Sequential TransArterial Chemoembolization and Stereotactic RadioTherapy Followed by ImmunoTherapy for Downstaging Hepatocellular Carcinoma for Hepatectomy (START-FIT)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 33
- 试验地点
- 1
- 主要终点
- Number of Patients Amendable to Curative Surgical Interventions
研究概览
简要总结
This study is a prospective phase II, single arm clinical study conducted in Queen Mary Hospital (Hong Kong) assessing the efficacy and safety of the sequential administration of trans-arterial chemo-embolization (TACE) and stereotactic body radiotherapy (SBRT) with an immune checkpoint inhibitor in hepatocellular carcinoma (HCC) patients.
详细描述
All the patients must be registered with the Investigator(s) prior to initiation of treatment. The registration desk will confirm all eligibility criteria and obtain essential information (including patient number).
TACE should start within 28 days of study registration and its procedure will be standardised.
SBRT screening and planning will be performed by radiation therapists, medical physicists, and oncologists.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of HCC confirmed pathologically or made according to American Association for the Study of Liver Diseases (AASLD) practice guideline 2010: patients with cirrhosis of any etiology and patients with chronic hepatitis B (HBV) who may not have fully developed cirrhosis, the presence of liver nodule >1cm and demonstrated in a single contrast-enhanced dynamic imaging [magnetic resonance imaging (MRI)] of intense arterial uptake and "washout" in portal venous and delayed phases.
- •Male or female subjects with age: 18-75 years old
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
- •Tumor size 5-15cm or number of lesions ≤3 or segmental portal vein involvement
- •Child-Pugh liver function class A-B7
- •Liver volume minus intrahepatic GTV >700 cc.
- •Minimal distance from GTV to stomach, duodenum, small or large bowel >1 cm.
- •No prior systemic therapy nor immunotherapy
- •No prior trans-arterial chemo-embolization (TACE)
- •No prior radiotherapy to the liver or selective internal radiation (SIRT)
- •Written informed consent obtained for clinical trial participation and providing archival tumor tissue, if available.
- •Subjects with confirmed concomitant HBV infection (defined as HBsAg positive or HBV DNA detectable) that are eligible for inclusion must be treated with antiviral therapy (per local institutional practice) prior to enrollment to ensure adequate viral suppression (HBV DNA <2000 IU/mL), must remain on antiviral therapy for the study duration, and continue therapy for 6 months after the last dose of investigational product(s)
- •At least one measurable lesion according to RECIST v1.
- •Adequate organ and marrow function, as defined below:
- •Hemoglobin ≥9 g/dL
- •Absolute neutrophil count ≥1,500/μL
- •Platelet count ≥100,000/μL
- •Total bilirubin ≤2.0 × ULN
- •ALT ≤3 × ULN
- •Albumin ≥2.8 g/dL
- •Calculated creatinine clearance ≥45 mL/minute as determined by Cockcroft-Gault (using actual body weight) or 24-hour urine creatinine clearance
- •Females of childbearing potential or non-sterilized male who are sexually active must use a highly effective method of contraception
- •Females of childbearing potential must have negative serum or urine pregnancy test
排除标准
- •Prior invasive malignancy within 2 years except for noninvasive malignancies such as cervical carcinoma in situ, in situ prostate cancer, non-melanomatous carcinoma of the skin, lobular or ductal carcinoma in situ of the breast that has been surgically cured
- •Contraindicated of SBRT: Any one hepatocellular carcinoma >15 cm; Total maximal sum of hepatocellular carcinoma >20 cm; More than 3 discrete hepatic nodule; Direct tumor extension into the stomach, duodenum, small bowel, large bowel, common or main branch of biliary tree
- •Severe, active co-morbidity
- •Presence of extra-hepatic metastases (M1)
- •Left portal vein, right portal vein, main portal vein or inferior vena cava (IVC) thrombosis or involvement
- •Presence of clinically meaningful ascites as ascites requiring non pharmacologic intervention (eg, paracentesis) or escalation in pharmacologic intervention to maintain symptomatic control
- •Hepatic encephalopathy
- •Active or untreated gastrointestinal varices
- •Untreated central nervous system (CNS) metastatic disease, lepto-meningeal disease, or cord compression
- •Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke ( <6 months prior to enrollment), myocardial infarction ( <6 months prior to enrollment), unstable angina, congestive heart failure (>= New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
- •Prior treatment with any immune checkpoint inhibitors or an antibody targeting immuno-regulatory receptors or mechanisms
- •Irritable bowel syndrome or other serious gastrointestinal chronic conditions associated with diarrhea within the past 3 years prior to the start of treatment
- •Known history of testing positive for HIV or known acquired immunodeficiency syndrome.
