Prospective Phase 2 Trial of Yttrium-90 Radiation Segmentectomy for Unresectable Hepatocellular Carcinoma
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR) by mRECIST
研究概览
简要总结
This is a prospective, single-blinded, single-arm, open-label Phase II trial of trans-arterial radiation segmentectomy using Yttrium-90 glass microspheres (TheraSphere®) for Hepatocellular Carcinoma (HCC) participants with unresectable Barcelona clinic liver cancer (BCLC) stage A disease.
详细描述
PRIMARY OBJECTIVES:
I. To evaluate the objective response rate (ORR) after radiation segmentectomy in participants with BCLC Stage A HCC and 1) a single solitary tumor measuring 2-5 centimeters (cm) and 2) 2 or 3 lesions each ≤ 3 cm.
II. To assess the safety of radiation segmentectomy.
SECONDARY OBJECTIVES:
I. To evaluate transplant-free survival.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 22 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must have histologically or imaging-confirmed confirmed HCC.
- •Group 1: Solitary tumor measuring 2-5 cm Or Group 2: 2-3 tumors each ≤ 3 cm in diameter.
- •No prior therapy to target tumor(s).
- •Not a candidate for surgical resection or thermal ablation after multidisciplinary assessment.
- •Age ≥22 years.
- •Eastern Cooperative Oncology Group (ECOG) performance status = 0 or
- •Demonstrated adequate organ function as defined below:
- •Total bilirubin ≤3.0 mg/dL, unless elevated due to Gilbert's syndrome and direct bilirubin is within normal limits.
- •aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) ≤5 X institutional upper limit of normal.
- •alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) ≤5 X institutional upper limit of normal.
- •Creatinine Glomerular filtration rate (GFR) > 30 ml/min.
- •Child-Pugh score ≤ B7
- •Albumin-bilirubin (ALBI) score 1-2
- •Participants who have received systemic therapy for HCC will be excluded from the trial.
- •Ability to understand a written informed consent document, and the willingness to sign it.
- •Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
- •Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
排除标准
- •Macrovascular tumor invasion or infiltrative appearance of hepatocellular carcinoma.
- •History of severe allergy to iodinated contrast agents despite appropriate premedication.
- •Is currently receiving any other anti-cancer agents and any previous therapy with a device that uses Y90 as the radioisotope.
- •Symptomatic heart failure or severe valvular insufficiency.
- •Symptomatic pulmonary hypertension or lung disease.
- •Symptomatic ascites.
- •Severe uncontrolled coagulopathy International Normalized Ratio (INR) ≥ 3.0 or Platelet ≤ 20,
- •Main vein thrombosis (portal vein, both bland and tumor thrombus). Note: Less than lobar portal vein thrombosis is allowable only if the thrombus is bland.
- •Pregnant women are excluded from this study because TheraSphere emits radiation with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with TheraSphere, breastfeeding should be discontinued if the mother is treated with TheraSphere.
- •Lung-shunt fraction (LSF) resulting in anticipated lung dose of >30 Gray (Gy).
- •History of sphincterotomy, biliary-enteric anastomosis, or other biliary tract instrumentation. Note: Prior cholecystectomy with or without bile duct exploration is permitted.
- •Tumor perfused by extrahepatic collateral arteries.
- •Prior partial hepatectomy.
- •Psychiatric illness, other significant medical illness, or social situation which, in the investigator's opinion, would limit compliance or ability to comply with study requirements.
- •History of or current extrahepatic cancer.
- •Pulmonary insufficiency (defined by an arterial oxygen pressure (Pa,O2) of < 60 mmHg, or oxygen saturation (Sa,O2) of < 90%).
研究组 & 干预措施
Group 1. TheraSphere® Yttrium-90 microspheres
Participants with a single tumor measuring 2-5 cm will receive one dose of TheraSphere® >250 Gy, and ideally > 400 Gy at the treating physician's discretion. Participants will be monitored for safety and complete quality of life questionnaires.
干预措施: TheraSphere® Yttrium-90 microspheres (Device)
Group 1. TheraSphere® Yttrium-90 microspheres
Participants with a single tumor measuring 2-5 cm will receive one dose of TheraSphere® >250 Gy, and ideally > 400 Gy at the treating physician's discretion. Participants will be monitored for safety and complete quality of life questionnaires.
干预措施: Health Related Quality of Life Questionnaires (HRQOL) (Other)
Group 2. TheraSphere® Yttrium-90 microspheres
Participants with 2-3 tumors ≤ 3 cm in diameter (T2 disease) will receive one dose of TheraSphere® >250 Gy, and ideally > 400 Gy at the treating physician's discretion. Participants will be monitored for safety and complete quality of life questionnaires.
干预措施: TheraSphere® Yttrium-90 microspheres (Device)
Group 2. TheraSphere® Yttrium-90 microspheres
Participants with 2-3 tumors ≤ 3 cm in diameter (T2 disease) will receive one dose of TheraSphere® >250 Gy, and ideally > 400 Gy at the treating physician's discretion. Participants will be monitored for safety and complete quality of life questionnaires.
干预措施: Health Related Quality of Life Questionnaires (HRQOL) (Other)
结局指标
主要结局
Objective Response Rate (ORR) by mRECIST
时间窗: Up to 6 months
The objective response rate (ORR) after radiation segmentectomy in participants will be evaluated using a modified Response Evaluation Criteria in Solid Tumors (mRECIST) based on the best tumor response where Complete Response (CR) is defined as the disappearance of any intratumoral arterial enhancement in all target lesions, Partial Response (PR) is defined as a 30% decrease in the sum of diameters of viable (enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions, Stable Disease (SD) is defined as any cases that do not qualify for either partial response or progressive disease, and Progressive Disease (PD) is defined as an increase of at least 20% in the sum of the diameters of viable (enhancing) target lesions, taking as reference the smallest sum of the diameters of viable (enhancing) target lesions recorded since treatment started.
Percentage of participants with treatment-related adverse events
时间窗: Up to 6 months
The percentage of participants with grade 3 or greater, treatment-related adverse events as classified by NCI Common Terminology Criteria for Adverse Events (CTCAE) will be reported.
次要结局
- Median time from TheraSphere administration to transplant(Up to 3 years)
- Median time to disease progression(Up to 3 years)
- Changes in mean Functional Assessment of Cancer Therapy - Hepatobiliary (FACT-Hep) survey results over time(Up to 6 months)
- Changes in mean EuroQol five-dimensional Questionnaire (EQ-5D) survey results over time(Up to 6 months)
- Best observed tumor response by mRECIST.(Up to 1 year)
- Proportion of participants on an active liver transplant waitlist who receive a transplant(Up to 3 years)
- Proportion of participants requiring additional therapies(Up to 3 years)
- Proportion of participants with Complete pathologic response (CPN)(Up to 3 years)
研究者
R. Peter Lokken, MD, MPH
Associate Professor of Clinical Radiology
University of California, San Francisco