A Phase 3, Randomized, Double-Blind Study of Tivantinib (ARQ 197) in Subjects With MET Diagnostic-High Inoperable Hepatocellular Carcinoma Treated With One Prior Systemic Therapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 383
- 主要终点
- Median Overall Survival (OS) Following Treatment With Tivantinib 120 mg BID Compared to Placebo Group in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy
研究概览
简要总结
The purpose of this study is to determine if tivantinib (ARQ 197) is effective in treating patients with MET diagnostic-high hepatocellular carcinoma (liver cancer) who have already been treated once with another therapy.
详细描述
Expression of c-Met in tumors correlates with aggressive hepatocellular carcinoma (HCC) features. Overexpression of the receptor in tumor samples or high level of blood HGF in subjects is related to higher recurrence rate after surgery for HCC, while high c-Met expression correlates with shorter survival in HCC subjects. In summary, c-Met holds an important prognostic role in the natural history of HCC. This Phase 3 study in MET Diagnostic-High inoperable HCC subjects has been designed based on the results from the randomized, controlled Phase 2 study conducted by ArQule, Inc. with tivantinib versus placebo in subjects with MET Diagnostic-High inoperable HCC who have failed one prior systemic therapy, mentioned above. The purpose of this study is to confirm the efficacy of tivantinib in MET Diagnostic-High HCC subjects who were previously treated with one systemic therapy, and to further evaluate the safety profile of the experimental drug in this subject population.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Histologically confirmed HCC that is inoperable (where surgery is not indicated due to disease extension, co-morbidities, or other technical reasons), and not eligible for local therapy
- •MET Diagnostic-High tissue reported by the central authorized laboratory using archival or recent biopsy tumor samples
- •Received at least 4 weeks of one prior sorafenib containing systemic therapy and then experienced documented radiographic disease progression; or inability to tolerate prior therapy received for at least a minimum period of time.
- •Discontinued prior systemic treatment or any investigational drug for at least 2 weeks (14 days) or for at least 3 weeks for IV anti-cancer drugs, prior to the study randomization
- •Local or loco-regional therapy (i.e., surgery, radiation therapy, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation) must have been completed >= 4 weeks prior to randomization
- •Measurable disease as defined by the RECIST v1.1.
排除标准
- •More than 1 prior systemic regimen (prior MET inhibitors/antibodies are not allowed; experimental systemic therapy for inoperable HCC given before or after sorafenib counts as separate regimen and is not allowed)
- •Child-Pugh B-C cirrhotic status based on clinical findings and laboratory results
- •Previous or concurrent cancer that is distinct from HCC in primary site or histology, EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, and superficial bladder tumors. Any cancer curatively treated more than 3 years prior to enrollment is permitted.
- •History of congestive heart failure defined as Class II to IV per New York Heart Association (NYHA) classification within 6 months prior to study entry; active coronary artery disease (CAD); clinically significant bradycardia or other uncontrolled, cardiac arrhythmia defined as greater than or equal to Grade 3 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), or uncontrolled hypertension; myocardial infarction occurring within 6 months prior to study entry (myocardial infarction occurring more than 6 months prior to study entry is permitted)
- •Active clinically serious infections defined as >= Grade 3 according to NCI CTCAE
- •Any medical, psychological, or social conditions, particularly if unstable, including substance abuse, that may, in the opinion of the Investigator, interfere with the subject's safety or participation in the study, protocol compliance, or evaluation of the study results
- •Known human immunodeficiency virus (HIV) infection
- •Blood or albumin transfusion within 5 days prior to the blood draw being used to confirm eligibility
- •Concomitant interferon therapy or therapies for active Hepatitis C virus (HCV) infection
- •Pregnancy or breast-feeding
- •History of liver transplant
- •Inability to swallow oral medications
- •Clinically significant gastrointestinal bleeding occurring <= 4 weeks prior to randomization
- •Pleural effusion or clinically evident (visible or palpable) ascites
研究组 & 干预措施
Tivantinib 240 mg BID Cohort
The tivantinib dosage of 240 mg tablets administered by mouth twice daily (BID), once in the morning and once in the evening, with food, for a total daily dose of 480 mg.
干预措施: Tivantinib (Drug)
Tivantinib 120 mg BID Cohort
Tivantinib 120 mg is administered by oral tablet BID, once in the morning and once in the evening, with food, for a total daily dose of 240 mg (amended dosing group; primary analysis group).
干预措施: Tivantinib (Drug)
Placebo Matching 240 mg BID Cohort
Matching placebo is administered by oral tablet(s) BID, once in the morning and once in the evening, with food.
干预措施: Placebo (Drug)
Placebo Matching 120 mg BID Cohort
Matching placebo is administered by oral tablet(s) BID, once in the morning and once in the evening, with food.
干预措施: Placebo (Drug)
结局指标
主要结局
Median Overall Survival (OS) Following Treatment With Tivantinib 120 mg BID Compared to Placebo Group in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy
时间窗: within 36 months
Overall survival (OS) is defined as the time from randomization to the date of death. The rate of OS (percentage of participants still alive) was determined only in the tivantinib 120 mg BID cohort.
Overall Survival (OS) Rate At Different Time Points Following Treatment With Tivantinib 120 mg BID Compared to Placebo Group in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy
时间窗: within 36 months
Overall survival (OS) is defined as the time from randomization to the date of death. The rate of OS (percentage of participants still alive) was determined only in the tivantinib 120 mg BID cohort.
次要结局
- Progression-free Survival Following Treatment With Tivantinib 120 mg BID Compared to Placebo Group in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy (ITT Population)(within 10 months)
- Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy(Baseline to 30 days after last dose, up to approximately 4 years)