NCT04541173终止2 期
A Randomized Phase II Study of Atezolizumab and Bevacizumab With Y-90 TARE in Patients With Unresectable Hepatocellular Carcinoma (HCC)
Aiwu Ruth He, MD6 个研究点 分布在 1 个国家目标入组 6 人开始时间: 2020年11月30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
- 终止
- 发起方
- 入组人数
- 6
- 试验地点
- 6
- 主要终点
- Progression Free Survival (PFS) by RECIST 1.1
研究概览
简要总结
This is an open-label, multi-center, randomized phase II study comparing the Y90 TARE followed by bevacizumab and atezolizumab treatment to the Y90 TARE treatment alone in unresectable advanced stage HCC.
详细描述
Subjects will be randomized to Y-90 TARE alone (Arm A) or Y-90 TARE followed by the combination of atezolizumab and bevacizumab (Arm B). The first 10 subjects randomized to Arm B (Y-90 TARE + bevacizumab + atezolizumab) will be assessed for safety after two cycles. If there are no Grade ≥ 3 unexpected toxicities; possibly, probably or definitely related to TARE in combination with bevacizumab and atezolizumab the combination will be deemed safe and accrual will resume.
Subjects randomized to receive bevacizumab and atezolizumab (Arm B) will start the combination of bevacizumab and atezolizumab 4 weeks (± 1 week) after TARE treatment. Full recovery from the procedure is required prior to systemic treatment:
- AST and ALT ≤ 5 x upper limit of normal (ULN) and total bilirubin ≤ 3 mg/dL
- Manifestations of post-embolization syndrome (e.g., fever, nausea, vomiting, and abdominal pain) have resolved to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 Grade 1
- No significant medical events (e.g., gastrointestinal [GI] bleeding, cardiac events, hepatorenal syndrome) during or after the TARE procedure.
Arm B subjects will continue the study drugs for a total of 24 months from the TARE treatment, until intolerable toxicity or disease progression occur.
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
- •Subject must meet all of the following applicable inclusion criteria to participate in this study:
- •Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately. Patients must be willing and able to provide written informed consent for this trial.
- •Age ≥ 18 years at the time of consent.
- •ECOG Performance Status of 0-1 at screening
- •Histological or cytological evidence/confirmation per AJCC, 8th edition, of hepatocellular carcinoma (HCC).
- •Measurable disease by RECIST 1.
- •Patients must have a Child-Pugh score of A. or selected B
- •NOTE: Definition of the selected B7 patients: Child Pugh B7 patients are allowed if they meet the inclusion criteria 11 and they do not have hepatic encephalopathy or more than a moderate amount of ascites.
- •Patients must have at least Barcelona Clinic Liver Cancer (BCLC) stage B HCC and must be outside of Milan Criteria; and/or HCC peripheral vascular involvement of any size or number of tumor (segment peripheral, vp1 and vp2 are allowed, but vp3 and vp4 are excluded). NOTE: absence of extrahepatic spread, must be confirmed by computed tomography (CT) or magnetic resonance imaging (MRI) scan of the chest, abdomen, and pelvis.
- •Patient must either (1) not be a candidate for liver transplantation as determined by the liver transplant service or (2) refuse evaluation for transplantation.
- •Archival tissue obtained within 6 months of registration is required. If archival tissue is not available, subjects are not eligible.
- •No prior systemic therapy is permitted. NOTE: Patients who received prior local therapy (e.g., radiofrequency ablation, percutaneous ethanol or acetic acid injection, cryoablation, high-intensity focused ultrasound or TACE) are eligible provided the target lesion(s) have not been previously treated with local therapy or the target lesion(s) within the field of local therapy have subsequently progressed in accordance with RECIST 1.
- •Prior TACE is allowed if FLR is ≥ 40%.
- •Patient must be a TARE candidate, as defined by a lung dose threshold for Y-90 of 30Gy and an estimated (future liver remnants) FLR of ≥ 40% at the time of forming the comprehensive treatment plan. Both the lung dose threshold and FLR values must be obtained and available in source documentation.
- •Patients must demonstrate adequate hepatic, bone marrow, and renal function as defined below. All screening labs should be performed within 14 days of treatment initiation.
- •Hematological
- •Lymphocyte Count: 500/μL
- •Absolute Neutrophil Count (ANC): ≥ 1,500 /μL
- •Hemoglobin (Hgb): ≥ 9 g/dL without transfusion or EPO dependency (within 7 days of assessment)
- •Platelet count (Plt): ≥ 75,000 / μL
- •--Serum creatinine OR Measured or calculated CrCl (GFR can also be used in place of creatinine or CrCl): ≤ 1.5 X upper limit of normal (ULN) OR ≥ 60 mL/min for subject with creatinine levels > 1.5 x institutional ULN
- •Bilirubin: ≤ 3.0
- •Aspartate aminotransferase (AST): ≤ 5 X ULN for subjects with cancer in liver
- •Alanine aminotransferase (ALT): ≤ 5 X ULN for subjects with cancer in liver
- •Albumin: > 2.5 mg/dL
- •Urine Protein: Urine dipstick for proteinuria ≤ 2 g (within 14 days prior to initiation of study treatment). Patients discovered to have >2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate < 1 g of protein in 24 hours.
- •Coagulation
- •--International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT): ≤ 1.5 X ULN
- •Calcium-Subjects with uncontrolled or symptomatic hypercalcemia are NOT eligible
- •Ionized Calcium: < 1.5 mmol/L
- •Serum Calcium OR Corrected serum calcium: < 12 mg/dL OR < ULN
- •Documented virology status of HIV; NOTE: Patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count ≥ 200/µL, and have an undetectable viral load.
