed up to 60 months)
- Incidence of locoregional progression(From time of informed consent through treatment period (12 months) or up to 12 months post last dose of study treatment.)
- Incidence of distant progression(From time of informed consent through treatment period (12 months) or up to 12 months post last dose of study treatment.)
研究者
Tiago Biachi
Principal Investigator
Instituto do Cancer do Estado de São Paulo