NCT03033446已完成2 期
A Phase II Open-Label, Single Centre, Non-Randomised Trial Of Y90-Radioembolization In Combination With Nivolumab In Asian Patients With Advanced Hepatocellular Carcinoma
National Cancer Centre, Singapore2 个研究点 分布在 1 个国家目标入组 40 人开始时间: 2016年12月20日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Response Rate
研究概览
简要总结
The purpose of this study is to evaluate the effect of liver-localised radioembolization and nivolumab on liver cancer.
详细描述
The hypothesis is that liver-localized radioembolization will stimulate tumour and/or HBV specific T cell responses that are associated with favourable patient outcomes and that can be boosted using nivolumab anti-PD1 checkpoint blockade immunotherapy.
Primary objective
To evaluate the response rates of Y90 radioembolization in combination with nivolumab in HCC
Secondary objectives
- To evaluate time to response, response duration, time to treatment progression and sites of progression when RE is combined with nivolumab
- To assess progression free survival and overall survival when RE is combined with nivolumab
- To assess the quality of life using the FACT-HEP score and EORTC QLQ-C30
- To assess the safety and tolerability of the combination of RE and nivolumab
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
- 21 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with hepatocellular carcinoma (HCC) that is not suitable for resection or liver transplant, who are planned for Y90 radioembolization as per institutional practice.
- •Patients must have measurable disease with target lesion in liver, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan.
- •Diagnosis of HCC confirmed by histology/cytology or clinically by AASLD criteria in cirrhotic subjects. Patients without cirrhosis require histological confirmation of diagnosis
- •No prior Y90 radioembolization therapy. Prior local therapies, such as surgery, hepatic artery embolization/chemoembolization, radiofrequency ablation, percutaneous ethanol injection or cryoabalastion is allowed, if the index lesion(s) remains outside of the treatment field or has progressed since prior treatment. Local therapy must have been completed at least 4 weeks prior to the baseline scan
- •Age ≥ 21 years.
- •ECOG performance status ≤ 2
- •Life expectancy of greater than 3 months
- •Only patients with Child-Pugh score for liver cirrhosis of A (sum of scores for five parameters: 5-6) will be allowed into this trial
- •Subjects with HBV infection must be on antiviral therapy per regional standard of care guidelines prior to initiation of study therapy. Both HBeAg positive and negative subjects will be included.
- •Patients must have lesions in the liver that are amenable to CT-guided liver biopsy
- •Patients must have normal organ and marrow function as defined below:
- •Haemoglobin ≥ 8.5g/dL
- •Absolute Neutrophil Count ≥ 1.5 x 10^9/L
- •Platelets ≥ 50 x 10^9/L
- •Total Bilirubin < 3 mg/dL
- •AST(SGOT)/ALT (SGPT) ≤ 3 x ULN
- •Creatinine ≤ 1.5 x ULN or measured/calculated Creatinine Clearance (CrCl) ≥ 60 ml/min
- •Ability to understand and the willingness to sign a written informed consent document.
- •Any surgery must be more than 28 days before start of study drug and any surgical wounds must be completely healed
- •Female subjects of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to receiving the first dose of study medication, and must agree to adequate contraception use from time of signing the informed consent through to 120 days after the last dose of the study drug. Male subjects must agree to adequate contraception use from time of signing the informed consent through 120 days after the last dose of the study drug.
排除标准
- •Patients are excluded if they are receiving any other investigational agents or using an investigational device within 4 weeks of first dose of treatment. Patients are excluded if they are receiving other systemic therapy within 2 weeks of first dose of treatment.
- •Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- •Prior use of anti-PD1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any drug specifically targeted T-cell costimulatory checkpoint pathways
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension or psychiatric illness/social situations that would limit compliance with study requirements.
