RadioEmbolizaTion Using hOlmium-166 in Patients With Unresectable Hepatocellular Carcinoma: Prospective, Open Label, Single-center Pilot Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5.0
研究概览
简要总结
Background: Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancers and represents a growing health problem worldwide. Most patients present locally advanced disease and are candidates for palliative transarterial locoregional treatment. Transarterial radioembolization (TARE) using 90Y has been used for more than a decade for patients with advanced disease. The use of 166Ho could offer a more personalized approach in terms of imaging and dosimetry. Aim: to evaluate the feasibility and safety of TARE using 166Ho in a selected population of HCC patients and assess the biological peripheral response to this therapy. Materials and methods: In this open-label, prospective, non-randomized, singlecenter pilot study, 20 patients with unresectable hepatocellular carcinoma will undergo TARE using 166Ho. The primary outcome is the feasibility of 166Ho radioembolization as well as the assessment of safety and toxicity profiles (CTAE V5.0). Secondary outcomes include the evaluation of efficacy of 166Ho radioembolization in unresectable hepatocellular carcinoma, according to mRECIST and metabolic criteria, as well as the impact on the tumor marker alpha-fetoprotein (AFP), assessment of biodistribution/dosimetry using a "scout dose" and time to progression (TTP). A substudy will assess the hepatic function using 99mTc-IDA hepato-biliary scintigraphy (HBS) and the comparison between "pre-scout" HBS and HBS just after "scout dose". Finally, blood samples will be collected at different time points in order to explore the biological peripheral response to these therapies. Perspectives: The newly developed 166Ho-microspheres have distinctive advantages over the existing 90Ymicrospheres with improved dosimetry that represents a prerequisite for optimal safety and efficacy.
详细描述
Primary liver cancer is a growing health problem worldwide. Hepatocellular carcinoma (HCC) represents more than 90% of primary liver cancers and is considered to be the fifth most common cancer and the second leading cause of cancer-related deaths, with the majority being associated to cirrhosis.
Choosing the most suitable treatment option depends not only on the tumor stage, but also on the severity of the underlying liver disease and performance status. Current guidelines consider the Barcelona Clinic Liver Cancer (BCLC) staging system as the algorithm of choice for tumor staging and therapeutic options, taking into account tumor burden, Child-Pugh class and performance status (ECOG).
Surgical approach, such as resection and liver transplantation, and radiofrequency (RFA) represent the curative treatment options. Despite screening of at-risk populations, most patients are diagnosed with locally advanced disease (BCLC B - intermediate stage) and will not be suitable for curative therapies. Moreover, only HCC within the "Milan" criteria (one nodule < 5 cm or up to three nodules < 3 cm in diameter, without macroscopic vascular invasion or extrahepatic disease) are potential candidates for transplantation. Resection can be proposed only in case of compensated cirrhosis in the absence of portal hypertension and RFA is only possible for small lesions (< 5 cm, < 3 cm in diameter).
Locally advanced HCC is suitable for transarterial locoregional therapies, conducted mostly in a palliative setting. They take advantage on the double vascularization of the liver, with 75% of the parenchymas blood supply coming from the portal vein, while tumor nodules blood supply being almost exclusively provided by the hepatic artery. When macrovascular involvement or extrahepatic disease are discovered, but patients present a good performance status and a compensated liver function (BCLC C), systemic therapy with the tyrosine kinase inhibitor Sorafenib leads to a limited survival benefit, approximately 3 months advantage compared to placebo.
Transarterial chemoembolization (TACE), either conventional (cTACE) or using drug-eluting embolic (DEE) agents, is recommended for patients with BCLC stage B and as "bridging" therapy for liver transplantation candidates while on the waiting list. Furthermore, it has been shown that in selected patients, it can be successfully used as a downstaging treatment to transplantation criteria.
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
- •Patients must have given written informed consent
- •Adults ≥ 18 years-old
- •Typical imaging or biopsy proven HCC according to EASL-EORTC guidelines (1)
- •Unresectable disease, BCLC B, or contraindicated for ablation, resection or transplantation, BCLC A, or BCLC C patients with no extra-hepatic extension, patients on the waiting list for resection or transplantation.
- •At least one measurable lesion on multiphasic CT or MRI
- •Preserved liver function with Child- Pugh score≤ B7
- •ECOG performance status ≤ 1 (Table 2)
- •Life expectancy ≥3 months
- •Efficient contraception for women
- •Platelets ≥ 50000/m3 and PT≥ 50%
- •Hemoglobin ≥8.5 g/dl
- •Bilirubin ≤ 2 mg/dl
- •ASAT/ALAT levels ≤ 5x upper normal limit
- •Creatinine ≤ 1.5x upper normal limit
排除标准
- •Before work-up:
- •History of progressive, uncontrolled cancer other than HCC presenting liver metastasis.
- •>50% of liver involvement
- •Portal vein thrombosis of the main branch diagnosed on contrast enhanced images. Involvement of the right or left portal main branches and more distal is accepted
- •Evidence of extrahepatic disease
- •Unmanageable intolerance to contrast medium
- •Contraindication to hepatic angiography
- •Digestive hemorrhage due to portal hypertension in the 30 days preceding treatment
- •Previous systemic treatment, radiation therapy, transarterial loco-regional therapy or ablation therapy for HCC
- •Active infection or untreated active hepatitis (if detectable viral HBV load, treatment with a nucleoside analog should be instituted).
- •Pregnancy or breast feeding
- •Transjugular intrahepatic portosystemic shunt (TIPS) or portacaval shunt
- •Major surgery withing 4 weeks or incompletely healed surgical incision before starting study therapy
- •Patients suffering from psychic disorders that make a comprehensive judgement impossible, such as psychosis, hallucinations and/or severe depression.
- •Patients who are declared incapacitated
- •After work-up:
- •Lung absorbed dose > 30 Gy, as calculated using the 166Ho scout dose or 99mTc MAA
- •Uncorrectable extrahepatic deposition of the scout dose activity. Activity in the falciform ligament, portal lymph nodes and gallbladder is accepted.
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5.0
时间窗: 6 months
% of patients with change in clinical, biological and radiological parameters
Achievement of the selective radioembolization with Holmium-166 treatment in patients with HCC
时间窗: immediately after the SIRT session
Feasibility will be measured by the number of completed treatments and the percentage of injected activity compared to simulation
次要结局
- Evaluation of tumor response marker alpha-fetoprotein(Baseline,1,3,6 Months)
- Time to progression (TTP)(6 months)
- Microsphere concentration derived from 1.5T MRI R2* relaxivity measurements(Baseline and immediately after the intervention)
- Evaluation of efficacy of 166Ho radioembolization in unresectable hepatocellular carcinoma, according to mRECIST(3 months)
- Evaluation of efficacy of 166Ho radioembolization in unresectable hepatocellular using metabolic assessments (FDG and choline PET/CT)(3 months)
- Evaluation of biodistribution/dosimetry using a scout dose(Day 5)