- •On chronic systemic steroid or any other forms of immunosuppressive medication within 14 days prior to the treatment. Except:
- •intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection);
- •Systemic corticosteroids at physiologic doses <=10 mg/day of prednisone or equivalent;
- •Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
- •Active or prior documented autoimmune or inflammatory disorders in the past 2 years, except diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment
- •History of primary immunodeficiency or solid organ transplantation
- •Receipt of live, attenuated vaccine within 28 days prior to the study treatment
- •Active infection requiring systemic therapy
- •Severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb)
- •Females who are pregnant, lactating, or intend to become pregnant during their participation in the study
- •Psychiatric disorders and substance (drug/alcohol) abuse
研究组 & 干预措施
START-FIT
Single group assignment combining TACE and SBRT with immune checkpoint inhibitor as treatment in HCC patients.
Procedure of TACE will be standardized.
SBRT screening and planning will be performed by radiation therapists, medical physicists, and oncologists.
An immune checkpoint inhibitor may be administered up to 3 days before or after the scheduled day of administration of each cycle due to administrative reasons.
干预措施: TACE (Procedure)
START-FIT
Single group assignment combining TACE and SBRT with immune checkpoint inhibitor as treatment in HCC patients.
Procedure of TACE will be standardized.
SBRT screening and planning will be performed by radiation therapists, medical physicists, and oncologists.
An immune checkpoint inhibitor may be administered up to 3 days before or after the scheduled day of administration of each cycle due to administrative reasons.
干预措施: SBRT (Radiation)
START-FIT
Single group assignment combining TACE and SBRT with immune checkpoint inhibitor as treatment in HCC patients.
Procedure of TACE will be standardized.
SBRT screening and planning will be performed by radiation therapists, medical physicists, and oncologists.
An immune checkpoint inhibitor may be administered up to 3 days before or after the scheduled day of administration of each cycle due to administrative reasons.
干预措施: Immune Checkpoint Inhibitor (Drug)
结局指标
主要结局
Number of Patients Amendable to Curative Surgical Interventions
时间窗: from the date of first study treatment to the date of last study treatment, an average of 3 years
Number of patients amendable to curative surgical interventions defined as number of patients receiving curative surgical resection or transplantation after successful down-sizing of tumor(s) by intervention.
次要结局
- Response rate measured by mRECIST criteria(from the date of screening to radiographically documented progression according to mRECIST 1.1, assessed up to 3 years)
- Time to progression (TTP)(from the date of first study treatment to radiographically documented progression according to mRECIST 1.1, assessed up to 3 years)
- Progression-free survival (PFS)(from the date of first study treatment to radiographically documented progression according to mRECIST 1.1 or death from any cause, whichever occurs first, assessed up to 3 years)
- Overall survival (OS)(from the date of first study treatment to the date of death from any cause, assessed up to 5 years)
- European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC-QLQ-C30) Score(from the date of screening to radiographically documented progression according to mRECIST 1.1, an average of 3 years)
- Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) Score(from the date of screening to radiographically documented progression according to mRECIST 1.1, an average of 3 years)
- Incidence of Study-Related Adverse Events [Safety and Tolerability](from the date of screening to 90 days after last treatment, around 3 years and 90 days)
- Pathological response(from the date of first study treatment to radiographically documented progression according to mRECIST 1.1 or death from any cause, whichever occurs first, assessed up to 5 years)
- Disease control rate(from the date of first study treatment to radiographically documented response according to mRECIST 1.1, assessed up to 3 years)
- Local control(from the date of first study treatment to radiographically documented in-field progression according to mRECIST 1.1, censored at the time of intervention to target lesion, assessed up to 3 years)
- Duration of response(from the date of first documented evidence of CR or PR to first documented sign of PD or death from any cause according to mRECIST 1.1, assessed up to 3 years)
- Pattern of failure(from the date of first study treatment to radiographically documented failure type according to mRECIST 1.1, assessed up to 3 years)
研究者
Dr. Chi-Leung Chiang
Clinical Assistant Professor
The University of Hong Kong