Randomized Phase II Trial of Fluorouracil and Folinic Acid With or Without Liposomal Irinotecan (ONIVYDE) for Patients With Metastatic Biliary Tract Cancer Which Progressed Following Gemcitabine Plus Cisplatin
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 178
- 试验地点
- 1
- 主要终点
- Progression Free Survival by independent central reviewer
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of combination of fluorouracil/folinic acid and liposomal irinotecan(Onivyde) compared with fluoruracil/folinic acid in patients with metastatic biliary tract cancer which progressed on 1st line gemcitabine/cisplatin.
详细描述
This study is a multicenter, open-label, randomized, phase II study comparing the efficacy and safety between fluorouracil/folinic acid plus liposomal irinotecan and fluoruracil/folinic acid monotherapy in patients with metastatic biliary tract cancer which progressed on 1st line gemcitabine/cisplatin.
Eligible patients will be included in this study and treated according to the protocol. Study treatment will be continued until disease progression, unacceptable toxicity, or patient's decision/consent withdrawal. Local investigators will determine disease progression, radiologic or clinical deterioration.
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
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed and written informed consent form
- •≥ 19 years of age
- •Histologically or cytologically confirmed cholangiocarcinoma
- •Documented metastatic disease
- •At least one measurable lesion according to the RECIST v1.1
- •Disease progression on gemcitabine-cisplatin combination therapy
- •For patients whose disease recurred after curative resection (R0 or R1), previous adjuvant 5-FU-based chemotherapy is allowed if there is at least 6 month-interval between the last dose of adjuvant chemotherapy and recurrence of disease.
- •Adequate hepatic, renal and hematological function AST(Aspartate Aminotransferase), ALT(Alanine Aminotransferase) ≤ 100 IU/L (100 U/L), Cr(Creatinine) ≤ 1.5mg/dL
- •Eastern Cooperative Oncology Group (ECOG) Performance status 0-1
排除标准
- •Serum total bilirubin ≥2 x ULN(upper limit of normal) (biliary drainage is allowed for biliary obstruction)
- •Severe renal impairment (Clcr ≤ 30 ml/min)
- •Inadequate bone marrow reserves as evidenced by:
- •ANC(Absolute Neutrophile Count) ≤ 1,500 cells/μl; or
- •Platelet count ≤ 100,000 cells/μl; or
- •Hemoglobin ≤ 9 g/dL
- •ECOG performance status 2-4
- •Any clinically significant disorder impacting the risk-benefit balance negatively per physician's judgment
- •Any clinically significant gastrointestinal disorder, including hepatic disorders, bleeding, inflammation, occlusion, or diarrhea > grade 2
- •Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) in last 6 months
- •NYHA(New York Heart Association) Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure. Or known abnormal ECG with clinically significant abnormal findings
- •Active infection or an unexplained fever >38.5°C (excluding tumor fever), which in the physician's opinion might compromise the patient's health
- •Current use or any use in last two weeks of strong CYP3A-enzyme inducers/inhibitors and/or strong UGT1A inhibitors
- •Known hypersensitivity to any of the components of Onivyde other liposomal irinotecan formulations, irinotecan, fluoropyrimidines, or leucovorin.
- •Breast feeding, known pregnancy, positive serum pregnancy test or unwillingness to use an effective method of contraception, during therapy and for 3 months following the last dose of Onivyde. Females of Childbearing Potential must either agree to use and be able to take effective contraceptive birth control measures (Pearl Index < 1) or agree to practice complete abstinence from heterosexual intercourse during the course of the study and for at least 3 months after last application of program treatment. A female subject is considered to be of childbearing potential unless she is age ≥ 50 years and naturally amenorrhoeic for ≥ 2 years, or unless she is surgically sterile. Males must agree not to father a child (including not donating sperm) during the course of the trial and for at least 6 months after last administration of study drugs.
- •Previous treatment with combination drug tegafur, gimeracil, and oteracil potassium with seven days before enrollment.
- •Current treatment with Sorivudine.
- •Severe fatigue or bone marrow depression after prior radiotherapy or antineoplastic therapy
- •Pregnancy or women with child-bearing potential or lactating
- •Non-malignant severe co-morbidity
- •Previous second-line anti-cancer therapy (e.g., Tegafur)
- •History of other malignancy with a disease-free interval <5 years (Registration is permitted if it has minimal impact on prognosis, such as carcinoma in situ and papillary thyroid cancer)
- •History or current eveidence of brain metastasis
研究组 & 干预措施
5FU/LV
dl-LV 400mg/m2 or l-LV 200mg/m2 (30 minutes), 5-FU 2400 mg/m2 (46 hours) IV every 2 weeks.
干预措施: 5-FU/LV (Drug)
5-FU/LV/Onivyde
Onivyde 70 mg/m2 (90 minutes), dl-LV 400mg/m2 or l-LV 200mg/m2 (30 minutes), 5-FU 2400 mg/m2 (46 hours) IV every 2 weeks.
干预措施: Onivyde (Drug)
5-FU/LV/Onivyde
Onivyde 70 mg/m2 (90 minutes), dl-LV 400mg/m2 or l-LV 200mg/m2 (30 minutes), 5-FU 2400 mg/m2 (46 hours) IV every 2 weeks.
干预措施: 5-FU/LV (Drug)
结局指标
主要结局
Progression Free Survival by independent central reviewer
时间窗: from the date of enrollment to the earlier of the date of confirmed progression or death from any cause. (assessed up to 36 months)
Progression-free survival is the time from the date of enrollment to the earlier of the date of confirmed progression or death from any cause.
次要结局
- Overall Survival(from the date of enrollment to death from any cause. (assessed up to 36 months))
- Response rates determined by the investigator according to the RECIST(Response Evaluation Criteria in Solid Tumors) v1.1(from the date of enrollment to end of treatment. (assessed up to 36 months))
- EORTC-QLQ (European Organization for Research and Treatment of Cancer - Quality of life Questionnaire) C30 (version 3.0)(from the date of Screening to end of treatment. (assessed up to 36 months))
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability](from the date of enrollment to 30 days after last treatment. (assessed up to 36 months))
- Progression Free Survival by investigator assessment(from the date of enrollment to the earlier of the date of confirmed progression or death from any cause. (assessed up to 36 months))
- Response rates determined by the independent central reviewer(from the date of enrollment to end of treatment. (assessed up to 36 months))
研究者
Changhoon Yoo
Assistant Professor
Asan Medical Center