Nal-IRI/LV5-FU VERSUS PACLITAXEL AS SECOND-LINE THERAPY IN PATIENTS WITH METASTATIC OESOPHAGEAL SQUAMOUS CELL CARCINOMA A Multi-centre, Randomized, Non-comparative Phase II Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 106
- 试验地点
- 9
- 主要终点
- survival at 9 months
研究概览
简要总结
The aim of our study is to evaluate the efficacy and safety of NALIRI plus 5FU versus paclitaxel as a second-line therapy in patients with locally advanced or metastatic ESCC who had failed to cisplatin- or oxaliplatin-based first-line chemotherapy.
The hypotheses are as follows:
H0: the percentage of patients alive at 9 months of 40% is not useful. H1: the percentage of patients alive at 9 months of 60% is expected.
详细描述
Principal objective:
• To evaluate the survival of patients at 9 months
Secondary objectives:
- Progression-free survival (PFS) (clinical and/or radiological)
- Overall survival (OS)
- Best response rate during treatment according to RECIST 1.1 criteria (according to the investigator and the centralised review committee)
- Toxicity (NCI CTC 4.0)
- Quality of life (QLQ-C30 and OES18 questionnaires of the EORTC)
Arm A (experimental arm): Nal IRI plus LV5-FU (D1=D28) Nal-IRI: 70 mg/m² intravenous over 90 minutes Followed by intravenous folinic acid 400 mg/m² over 30 minutes or L-folinic acid: 200 mg/m² over 30 minutes And then 5-FU 2,400 mg/m² over 46 hours on D1 to D14
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically proven metastatic oesophageal squamous cell carcinoma
- •Patient in failure with 1st-line treatment with oxaliplatin or cisplatin. Patients presenting with resectable disease treated with surgery or neoadjuvant or adjuvant chemotherapy with oxaliplatin or cisplatin (with or without radiotherapy) can be included if a recurrence has occurred less than 6 months after the end of treatment
- •Age ≥ 18 years
- •Unresectable disease, measurable or not, according to RECIST 1.1 criteria
- •WHO performance status ≤ 2
- •Neutrophils ≥ 1500/mm3 (without use of haematopoietic growth factors), platelets ≥ 100 000/mm3, haemoglobin ≥ 9 g/dl (blood transfusions are authorised for patients with a haemoglobin less than 9 g/dl)
- •Total bilirubin ≤ 2 x ULN (biliary drainage is authorised in case of a biliary obstruction); albumin ≥ 25 g/L; AST ≤ 2.5 x ULN, and ALT ≤ 2.5 x ULN (≤ 5 x ULN in case of hepatic metastases)
- •Creatinine clearance ≥ 50 ml/min according to MDRD formula
- •A normal ECG or ECG with no clinically significant findings
- •Patient able to understand and to sign the informed consent form (or who has a legal guardian able to do so for him/him)
- •Women of childbearing potential must have a negative pregnancy blood or urine test within 7 days prior to inclusion
- •Women of childbearing potential, as well as men (who have sexual relations with women of childbearing potential) must agree to use an effective method of contraception throughout this study and during the 6 months following administration of the last dose of the study medicinal product
- •Patient who is a beneficiary of the Social security system
- •Patient for whom regular follow-up is possible.
排除标准
- •Known brain or bone metastases
- •Clinically significant gastrointestinal disorders, including hepatic, haemorrhagic, inflammatory, obstructive disorders or diarrhoea > grade 1
- •History of chronic inflammatory bowel disease
- •Gilbert's syndrome
- •Interstitial lung disease
- •Treatment with St John's Wort
- •Medical history of Whipple procedure
- •Body mass index < 18.5 kg/m2
- •Combination with sorivudine and others analogues as brivudine (irreversibly inhibits the enzyme dihydropyrimidine dehydrogenase)
- •History of progressive cancer or in remission of less than 3 years duration (patients who present with a cancer in situ or basal cell or squamous cell skin cancer during the last 3 years are eligible).
- •Severe arterial thromboembolic events (myocardial infarction, unstable angina, stroke) less than 3 months before inclusion
- •NYHA class III or IV congestive heart failure, ventricular arrhythmia or uncontrolled blood pressure
- •Significant neuropathy ≥ grade 2 according to NCI CTCAE criteria (National Cancer Institute Common Terminology Criteria for Adverse Events) v.4.
- •Known hypersensitivity or allergy to a component of the medicinal products used in the study.
- •Known DPD deficiency
研究组 & 干预措施
arm A: ONIVYDE
ONIVYDE ONIVYDE will be administered first, followed by folinic acid or L-folinic acid and then 5-FU at D1 and D14 ONIVYDE: 70 mg/m² intravenous over 90 minutes Folinic acid: 400 mg/m² intravenous over 30 minutes or L-folinic acid (racemic form L) 200 mg/m² over 30 minutes 5-FU: 2400 mg/m² over 46 hours
干预措施: Onivyde (Drug)
Arm B: TAXOL
TAXOL Premedication consists of corticosteroids, H1 antihistamines and H2 antagonists during 30 minutes at time 1 hour before chemotherapy One cycle every 28 days (D1=D28) 80 mg/m2 IV over 60 minutes at D1, D8 and D15
干预措施: Paclitaxel (Drug)
结局指标
主要结局
survival at 9 months
时间窗: 9 months
The principal objective is to evaluate survival at 9 months in patients presenting with metastatic oesophageal squamous cell carcinoma (OSC) treated with Nal-IRI/LV5-FU or with paclitaxel.
次要结局
- Progression-free survival(5 years)
- Overall survival (OS)(1 year)
- Best response rate during treatment(6 months)
- Toxicity (NCI-CTC v4)(6 months)
- Quality of life (questionnaires)(6 months)