A Phase II Study to Evaluate the Efficacy and Safety of Y-90, Durvalumab, Tremelimumab, and Zanzalintinib in Patients With Unresectable and Locally-Advanced Hepatocellular Carcinoma
概览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Proportion of progression-free at 6-months
概览
简要总结
This phase II trial tests how well giving Y-90 radioembolization, durvalumab, tremelimumab and zanzalintinib works for the treatment of hepatocellular carcinoma that cannot be removed by surgery (unresectable) and that has spread to nearby tissue or lymph nodes (locally advanced). Y-90 radioembolization is a therapy that injects radioactive particles directly into an artery that feeds liver tumors to cut off their blood supply. Immunotherapy with monoclonal antibodies, such as durvalumab and tremelimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Zanzalintinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving Y-90 radioembolization, durvalumab, tremelimumab and zanzalintinib may be effective for treating unresectable and locally-advanced hepatocellular carcinoma.
详细描述
PRIMARY OBJECTIVE:
I. To assess proportion of participants that are progression-free at 6 months.
SECONDARY OBJECTIVES:
I. To assess safety of study intervention. II. To estimate objective response rate (ORR) for study intervention. III. To estimate disease control rate (DCR) for study intervention. IV. To estimate time to disease progression (TTP) for study intervention. V. To estimate progression-free survival. VI. To estimate overall survival (OS) for study intervention.
EXPLORATORY OBJECTIVE:
I. To evaluate therapy induced changes in the tumor and tumor immune microenvironments.
OUTLINE:
CYCLE 1: Patients receive tremelimumab intravenously (IV) and durvalumab IV, over 60 minutes, on day 1. 7-14 days later patients undergo transarterial radioembolization with yttrium (Y)-90 in the absence of disease progression or unacceptable toxicity. 7 days to 12 weeks later patients proceed to cycle 2.
CYCLE 2-12: Patients receive durvalumab IV, over 30-60 minutes, on day 1 and zanzalintinib orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.
Patients undergo angiogram during screening and undergo single photon emission computed tomography (SPECT), computed tomography (CT) scan or magnetic resonance imaging (MRI), and blood and urine sample collection throughout the study. Patients optionally undergo tumor biopsy throughout the study.
After completion of study treatment, patients are followed up at 100 days and every 6 months for 1 year.
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
- •Participant must provide written informed consent before any study-specific procedures or interventions are performed
- •Participants aged ≥ 18 years
- •Body weight \> 30 kg
- •Patients must have radiologically, or histologically or cytologically confirmed hepatocellular cancer that is not amenable to transplant or resection:
- •Barcelona Clinic Liver Cancer Stage B or C
- •Cirrhosis grade of Child-Pugh (CP) A or CP-B7 (excluding albumin-bilirubin \[ALBI\] grade 3)
- •Fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible
- •Disease must not be amenable to surgical resection, transplantation, or thermal ablation, or recurrent hepatocellular carcinoma (HCC) after a previous definitive therapy (surgery or thermoablative therapy)
- •Venous invasion (portal, hepatic, biliary) and infiltrative growth pattern are eligible
- •Eligible for Y-90 transarterial radioembolization (TARE) based on planning angiogram, with evidence of:
排除标准
- •Another primary tumor
- •Extrahepatic metastases
- •Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment.
- •Note: Eligible participants must be neurologically asymptomatic and without corticosteroid treatment at the time of enrollment.
- •Note: Base of skull lesions without definitive evidence of dural or brain parenchymal involvement are allowed
- •Prior systemic therapy for HCC
- •Prior Y-90 radioembolization
- •Note: prior transarterial chemoembolization is permitted if \> 6 months prior to enrollment
- •Advanced liver disease with a CP-B7 (ALBI grade 3), CP-B8, CP-B9 or CP- C, or active gastrointestinal bleeding or encephalopathy or refractory ascites
- •Radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible
研究组 & 干预措施
Treatment (Y-90, tremelimumab, durvalumab, zanzalintinib)
CYCLE 1: Patients receive tremelimumab IV and durvalumab IV, over 60 minutes, on day 1. 7-14 days later patients undergo transarterial radioembolization with Y-90 in the absence of disease progression or unacceptable toxicity. 7 days to 12 weeks later patients proceed to cycle 2.
