Prospective, Multicenter, Randomized, Controlled Study Evaluating SIR-Spheres Y-90 Resin Microspheres Preceding Cisplatin-gemcitabine (CIS-GEM) Chemotherapy Versus CIS-GEM Chemotherapy Alone as First-line Treatment of Patients With Unresectable Intrahepatic Cholangiocarcinoma
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 89
- 试验地点
- 23
- 主要终点
- Survival at 18 Months
研究概览
简要总结
The study planned to evaluate the benefit of applying Selective Internal Radiation Therapy (SIRT) using SIR-Spheres Y-90 resin microspheres prior to receiving systemic chemotherapy treatment (cisplatin-gemcitabine, or CIS-GEM) in patients with unresectable intrahepatic cholangiocarcinoma. Half of the patients were randomized to CIS-GEM chemotherapy plus SIRT, and half of the patients were randomized to CIS-GEM alone.
详细描述
This clinical study was a prospective, multicenter, randomized, controlled study evaluating SIR-Spheres Y-90 resin microspheres followed by cisplatin-gemcitabine (CIS-GEM) chemotherapy vs. CIS-GEM chemotherapy alone as first-line treatment of patients with unresectable intrahepatic cholangiocarcinoma.
Randomized patients were to be followed until death, withdrawal of consent, or until end of study.
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
- •Willing, able and mentally competent to provide written informed consent.
- •Aged 18 years or older.
- •Histologically or cytologically confirmed unresectable and non-ablatable intrahepatic cholangiocarcinoma.
- •Liver-only or liver predominant intrahepatic cholangiocarcinoma. Patient are permitted to have loco-regional lymph node involvement defined as: portal LN </= to 2 cm and/or para aortic LN </= to 1.5 cm in longest diameter, and/or up to 2 indeterminate lung lesions < 1 cm if these lung lesions are positron emission tomography (PET) negative.
- •Chemotherapy naïve. Adjuvant chemotherapy is not permitted.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or
- •Adequate hematological function defined as:
- •Hemoglobin >/= 10g/dL White Blood Cell count (WBC) >/= 3.0 x 10^9/L Absolute neutrophil count (ANC) >/= 1.5 x 10^9/L Platelet count >/= 100,000/mm^3 - Adequate liver function defined as: Total bilirubin </= 30 umol/L (1.75 mg/dL) Albumin >/= 30 g/L
- •Adequate renal function defined as: Serum urea and serum creatinine < 1.5 times upper limit of normal (ULN) Creatinine clearance >/= 45 ml/min (calculated with Cockcroft-Gault Equation)
- •Life expectancy of at least 3 months without any active treatment
- •Female patients must either be postmenopausal, sterile (surgically or radiation- or chemically-induced), or if sexually active use an acceptable method of contraception during the study.
- •Male patients must be surgically sterile or if sexually active must use an acceptable method of contraception during the study.
- •Considered suitable to receive either regimen in the clinical judgement of the treating investigator.
排除标准
- •Patients with only non-measurable lesions in the liver according to RECIST criteria
- •Incomplete recovery from previous liver surgery, e.g. unresolved biliary tree obstruction or biliary sepsis or inadequate liver function
- •Biliary stent in situ
- •Main trunk Portal Vein Thrombosis (PVT)
- •Ascites, even if controlled with diuretics. (A minor peri-hepatic rim of ascites detected at imaging is acceptable).
- •Mixed hepatocellular carcinoma - intrahepatic cholangiocarcinoma (HCC-ICC) disease
- •History of prior malignancy. Exceptions include in-situ carcinoma of the cervix treated by cone-biopsy/resection, non-metastatic basal and/or squamous cell carcinomas of the skin, recurrent intra-hepatic cholangiocarcinoma post local treatment or any early stage (stage 1) malignancy adequately resected with curative intent at least 5 years prior to study entry
- •Suspicion of any bone metastasis/metastases or central nervous system metastasis/metastases on clinical or imaging examination.
- •Prior internal or external radiation delivered to the liver.
- •Pregnancy; breast feeding.
- •Participation within 28 days prior to randomization, in an active part of another clinical study that would compromise any of the endpoints of the study.
- •Evidence of ongoing active infection that may affect treatment feasibility or outcome.
- •Prior Whipple's procedure.
研究组 & 干预措施
Chemotherapy (Cisplatin-Gemcitabine)
Cisplatin 25mg/m2 in 1000ml 0.9% saline given over 1 hour followed by 500 ml 0.9% saline over 30 minutes, followed by Gemcitabine 1000 mg/m2 in 250-500 ml 0.9% saline over 30 minutes by intravenous infusions on days 1, and 8 of a 21-day cycle.
干预措施: Cisplatin-gemcitabine (Drug)
Radiation: SIRT + chemotherapy (Cisplatin-Gemcitabine)
A single treatment of hepatic arterial injection of SIR-Spheres Y-90 resin microspheres (SIRT) followed 14-16 days later by systemic chemotherapy (ABC-02 CIS-GEM protocol) with an intention to treat with 8 cycles of cisplatin + gemcitabine, or until progression, toxicity or patient choice. Treatment may be continued beyond 8 cycles in the absence of significant disease progression, at the treating clinicians' discretion.
干预措施: Cisplatin-gemcitabine (Drug)
结局指标
主要结局
Survival at 18 Months
时间窗: 18 months following the date of randomization.
Survival at 18 months is defined as the proportion of patients still alive 18 months from the date of randomization. The outcome was analyzed but the clinical database is not deemed to be reliable.
次要结局
- Liver-specific Progression Free Survival (PFS)(From date of randomization to the first documented date of progression in the liver or date of death from any cause, assessed up to 36 months..)
- Progression Free Survival (PFS) at Any Site(From date of randomization to the date of progression at any site until the first date of documented tumor progression at any site or date of death from any cause, assessed up to 36 months.)
- Objective Response Rate by RECIST 1.1 and Refined RECIST - Liver(From the date of first treatment until the date of date of first documented progression in the liver, assessed up to 36 months.)
- Objective Response Rate by RECIST 1.1 and Refined RECIST - at Any Site(From the date of first treatment until progression at any site, assessed up to 36 months.)
- Overall Survival(From date of randomization until the date of death from any cause, assessed up to 36 months.)
- Liver Surgical Resection and Ablation Rate(18 months following the date of randomization.)
- Incidence of Adverse Events (Safety and Tolerability)(Informed consent until 28 days post last dose of protocol chemotherapy.)