Stereotactic Radiotherapy + Anti PD-1 Therapy in Patients With Locally Advanced Unresectable Pancreatic Adenocarcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 4
- 主要终点
- Safety - incidence of treatment-related adverse events
研究概览
简要总结
Stereotactic Radiotherapy + Anti PD-1 Therapy in Patients With Locally Advanced Unresectable Pancreatic Adenocarcinoma
详细描述
Phase I/II, multicentre, open label, with no control arm clinical trial of 4-weeks stereotactic radiotherapy followed by nivolumab 3 mg/kg every two weeks in adults with locally advanced pancreatic cancer who does not progress during 4 cycles of standard chemotherapy FOLFIRINOX
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
- •Male and female patients aged ≥18 years
- •Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1
- •Locally advanced, unresectable, histologically confirmed primary adenocarcinoma of pancreas with no progression during induction chemotherapy (4 cycles of FOLFIRINOX - not a part of trial). Within screening period tumor tissue must be available and sent to the central pathological reviewer in order to confirm the diagnosis.
- •Measurable (one target lesion is sufficient) disease as per RECIST 1.1 criteria
- •Laboratory values:
- •Aspartate aminotransferase (AST) ≤ 3x ULN (upper limit of normal)
- •Alanine transaminase (ALT) ≤ 3x ULN
- •Total bilirubin ≤ 1.5 x ULN (except subjects with Gilbert syndrome who must have a total bilirubin ≤ 3x ULN)
- •Creatinine: Serum creatinine ≤ 1.5 ULN or creatinine clearance > 50ml/min (using Cockcroft/Gault formula)
- •White blood cells ≥ 2000 /ul
- •Neutrophils ≥ 1500 /ul
- •Platelets ≥ 100x 103 /ul
- •Hemoglobin ≥ 9.0 g/l
- •Women of childbearing potential (WOCBP) must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study treatment. WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) and who is not postmenopausal. Menopause is defined as 12 months of amenorrhea in a woman over age 45 years in the absence of other biological or physiological causes. In addition, females under age of 55 years must have serum follicle stimulating hormone (FSH) level > 40mIU/ml to confirm menopause.
排除标准
- •Other histology then primary pancreatic adenocarcinoma
- •Resectable disease
- •Distant metastases
- •Progressive disease during induction chemotherapy (4 cycles of FOLFIRINOX)
- •Other previous treatment of the disease except induction chemotherapy (4 cycles of FOLFIRINOX)
- •ECOG performance score of 2 or more
- •Previous therapy of malignant disease in 5 years and less before inclusion to the trial (except skin epithelial tumors)
- •Previous radiotherapy in abdominal region
- •Previous immunological treatment (anti-CTLA-4, anti-PD1 or anti-PD-L1)
- •Active, known or suspected serious autoimmune disease
- •Major surgery less than 28 days prior to the first dose of study treatment
- •Treatment of any investigational medicinal product within 4 weeks before this trial enrolment
- •Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
- •Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency synrome (AIDS)
- •Prisoners or subjects who are involuntarily incarcerated
- •Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness
研究组 & 干预措施
Arm 1
4-weeks stereotactic radiotherapy followed by nivolumab 3 mg/kg every two weeks
干预措施: Nivolumab (Drug)
Arm 1
4-weeks stereotactic radiotherapy followed by nivolumab 3 mg/kg every two weeks
干预措施: Stereotactic radiotherapy (Radiation)
结局指标
主要结局
Safety - incidence of treatment-related adverse events
时间窗: Through study completion, an average of 4 years
Measured by the incidence of adverse events (AEs), serious adverse events (SAEs), deaths
Safety - incidence of laboratory abnormalities
时间窗: Through study completion, an average of 4 years
Biochemistry - Na (mmol/l), K (mmol/l), Cl (mmol/l), Ca (mmol/l), Ca ionized (mmol/l), Mg (mmol/l), P (mmol/l), urea (mmol/l), creatinine (µmol/l), LDH (µkat/l), AST(µkat/l), ALT(µkat/l), ALP(µkat/l), GMT(µkat/l), total bilirubin (µmol/l), conjuged bilirubin (µmol/l), total protein (g/l), albumin (g/l), fasting glucose (mmol/l), amylase (µkat/l), C-reactive protein (mg/l), endocrine panel - TSH (mU/l), Free T3 (pmol/l), Free T4 (pmol/l), hematology - complete blood count (CBC): hemoglobin (g/l), hematocrit (ratio), white blood cells (WBC) (10E9/l), red blood cells (10E12/l), platelets (10E9/l) including differential (all 10E9/l), coagulation - APTT (ratio), PT (ratio)
次要结局
- Progression free survival(Through study completion, an average of 4 years)
- Relationship of laboratory markers and progression(Through study completion, an average of 4 years)
- patient's capacity to fulfill the activities of daily living and quality of life(Through study completion, an average of 4 years)
- Overall survival(Through study completion, an average of 4 years)