CYCLE 2-12: Patients receive durvalumab IV, over 30-60 minutes, on day 1 and zanzalintinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.
Patients undergo angiogram during screening and undergo SPECT, CT scan or MRI, and blood and urine sample collection throughout the study. Patients optionally undergo tumor biopsy throughout the study.
干预措施: Magnetic Resonance Imaging (Procedure)
Treatment (Y-90, tremelimumab, durvalumab, zanzalintinib)
CYCLE 1: Patients receive tremelimumab IV and durvalumab IV, over 60 minutes, on day 1. 7-14 days later patients undergo transarterial radioembolization with Y-90 in the absence of disease progression or unacceptable toxicity. 7 days to 12 weeks later patients proceed to cycle 2.
CYCLE 2-12: Patients receive durvalumab IV, over 30-60 minutes, on day 1 and zanzalintinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.
Patients undergo angiogram during screening and undergo SPECT, CT scan or MRI, and blood and urine sample collection throughout the study. Patients optionally undergo tumor biopsy throughout the study.
干预措施: Angiogram (Procedure)
Treatment (Y-90, tremelimumab, durvalumab, zanzalintinib)
CYCLE 1: Patients receive tremelimumab IV and durvalumab IV, over 60 minutes, on day 1. 7-14 days later patients undergo transarterial radioembolization with Y-90 in the absence of disease progression or unacceptable toxicity. 7 days to 12 weeks later patients proceed to cycle 2.
CYCLE 2-12: Patients receive durvalumab IV, over 30-60 minutes, on day 1 and zanzalintinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.
Patients undergo angiogram during screening and undergo SPECT, CT scan or MRI, and blood and urine sample collection throughout the study. Patients optionally undergo tumor biopsy throughout the study.
干预措施: Biopsy Procedure (Procedure)
Treatment (Y-90, tremelimumab, durvalumab, zanzalintinib)
CYCLE 1: Patients receive tremelimumab IV and durvalumab IV, over 60 minutes, on day 1. 7-14 days later patients undergo transarterial radioembolization with Y-90 in the absence of disease progression or unacceptable toxicity. 7 days to 12 weeks later patients proceed to cycle 2.
CYCLE 2-12: Patients receive durvalumab IV, over 30-60 minutes, on day 1 and zanzalintinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.
Patients undergo angiogram during screening and undergo SPECT, CT scan or MRI, and blood and urine sample collection throughout the study. Patients optionally undergo tumor biopsy throughout the study.
干预措施: Biospecimen Collection (Procedure)
Treatment (Y-90, tremelimumab, durvalumab, zanzalintinib)
CYCLE 1: Patients receive tremelimumab IV and durvalumab IV, over 60 minutes, on day 1. 7-14 days later patients undergo transarterial radioembolization with Y-90 in the absence of disease progression or unacceptable toxicity. 7 days to 12 weeks later patients proceed to cycle 2.
CYCLE 2-12: Patients receive durvalumab IV, over 30-60 minutes, on day 1 and zanzalintinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.
Patients undergo angiogram during screening and undergo SPECT, CT scan or MRI, and blood and urine sample collection throughout the study. Patients optionally undergo tumor biopsy throughout the study.
干预措施: Computed Tomography (Procedure)
Treatment (Y-90, tremelimumab, durvalumab, zanzalintinib)
CYCLE 1: Patients receive tremelimumab IV and durvalumab IV, over 60 minutes, on day 1. 7-14 days later patients undergo transarterial radioembolization with Y-90 in the absence of disease progression or unacceptable toxicity. 7 days to 12 weeks later patients proceed to cycle 2.
CYCLE 2-12: Patients receive durvalumab IV, over 30-60 minutes, on day 1 and zanzalintinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.
