Transarterial Chemoembolization (TACE) Plus ABCB1 Inhibition Versus TACE Alone in Patients With Hepatocellular Carcinoma

Official title

Randomized, Double-Blind, Parallel, Controlled, Multicenter Study of Transarterial Chemoembolization (TACE) Plus ABCB1 Inhibition Versus TACE Alone in Patients With Hepatocellular Carcinoma: IMPACT-TACE

Overview

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.

Detailed description

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.

Interventions

• Combination product DEB-DoxNic-TACE
  TACE (transarterial chemoembolization) with 1-3 mL drug-eluting beads (DEB) loaded with 33mg/ml doxorubicin (Dox) and 0.3mg/mL nicardipine (Nic)
• Combination product current standard of care
  TACE (transarterial chemoembolization) with 1-3 mL drug-eluting beads loaded with 33mg/ml doxorubicin

Primary outcome measures

• complete response rate (CRR) [Time frame: 3 month]
• progression-free survival (PFS) [Time frame: up to 12 month]

Secondary outcome measures (6)

• Objective response rate (ORR) [Time frame: 3 month]
• Duration of response (DOR) [Time frame: up to 12 month]
• Change in tumor markers [Time frame: 3 and 6 month]
• Patient-reported outcomes [Time frame: up to 1 year]
• Overall survival [Time frame: up to 12 month]
• Complete response of the target lesion [Time frame: 6 month]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Switzerland · 3 centers

• University Hospital Basel — Basel
• Hôpitaux Universitaires de Genève — Geneva
• Kantonsspital St. Gallen — Sankt Gallen

Identifiers

NCT: NCT07302919 · 2024-02072, bb24heim

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