- •Subjects with any active autoimmune disease or history of known or suspected autoimmune disease requiring systemic therapy within the past 2 years, except for subjects with vitiligo, resolved childhood asthma/atopy or euthyroid patients with a history of Grave's disease (subjects with suspected autoimmune thyroid disorders must be negative for thyroglobulin and thyroid peroxidase antibodies and thyroid stimulating immunoglobulin prior to randomization). Replacement therapy (e.g. with thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency etc) is not considered a form of systemic treatment
- •Pregnant women or breastfeeding mothers are excluded from this study because of the potential risks to the foetus or baby. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- •Diagnosis of immunodeficiency, including HIV/AIDS
- •Prior organ allograft or allogeneic bone marrow transplantation
- •History of severe hypersensitivity reactions to other monoclonal antibodies.
- •Prisoners or subjects who are involuntarily incarcerated
- •Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness
- •Inability to comply with restrictions and prohibited activities/treatments in this study
- •Chronic treatment with systemic steroids or other immunosuppressive agent.
- •Subjects with concomitant second malignancies (except adequately treated non-melanomatous skin cancers, in situ cervical cancers, localized prostate cancer or in situ breast cancer) are excluded unless a complete remission was achieved at least 3 years prior to study entry and no additional therapy is required or anticipated to be required
- •Prior radiation therapy to the liver or upper abdomen
- •Inability to undergo Y-90 radioembolisation due to inability to cathterise the hepatic artery, portal vein thrombosis/occlusion limiting the ability to perform selective infusion, Tc-99M MAA scan showing unfavourable shunt fraction between the liver and pulmonary parenchyma, any other contraindications to RE as determined by the interventional radiologist (e.g. other anatomic variants precluding safe administration of Y90, severe peripheral vascular disease, uncorrectable coagulopathy etc)
研究组 & 干预措施
Y90-Radioembolization and Nivolumab
Experimental
干预措施: Nivolumab (Drug)
Y90-Radioembolization and Nivolumab
Experimental
干预措施: Y-90 Radioembolization (Radiation)
结局指标
主要结局
Response Rate
时间窗: Tumour assessment at 8 weeks
次要结局
- Time to Response(From date of first dose with Y90 Radioemolization (RE) until best overall response of Complete Response (CR) or Partial Response (PR) is achieved, up to 12 weeks after last dose of Nivolumab)
- Overall Survival(From date of first dose with Y90 RE until death from any cause, up to 2 years)
- Quality of Life using the FACT-HEP score(From date of screening until 3 months after last dose of Nivolumab)
- Quality of Life using EORTC QLQ-C30(From date of screening until 3 months after last dose of Nivolumab)
- Adverse events from the combination of RE and nivolumab assessed by NCI CTCAE v4.0(While receiving study agent and up to 100 days after last dose of Nivolumab)
- Duration of Response(From date of first assessment of CR or PR until the first date that progressive disease or death is documented, up to 2 years)
- Time to Progression(From date of first dose with Y90 RE until the first date that progressive disease is documented, up to 12 weeks after last dose of Nivolumab)
- Progression Free Survival(From date of first dose with Y90 RE until tumour progression, or death from any cause, up to 12 weeks after last dose of Nivolumab)
研究者
研究点 (2)
Loading locations...
相似试验
已完成
2 期
SIR-Spheres® 90Y Microspheres Treatment of Uveal Melanoma Metastasized to LiverStage IV Uveal MelanomaNCT01473004Thomas Jefferson University48
终止
不适用
Radioembolization of Primary and Secondary Liver Malignancies and The Effect On The Immune SystemSecondary Malignant Neoplasm of LiverHepatocellular CarcinomaNCT03889093University of Minnesota14
已完成
不适用
AROMA - Impact of radioembolization of hepatic malignomas on distal not irradiated tumor tissue.C20C19C18Malignant neoplasm of rectumMalignant neoplasm of rectosigmoid junctionMalignant neoplasm of colonDRKS00009744Klinik und Poliklinik für Radiologie Klinikum der Universität München Campus Großhadern64
招募中
不适用
Comparison between Radioembolization and Transarterial chemoembolization in liver cancer treatmenthepatocellular carcinomaC22.0RBR-8w9rzyFaculdade de Medicina de Botucatu/ Universidade Estadual Paulista
进行中（未招募）
2 期
Abscopal Effect of Radiotherapy and Nivolumab in Relapsed Hodgkin Lymphoma After Anti-PD1 TherapyClassical Hodgkin LymphomaNCT03480334University of Cologne26