NCT03722108终止1 期
A Randomised Phase 2 Trial Assessing REGorafenib Combined With IRInotecan as Second-line Treatment in Patients With Metastatic Gastro-oesophageal Adenocarcinomas
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- UNICANCER
- 入组人数
- 89
- 试验地点
- 27
- 主要终点
- To compare the efficacy of regorafenib combined with irinotecan versus irinotecan alone in terms of overall survival (OS)
研究概览
简要总结
Trial evaluating the efficacy of regorafenib combined with irinotecan compared to irinotecan alone in second-line treatment of patients with metastatic gastro-oesophageal adenocarcinomas.
详细描述
Comparative interventional prospective phase 2, randomised, open-label, multicentric trial comparing the combination of regorafenib and irinotecan (REGIRI) to irinotecan alone (IRI) as second line treatment of patients with metastatic gastro-oesophageal adenocarcinomas.
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
- •Patient must have signed a written informed consent form prior to any study specific procedures
- •Patients aged ≥18 years old
- •Histologically confirmed diagnosis of gastro-oesophageal adenocarcinomas: gastroesophageal junction (Siewert II and III) and gastric adenocarcinomas
- •Asymptomatic primary tumour
- •Metastatic disease
- •At least one target lesion (according to RECIST v1.1):
- •Unidimensionally measurable on cross-sectional imaging
- •In an area not previously irradiated
- •Disease progression after a fluoropyrimidine and platinum agent-based chemotherapy (5-fluorouracil or 5-fluorouracil prodrugs combined with cisplatin or oxaliplatin). For example, docetaxel combined with FOLFOX, PD-L1/PD-1 inhibitors combined with FOLFOX, LV5-FU2-cisplatin or 5-fluorouracil-cisplatin are acceptable prior therapies.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤1
- •Life expectancy >3 months
- •Amylase ≤1.5 x upper limit of normal (ULN) and lipase ≤1.5 x ULN
- •Adequate liver function:
- •Total bilirubin ≤1.5 x ULN
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 x ULN (≤5 x ULN for patients with liver metastasis)
- •Alkaline phosphatase (ALP) ≤2.5 x ULN (≤5.0 x ULN for patients with liver or bone metastases)
- •Platelet count ≥100,000/mm³; haemoglobin (Hb) ≥9 g/dL; absolute neutrophil count (ANC) ≥1,500/mm³. The use of blood transfusion(s) to meet the inclusion criteria will not be allowed
- •International normalised ratio (INR) ≤1.5 x ULN and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤1.5 x ULN unless receiving treatment with therapeutic anticoagulation. Patients being treated with anticoagulant, e.g., heparin, are eligible if there is no evidence of an underlying abnormality with these parameters and if a close monitoring of at least weekly evaluations was performed until INR and PTT are stable based on a pre-dose measurement as defined by the local standard of care
- •Creatinine clearance (CLcr) ≥50 mL/min estimated by Cockcroft-Gault equation
- •Women of childbearing potential and men must agree to use adequate contraception during the study and for at least 3 months after the last study drug administration
- •Patients affiliated to the social security system
排除标准
- •Symptomatic brain metastases or carcinomatous meningitis
- •Bone-only metastasis
- •Known and documented UGT1A1 deficiency
- •History of Gilbert's syndrome
- •Previous or concurrent cancer with a distinct primary site, other than gastro-oesophageal cancer, within 5 years prior to randomisation (except for curatively treated cervical cancer in situ, non-melanoma skin cancer, and superficial bladder tumours)
- •Persistent proteinuria >3.5 g/24 h measured by urine protein-creatinine ratio from a random urine sample (grade ≥3, NCI-CTCAE v 5.0)
- •Interstitial lung disease with ongoing signs and symptoms at inclusion
- •Known hypersensitivity to any of the study drugs, study drug classes, or excipients
- •Non-healing wound, non-healing ulcer, or non-healing bone fracture
- •Patients with evidence or history of any bleeding diathesis, irrespective of severity
- •Any haemorrhage or bleeding event grade ≥3 (NCI-CTCAE v.5.0) within 4 weeks before starting of the study treatment