Patients undergo angiogram during screening and undergo SPECT, CT scan or MRI, and blood and urine sample collection throughout the study. Patients optionally undergo tumor biopsy throughout the study.
干预措施: Single Photon Emission Computed Tomography (Procedure)
Treatment (Y-90, tremelimumab, durvalumab, zanzalintinib)
CYCLE 1: Patients receive tremelimumab IV and durvalumab IV, over 60 minutes, on day 1. 7-14 days later patients undergo transarterial radioembolization with Y-90 in the absence of disease progression or unacceptable toxicity. 7 days to 12 weeks later patients proceed to cycle 2.
CYCLE 2-12: Patients receive durvalumab IV, over 30-60 minutes, on day 1 and zanzalintinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.
Patients undergo angiogram during screening and undergo SPECT, CT scan or MRI, and blood and urine sample collection throughout the study. Patients optionally undergo tumor biopsy throughout the study.
干预措施: Yttrium-90 Microsphere Radioembolization (Procedure)
Treatment (Y-90, tremelimumab, durvalumab, zanzalintinib)
CYCLE 1: Patients receive tremelimumab IV and durvalumab IV, over 60 minutes, on day 1. 7-14 days later patients undergo transarterial radioembolization with Y-90 in the absence of disease progression or unacceptable toxicity. 7 days to 12 weeks later patients proceed to cycle 2.
CYCLE 2-12: Patients receive durvalumab IV, over 30-60 minutes, on day 1 and zanzalintinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.
Patients undergo angiogram during screening and undergo SPECT, CT scan or MRI, and blood and urine sample collection throughout the study. Patients optionally undergo tumor biopsy throughout the study.
干预措施: Tremelimumab (Biological)
Treatment (Y-90, tremelimumab, durvalumab, zanzalintinib)
CYCLE 1: Patients receive tremelimumab IV and durvalumab IV, over 60 minutes, on day 1. 7-14 days later patients undergo transarterial radioembolization with Y-90 in the absence of disease progression or unacceptable toxicity. 7 days to 12 weeks later patients proceed to cycle 2.
CYCLE 2-12: Patients receive durvalumab IV, over 30-60 minutes, on day 1 and zanzalintinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.
Patients undergo angiogram during screening and undergo SPECT, CT scan or MRI, and blood and urine sample collection throughout the study. Patients optionally undergo tumor biopsy throughout the study.
干预措施: Zanzalintinib (Drug)
Treatment (Y-90, tremelimumab, durvalumab, zanzalintinib)
CYCLE 1: Patients receive tremelimumab IV and durvalumab IV, over 60 minutes, on day 1. 7-14 days later patients undergo transarterial radioembolization with Y-90 in the absence of disease progression or unacceptable toxicity. 7 days to 12 weeks later patients proceed to cycle 2.
CYCLE 2-12: Patients receive durvalumab IV, over 30-60 minutes, on day 1 and zanzalintinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.
Patients undergo angiogram during screening and undergo SPECT, CT scan or MRI, and blood and urine sample collection throughout the study. Patients optionally undergo tumor biopsy throughout the study.
干预措施: Durvalumab (Biological)
结局指标
主要结局
Proportion of progression-free at 6-months
时间窗: From first dose of study intervention, up to 6 months
Will be reported with 95% exact confidence interval.
次要结局
- Incidence of grade ≥ 3 adverse events (AEs)(From first dose of study intervention to 30 days for AEs or 100 days for serious adverse events (SAEs) from last dose of study intervention)
- Objective response rate(From first dose of study intervention to last dose of study intervention)
- Disease control rate(From first dose of study intervention to date of progression up to 12 months from last dose of study intervention)
- Time to progression (TTP)(From first dose of study intervention to date of progression up to 12 months from last dose of study intervention)
- Progression free survival(From first dose of study intervention to date of progression or death (any cause) up to 12 months from last dose of study intervention)
- Overall survival(From first dose of study intervention to date of death (any cause) up to 12 months from last dose of study intervention)
研究者
Adel Kardosh M.D., Ph.D.
Principal Investigator
OHSU Knight Cancer Institute