Holmium-166 Transarterial Radioembolization in Unresectable, Early Stage Hepatocellular Carcinoma; a Prospective, Single-arm, Open Label, Multicenter Phase II Study: HOMIE-166.
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 发起方
- 入组人数
- 6
- 试验地点
- 2
- 主要终点
- confirmed Objective Response Rate (ORR) by localized mRECIST
研究概览
简要总结
166Ho-TARE is a promising modality for the treatment of HCC, given the unique characteristics of holmium, allowing careful patient selection and personalized dosimetry treatment planning. Further clinical evidence is needed to evaluate the safety and efficacy of 166Ho-TARE in the treatment of HCC patients with limited tumor burden, well preserved liver function and performance status and ineligible for liver transplantation and/or liver resection. This study will also provide further evidence on the dose-response relationship of 166Ho-TARE in (early) HCC.
详细描述
This is a prospective, single-arm, open-label, multicenter study with 166Ho-TARE in unresectable HCC patients with limited tumor burden and well-preserved liver function and performance status, ineligible for liver transplantation and/or liver resection. Eligibility for liver transplantation and liver resection is determined by the multidisciplinary tumor board. However, patients eligible for liver transplantation can still be included in the setting of bridge to transplant.
The study proposes to use 166Ho-TARE, including both therapeutic 166Ho-microspheres (QuiremSpheres™ Holmium-166 Microspheres) and scout 166Ho-microspheres (QuiremScout™ Holmium-166 Microspheres). All patients providing informed consent and meeting the selection criteria will be further screened using a scout dose of 166Ho-microspheres to evaluate 166Ho-TARE eligibility. Patients not eligible for selective 166Ho-TARE are considered screen failures and will not be considered as enrolled.
The primary endpoint will be assessed by blinded, independent central review, organized by an imaging core laboratory.
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
- •Age ≥ 18 years
- •Multidisciplinary tumor board decision for locoregional treatment
- •Freely given, written informed consent
- •Patients with unresectable HCC with a single nodule ≤ 8 cm or up to three nodules with a diameter of ≤ 5 cm (each) eligible for selective radioembolization (including position changes of infusion catheters)
- •Non-cirrhotic patients or Child-Pugh A cirrhosis
- •ECOG performance status 0-1
- •Using an acceptable method of contraception throughout the study until survival follow up (for subjects of childbearing potential)
- •Adequate hematological, renal and liver function.
- •Adequate hematological function defined as:
- •Hemoglobin ≥ 6 mmol/L (9.7 g/dL)
- •WBC ≥ 3.0 x 10E9/L
- •Absolute neutrophil count ≥ 1.5 x 10E9/L
- •Platelet count ≥ 50,000/mm3
- •Adequate renal function defined as:
- •Serum urea and serum creatinine < 1.5 times upper limit of normal (ULN)
- •Creatinine clearance ≥ 45 ml/min
- •Adequate liver function defined as:
- •Total bilirubin ≤ 35µmol/L (2.05 mg/dL)
- •Albumin ≥ 30 g/L
- •AST and ALT ≤ 5X ULN
排除标准
- •Diffuse and/or infiltrative HCC (defined as HCC consisting of multiple tiny liver nodules spreading throughout the entire liver or entire lobe, without a dominant nodule)
- •Hypoperfused HCC (defined as a lack of tumor blush (i.e. reduced or no uptake of contrast fluid) observed on the intra-procedural CT)
- •No full, selective arterial coverage on intra-procedural CT
- •Life expectancy < 6 months
- •Child-Pugh score ≥7 points
- •Prior liver transplantation
- •Prior locoregional or systemic anti-cancer therapy for HCC and previous malignancies
- •Macrovascular invasion (defined as macrovascular invasion of the hepatic and/or portal vein main branches)
- •Extrahepatic metastases
- •Clinically significant ascites
- •Hepatic encephalopathy
- •Untreated active hepatitis B and/or C
- •Work-up imaging showing:
- •Lung shunt > 30 Gy is simulated on 166Ho-scout imaging; or
- •Uncorrectable extrahepatic deposition of simulated 166Ho-scout dose activity. Activity in the falciform ligament, portal lymph nodes and gallbladder is accepted; or
- •Anticipated ineffective tumor targeting (< 150 Gy mean tumor simulated absorbed dose) of 166Ho-scout for each lesion; or
- •Entire tumor burden not within the perfused liver volume (possible extrahepatic collateral supply of the tumor); or
- •Perfused liver volume > 50% of whole liver tissue
- •Pregnant or breast-feeding
- •Current or history of cancer other than HCC, except adequately treated non-melanoma skin cancer or carcinoma in situ of the cervix
- •In the Investigator's opinion there is a reason that could limit the patient's ability to participate in the study, compliance with follow-up requirements or impact the scientific integrity of the study
- •Concurrently enrolled in another study, unless it is an observational non-interventional study
结局指标
主要结局
confirmed Objective Response Rate (ORR) by localized mRECIST
时间窗: 5 years
ORR is defined as the proportion of patients achieving either complete or partial tumor response during the study, as assessed by blinded central image review according to localized mRECIST
次要结局
- Best and confirmed ORR based on mRECIST(5 years)
- Best ORR based on localized mRECIST(5 years)
- Duration of Response (DoR) ≥ 6 months based on localized mRECIST and mRECIST(5 years)
- Liver resection rate(5 years)
- hepatic Progression-Free Survival (hPFS)(5 years)
- Liver transplantation rate(5 years)
- Overall survival (OS)(5 years)
- Safety and toxicity by evaluating the number of adverse events and the number of patients with each event(5 years)
- Liver function during follow-up ALBI score(5 years)
- Liver function during follow-up using Child Pugh score(5 years)
- Progression-Free Survival (PFS)(5 years)
- Time to Progression (TTP)(5 years)
- Liver function during follow-up using MELD score(5 years)
- Quality of Life using EQ-5D-5L questionnaire(1 year)
- Assessment of dosimetry and biodistribution based on quantitative assessment of imaging scans(5 years)