- •Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 month before starting the study treatment (except for adequately treated catheter-related venous thrombosis occurring more than one month before the start of study medication)
- •Previous major surgical procedure, significant traumatic injury, or radiotherapy within the 4 weeks before inclusion
- •Uncontrolled hypertension (systolic blood pressure >140 mmHg or diastolic pressure >90 mmHg) despite optimal medical management. Congestive heart failure: New York Heart Association (NYHA) ≥ class 2
- •Unstable angina (angina symptoms at rest), new-onset angina (that started within the last 3 months)
- •Myocardial infarction less than 6 months before starting the study treatment
- •Uncontrolled cardiac arrhythmias
- •History of epileptic seizures requiring long-term anticonvulsant therapy
- •History of organ transplantation with use of immunosuppression therapy
- •Ongoing bacterial or fungal infection (grade >2 by NCI-CTCAE v.5.0)
- •Known history of human immunodeficiency virus (HIV) infection
- •Active hepatitis B or C, or chronic hepatitis B or C requiring treatment with antiviral therapy
- •Use of CYP3A4 inducers or inhibitors
- •Pregnant or breast-feeding women
- •Bowel malabsorption or extended bowel resection that could affect the absorption of regorafenib, occlusive syndrome, inability to take oral medications
- •Inflammatory bowel disease with chronic diarrhoea
- •Participation in another clinical trial within the 30 days before inclusion
- •Concurrent treatment with another investigational product or anticancer therapy (other than irinotecan or regorafenib)
- •Concomitant treatment with hypericum or live attenuated vaccines
- •Gastro-intestinal fistula or perforation
- •Person kept in detention or incapable of giving consent
- •Patient unwilling or unable to comply with the medical follow-up required by the study because of geographic, social, or psychological reasons
研究组 & 干预措施
Regorafenib and Irinotecan
Experimental
Irinotecan 180 mg/m² on Day1 and Day 15 of a 4 week cycle combined with regorafenib 160 mg daily on Day2-8 and D16-22 of a 4 week cycle administered until progression of disease or unacceptable toxicity.
干预措施: Regorafenib and Irinotecan (Combination Product)
Irinotecan
Active Comparator
Irinotecan 180 mg/m² on Day1 and Day 15 of a 4 week cycle administered until progression of disease or unacceptable toxicity
干预措施: Irinotecan (Drug)
结局指标
主要结局
To compare the efficacy of regorafenib combined with irinotecan versus irinotecan alone in terms of overall survival (OS)
时间窗: expected duration of 10 months from randomisation
Time duration from randomisation to time of death of any cause. If a patient is alive at the database cut-off date, then the patient will be censored at the last date of follow-up.
次要结局
- To compare the efficacy of regorafenib combined with irinotecan versus irinotecan alone in terms of the overall survival rate(6 and 12 months from randomisation)
- To compare the efficacy of regorafenib combined with irinotecan versus irinotecan alone in terms of the progression-free survival (PFS)(expected duration of 6 months from randomisation)
- To evaluate the efficacy of regorafenib combined with irinotecan versus irinotecan alone in terms of the progression-free survival rate(6 and 12 months from randomisation)
- To evaluate the efficacy of regorafenib combined with irinotecan versus irinotecan alone in terms of the disease control rate (DCR)(expected duration of 6 months from randomisation)
- To evaluate the efficacy of regorafenib combined with irinotecan versus irinotecan alone in terms of the objective response rate (ORR)(expected duration of 6 months from randomisation)
- To compare treatment-related toxicity(expected 30 days after last study treatment administration)
- To compare the effect of treatment on quality of life(expected 30 days after last study treatment administration)
- To compare the effect of treatment on quality of life related to gastro-oesophageal cancer(expected 30 days after last study treatment administration)
研究者
研究点 (27)
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