- •Documented virology status of hepatitis, as confirmed by screening HBV and HCV serology test: For patients with active hepatitis B virus (HBV): HBV DNA <500 IU/mL obtained within 28 days prior to initiation of study treatment, and Anti-HBV treatment (per local standard of care; e.g., entecavir) for a minimum of 14 days prior to study entry and willingness to continue treatment for the length of the study.
- •Subjects with chronic infection by HCV who are untreated or who failed previous therapies for HCV are allowed on study. In addition, subjects with successful HCV treatment (defined as sustained virologic response [SVR] 12 or SVR 24) are allowed as long as patients are not actively receiving anti-HCV treatment at the time of study enrollment. Investigators can stop anti-HCV treatment at their discretion prior to enrolling patients on study.
- •Females of childbearing potential must have a negative serum pregnancy test within 14 days prior to study treatment. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months.
- •Female participants of childbearing potential must be willing to abstain from heterosexual intercourse or to use contraception as outlined in Section 5.
- •Male participants capable of fathering children must be willing to abstain from heterosexual intercourse or to use contraception as outlined in Section 5.
- •As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.
- •Exclusion Criteria
- •Subjects meeting any of the criteria below may not participate in the study:
- •Have signs of liver failure, e.g. clinically significant ascites, encephalopathy, or variceal bleeding within six months from enrollment.
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Patients with indwelling catheters (e.g., PleurX® are allowed.
- •Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high-risk for bleeding.
- •Prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment. NOTE: Patients must undergo an esophagogastroduodenoscopy (EGD), and all size of varices (small to large) must be assessed and treated per local standard of care prior to enrollment. Patients who have undergone an EGD within 6 months of prior to initiation of study treatment do not need to repeat the procedure.
- •Have evidence of excessive hepatopulmonary shunting (> 20% in 99mTc macro-aggregated albumin scan for resin and 30 Gy per treatment for glass) or angiographically demonstrable and non-occludable gastrointestinal shunting, precluding from Y-90 treatment.
- •Inadequately controlled arterial hypertension (defined as systolic blood pressure (BP) ≥ 150 mmHg and/or diastolic blood pressure > 100 mmHg), based on an average of ≥ 3 BP readings on ≥ 2 sessions. NOTE: Anti-hypertensive therapy to achieve these parameters is allowable.
- •Prior history of hypertensive crisis or hypertensive encephalopathy.
- •Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina.
- •Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
- •Major surgery within 4 weeks prior to registration or anticipation of a major surgical procedure during study.
- 另有 39 项未显示
排除标准
- 未提供
研究组 & 干预措施
Arm A
Active Comparator
TARE alone
干预措施: Y-90 TARE (Other)
Arm B
Experimental
TARE then Bevacizumab and Atezolizumab
干预措施: Y-90 TARE (Other)
Arm B
Experimental
TARE then Bevacizumab and Atezolizumab
干预措施: Atezolizumab (Drug)
Arm B
Experimental
TARE then Bevacizumab and Atezolizumab
干预措施: Bevacizumab (Drug)
结局指标
主要结局
Progression Free Survival (PFS) by RECIST 1.1
时间窗: Up to a maximum of 16 months.
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. PFS is defined as time from registration until disease progression met by RECIST 1.1 or death from any cause.
次要结局
- Time to Progression (TTP) by RECIST1.1(Up to a maximum of 16 months.)
- Adverse Events(14 months)
- Progression Free Survival by mRECIST(Up to a maximum of 16 months.)
- Overall Response Rate (ORR) by mRECIST(Up to a maximum of 16 months)
- Time to Progression (TTP) by mRECIST(Up to a maximum of 16 months.)
- Overall Survival (OS)(Upto a maximum of 18 months)
- Subject Function(16 months)
- Overall Response Rate (ORR) by RECIST1.1(Up to a maximum of 16 months)
研究者
Aiwu Ruth He, MD
Sponsor-Investigator
Hoosier Cancer Research Network
研究点 (6)
Loading locations...
相似试验
已完成
2 期
A Study of Atezolizumab and Trastuzumab in Combination With Capecitabine and Oxaliplatin in Patients With HER2 Positive Locally Advanced Resectable Gastric Cancer of Adenocarcinoma of Gastroesophageal JunctionGastroesophageal Junction AdenocarcinomaGastric CancerNCT04661150Hoffmann-La Roche42
已完成
2 期
Atezolizumab Plus Bevacizumab in First Line NSCLC PatientsNon Small Cell Lung CancerNCT03836066Fundación GECP41
已完成
2 期
Atezolizumab and Tiragolumab in Patients With NSCLC or Advanced Solid Tumors Having Had Prior Treatment With a PD-1 InhibitorSolid TumorNon-Small Cell Lung CancerNCT03977467SCRI Development Innovations, LLC46
进行中（未招募）
2 期
Atezolizumab Versus Atezolizumab Plus Bevacizumab as First Line in NSCLC Patients (BEAT)Non-small-cell Lung Cancer PatientsNCT03896074Fondazione Ricerca Traslazionale206
已完成
2 期
A Study of Atezolizumab (an Engineered Anti-Programmed Death-Ligand 1 [PD-L1] Antibody) as Monotherapy or in Combination With Bevacizumab (Avastin®) Compared to Sunitinib (Sutent®) in Participants With Untreated Advanced Renal Cell CarcinomaRenal Cell CarcinomaNCT01984242Hoffmann-La Roche305