PDL-1 Targeting in Resectable Oesophageal Cancer: a Phase II Feasibility Study of Atezolizumab and Chemoradiation.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- feasibility defined as percentage completion of treatment with atezolizumab.
研究概览
简要总结
Objectives The primary objective of this study is to assess the feasibility of preoperative treatment with atezolizumab combined with preoperative chemoradiation (carboplatin, paclitaxel and radiation) in terms of completion of treatment with atezolizumab.
详细描述
Objectives The primary objective of the study of this study is to assess the feasibility of preoperative treatment with atezolizumab combined with preoperative chemoradiation (carboplatin, paclitaxel and radiation) in terms of completion of treatment with atezolizumab.
Secondary objectives are:
- To assess toxicities of atezolizumab alone and in combination with chemoradiation.
- To assess completion of chemotherapy and radiation treatment
- To assess withdrawal rate from surgery
- To assess post-operative complications.
- To assess pathological response.
- To assess R0 resection rate.
- To assess the relation between gut microbiota composition and response.
- To assess the relation between gut microbiota composition and toxicity.
Explorative objectives are:
To perform exploratory biomarker analyses from tumor tissue and blood-derived samples and correlate with safety and clinical outcome. Biomarker analyses include (but are not limited to):
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
- •Histologically proven adenocarcinoma of the esophagus or gastro esophageal junction.
- •Surgical resectable (<T4b, N0 or N+, M0), as determined by Endoscopic Ultra Sound (EUS) and CT scan of neck, thorax and abdomen. Tumors that cannot be passed with an endoscope for endoscopic ultrasound are eligible if all other criteria are fulfilled.
- •T1N+ tumors are eligible.
- •Tumor length longitudinal ≤ 10 cm; if larger than 10 cm, inclusion should be discussed with the principal investigator.
- •If the tumor extends below the gastroesophageal (GE) junction into the proximal stomach, the bulk of the tumor must involve the esophagus or GE junction.
- •ECOG performance status 0 or 1 (cf. Appendix A).
- •Adequate hematological, renal and hepatic functions defined as:
- •neutrophiles ≥ 1.5 x 109/L
- •platelets ≥ 100 x 109/L
- •hemoglobin ≥ 5.6 mmol
- •total bilirubin ≤ 1.5 x upper normal limit
- •creatinine clearance (Cockroft) > 60 ml/min
- •Written, voluntary informed consent
- •Patients must be accessible to follow up and management in the treatment center
排除标准
- •Past or current history of malignancy other than entry diagnosis interfering with prognosis of esophageal cancer.
- •Invasion of the tracheobronchial tree or presence of tracheoesophageal fistula.
- •T1N0 tumors or in situ carcinoma.
- •Pregnancy (positive serum pregnancy test), planning to become pregnant, and lactation.
- •Patient (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment.
- •Previous chemotherapy, radiotherapy, and/or treatment with checkpoint inhibitors.
- •Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) precluding major surgery.
- •Pulmonary fibrosis and/or severely impaired lung function precluding major surgery.
- •Pre-existing motor or sensory neurotoxicity greater than WHO grade
- •Serious underlying medical condition which would impair the ability of the patient to receive the planned treatment, including prior allergic reactions to drugs containing Cremophor, such as teniposide or cyclosporine.
- •Dementia or altered mental status that would prohibit the understanding and giving of informed consent
- •Inadequate caloric- and/or fluid intake despite consultation of a dietician and/or tube feeding.
- •Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine for patients with a history of autoimmune-related hypothyroidism, insulin for patients with type 1 diabetes mellitus, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Patients with vitiligo with dermatological manifestations only are eligible to enter the study.
- •Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (>10 mg/day prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- •Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
- •Has an active infection requiring systemic therapy which has not resolved 3 days (simple infection such as cystitis) to 7 days (severe infection such as pyelonephritis) prior to the first dose of trial treatment.
- •Patients with prior allogeneic stem cell or solid organ transplantation.
研究组 & 干预措施
Atezolizumab and Chemoradiation
Atezolizumab 1200 mg i.v. day 1-22-43-64-85 Carboplatin AUC = 2 i.v day 1-8-15-22-29 Paclitaxel 50 mg/m2 i.v day 1-8-15-22-29 Radiotherapy 23 x 1.8 Gy
干预措施: Atezolizumab (Drug)
Atezolizumab and Chemoradiation
Atezolizumab 1200 mg i.v. day 1-22-43-64-85 Carboplatin AUC = 2 i.v day 1-8-15-22-29 Paclitaxel 50 mg/m2 i.v day 1-8-15-22-29 Radiotherapy 23 x 1.8 Gy
干预措施: Carboplatin (Drug)
Atezolizumab and Chemoradiation
Atezolizumab 1200 mg i.v. day 1-22-43-64-85 Carboplatin AUC = 2 i.v day 1-8-15-22-29 Paclitaxel 50 mg/m2 i.v day 1-8-15-22-29 Radiotherapy 23 x 1.8 Gy
干预措施: Paclitaxel (Drug)
Atezolizumab and Chemoradiation
Atezolizumab 1200 mg i.v. day 1-22-43-64-85 Carboplatin AUC = 2 i.v day 1-8-15-22-29 Paclitaxel 50 mg/m2 i.v day 1-8-15-22-29 Radiotherapy 23 x 1.8 Gy
干预措施: Radiotherapy 23 x 1.8 Gy (Radiation)
结局指标
主要结局
feasibility defined as percentage completion of treatment with atezolizumab.
时间窗: up to 3 months
The primary endpoint is feasibility defined as percentage completion of treatment with atezolizumab
次要结局
- Overall survival(up to 3 months)
- Percentage withdrawal rate from surgery due to atezolizumab related complications(up to 3 months)
- Incidence and severity of toxicity(up to 3 months)
- Percentage completion of chemotherapy and radiation treatment(up to 3 months)
- Percentage delay of surgery due to atezolizumab related complications(up to 3 months)
- Incidence and severity of post-operative complications to the Dindo classification(up to 3 months)
- Pathological response according to the Mandard criteria(up to 3 months)
- R0 resection rate.(up to 3 months)
- Progression free survival(up to 3 months)
研究者
H.W.M. van Laarhoven
Prof. dr.
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)