A Multicenter Clinical Study of Combined Therapy for Unresectable Hepatocellular Carcinoma
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18-80
SponsorWest China Hospital
About this trial
This clinical trial was designed to evaluate the safety and efficacy of Y90-SIRT combined with nivolumab, ipilimumab, and lenvatinib in patients with unresectable HCC. In addition to assessing short-term efficacy endpoints, such as ORR and PFS, this trial places particular emphasis on the OS benefit for patients. This study is therefore both novel and innovative.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
HCC confirmed as unresectable by imaging or histology, or patients who refuse surgery. Eligible for Y90-SIRT, with no evidence of extrahepatic disease on any available imaging. Lymph node involvement is permitted. The term "unresectable hepatocellular carcinoma" refers to a clinical state in which radical surgical resection is precluded because the tumor extent or an inadequate anticipated future liver remnant would prevent R0 removal, or because the procedural risk is prohibitively high, and where surgical intervention is not expected to yield a survival advantage over non-surgical therapies.
Aged between 18 and 80 years at the time of enrollment
Participants with Child-Pugh class A.
Participants with an ECOG performance status of 0 or 1 at the time of enrollment
Disqualifiers
Diffuse HCC or presence of vascular invasion or extrahepatic spread, with the following exceptions: invasion of segmental portal vein or hepatic vein.
Patients with Child-Pugh class C cirrhosis.
Any contraindication to hepatic arterial embolization: Known hepatic arterial reflux; known portosystemic shunt; coagulopathy (platelet count < 50 × 109/L, INR > 1.5); renal failure/insufficiency requiring hemodialysis or peritoneal dialysis; known severe arteriosclerosis; complete thrombosis or complete invasion of the main portal vein.
History of heart disease: congestive heart failure > New York Heart Association (NYHA) class II; active coronary artery disease (CAD) (myocardial infarction ≥ 6 months prior to study initiation is permitted); arrhythmias that are difficult to control with antiarrhythmic drugs or require a pacemaker (NCI-CTCAE v5.0 > grade 2); uncontrolled hypertension; clinically significant gastrointestinal bleeding within 4 weeks prior to initiation of study drugs.
Trial design
Design model
Single group
Treatments tested in this trial
ttrium-90 microspheres in combination with nivolumab, ipilimumab, and lenvatinib in patients with unresectable hepatocellular carcinoma
DrugThe phase Ib portion of the trial explores the incidence of dose-limiting toxicity (DLT) in the quadruple therapeutic regimen. Three weeks after receiving Y90-SIRT, the patients are assigned to one of three dose exploration cohorts: (1) nivolumab 1 mg/kg IV every 3 weeks (Q3W) + ipilimumab 1 mg/kg IV Q3W for up to 4 cycles; (2) nivolumab 1 mg/kg IV Q3W + ipilimumab 2 mg/kg IV Q3W for up to 4 cycles; (3) nivolumab 1 mg/kg IV Q3W + ipilimumab 3 mg/kg IV Q3W for up to 4 cycles. After completion of ipilimumab administration, nivolumab is continued at 480 mg IV every 4 weeks (Q4W) until disease progression, unacceptable toxicity, withdrawal of informed consent, or a maximum treatment duration of two years. Lenvatinib is then administered after discontinuation of ipilimumab, in combination with nivolumab, at a dose of 8 mg (body weight \<60 kg) or 12 mg (body weight \>60 kg) orally once daily (PO QD), taken at a fixed time each day, with or without food.
Treatment groups
33 Participants
are divided into 1 treatment groupGroup A: Yttrium-90 microspheres in combination with nivolumab, ipilimumab, and lenvatinibExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Incidence of dose-limiting toxicity (DLT) of the quadruple regimen (Y90-SIRT plus nivolumab, ipilimumab, lenvatinib)
Time frame
Up to 4 treatment cycles (each cycle is 3 weeks)2
Objective response rate (ORR) assessed by both iRECIST and mRECIST criteria
Time frame
24 monthsSponsors and contacts
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Source ClinicalTrials.gov