Randomized, Double-Blind, Parallel, Controlled, Multicenter Study of Transarterial Chemoembolization (TACE) Plus ABCB1 Inhibition Versus TACE Alone in Patients With Hepatocellular Carcinoma: IMPACT-TACE
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 152
- 试验地点
- 5
- 主要终点
- complete response rate (CRR)
研究概览
简要总结
IMPACT-TACE is an investigator-initiated, prospective, multicenter, randomized, double-blinded, interventional trial to test the hypothesis that the simultaneous application of doxorubicin with the ABCB1 inhibitor nicardipine would significantly improve the success rate of TACE treatment.
详细描述
Liver cancer, also known as hepatocellular carcinoma (HCC), is the sixth most common tumor disease worldwide. It is an aggressive cancer that is very often fatal, as it is usually detected at a late stage when surgery is no longer possible. International guidelines recommend transarterial chemoembolization (TACE) as the treatment of choice in such cases, as this therapy can prolong survival. In such cases, international guidelines recommend transarterial chemoembolization (TACE) as the treatment of choice, as this therapy can prolong survival. TACE is a widely used interventional method in which a thin catheter is advanced to the liver artery supplying the tumor. Tiny beads loaded with a chemotherapeutic agent (doxorubicin) are then injected directly into the tumor nodules. The beads block the artery supplying the tumor, interrupting the blood supply to the tumor and causing it to die. In addition, the beads slowly release the chemotherapy drug doxorubicin into the tumor, which is intended to contribute to the complete death of the tumor cells. However, the studies also showed that complete death of the tumor node could only be achieved in approximately 25% of patients. The latest study results have revealed that one of the main causes of the incomplete response to TACE therapy is that cancer cells develop resistance to protect themselves against the chemotherapy drug doxorubicin. This resistance can be circumvented by inhibiting the enzyme ABCB1, allowing the chemotherapy drug to act on the tumor cells and kill them completely. The blood pressure medication nicardipine has a strong inhibitory effect on this enzyme. In this study, the investigators therefore want to investigate whether the response to TACE therapy can be improved by administering beads that release the active ingredient nicardipine in the tumor in addition to the chemotherapy drug doxorubicin, so that the tumor nodule cannot develop resistance and dies completely.
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
- •Informed consent as documented by signature,
- •Age ≥18 years,
- •Diagnosis of HCC by biopsy or by established imaging criteria using CT or MRI,
- •At least one target lesion without prior treatment,
- •Diameter of the target lesion ≥3 cm and ≤8 cm,
- •Preserved liver function (no jaundice, no ascites, no overt hepatic encephalopathy).
- •For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods for at least 3 months after the TACE treatment.
排除标准
- •Any prior systemic therapy for advanced HCC,
- •Diffuse tumor lesions, extrahepatic metastases, or vascular invasion,
- •Hepatic encephalopathy,
- •Uncontrolled ascites or pleural effusion,
- •Jaundice,
- •Severe hypotension or hemodynamic shock or need of vasoactive medications,
- •Decompensated heart failure New York Heart Association (NYHA) class IV,
- •eGFR < 15 mL/min/1.73 m2 per MDRD (Modification of Diet in Renal Disease) formula,
- •Myocardial infarction within the last 6 months,
- •Life expectancy <12 weeks,
- •Contraindications to the class of drugs under study, e.g., known hypersensitivity or allergy to calcium antagonists,
- •Inability to follow the procedures of the study, e.g., due to language problems, psychological disorders, dementia, etc. of the participant,
- •Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within at least 3 months after the TACE treatment.
结局指标
主要结局
complete response rate (CRR)
时间窗: 3 month
of the target lesion at time point 3 months after TACE assessed by mRECIST (modified response evaluation criteria in solid tumors) in four-phase CT or contrast MRI according to standard liver imaging protocols
progression-free survival (PFS)
时间窗: up to 12 month
as defined as time to progression of any tumor treated as part of the trial or death of a patient.
次要结局
- Objective response rate (ORR)(3 month)
- Duration of response (DOR)(up to 12 month)
- Change in tumor markers(3 and 6 month)
- Patient-reported outcomes(up to 1 year)
- Overall survival(up to 12 month)
- Complete response of the target lesion(6 month)