Transarterial Chemoembolization in Combination With Nivolumab Performed for Intermediate Stage Hepatocellular Carcinoma

Phase 2

Completed

• Conditions: Carcinoma, Hepatocellular; Hepatic Carcinoma; Hepatocellular Cancer
• Interventions: Drug: Nivolumab; Drug: TACE

• Registration Number: NCT03572582
• Lead Sponsor: AIO-Studien-gGmbH

Brief Summary

The IMMUTACE study evaluates the safety and the efficacy of the anti-programmed-death-1 antibody (anti-PD-1) nivolumab in combination with transarterial chemoembolization (TACE) in patients with multinodular, intermediate stage hepatocellular carcinoma (HCC) as first line therapy.

Detailed Description

Hepatocellular carcinoma (HCC) is one of the most lethal and prevalent cancers worldwide. The prognosis of patients with HCC is dismal and the mortality rates are almost the same as the incidence rates.

The transarterial chemoembolization (TACE) is commonly used to act locally in the intermediate disease stage and is the most common first-line treatment in patients with HCC. Early randomized trials and more recent reviews and meta-analyses reported improved survival rates of patients with unresectable lesions managed with TACE so that TACE has been accepted as the standard treatment for intermediate stage disease. However, outcome of patients treated with TACE in real-life cohorts is still very poor with median overall survival (OS) of 20 months or less.

In order to increase the outcome of TACE, several trials have analyzed the combination of TACE with sorafenib and other anti-angiogenic agents. However, none of the trials have reported an improved overall survival for patients treated with the combination of TACE and sorafenib. Early clinical data already support a safe combination of immune checkpoint inhibition with TACE. Moreover, preliminary data from the CheckMate-040 trial strongly suggest that nivolumab has clinical activity and is tolerable in patients with HCC, including those with hepatitis B or hepatitis C virus (HCV) infection.

Therefore, the aim of this study is to evaluate the safety and efficacy of TACE in combination with nivolumab in patients with intermediate stage HCC.

Study Timeline

• Study First Submitted: 2018-05-29
• Study Start: 2018-06-14
• Study First Submitted QC: 2018-06-19
• Study First Posted: 2018-06-28
• Primary Completion: 2021-10-12
• Study Completion: 2021-12-10
• Status Verified: 2023-07
• Last Update Submitted: 2023-07-19
• Last Update Posted: 2023-07-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 49

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
TACE in combination with nivolumab	Nivolumab	Treatment will be divided into 4-week cycles from the starting date of TACE. The second TACE will be repeated on day 1 (± 4 days) of cycle 3 (after 8 weeks ± 4 days). Nivolumab will be initiated on day 2-3 after the first TACE session. Nivolumab will be administered every two weeks (240mg fixed dose IV) until disease progression for up to two years.
TACE in combination with nivolumab	TACE	Treatment will be divided into 4-week cycles from the starting date of TACE. The second TACE will be repeated on day 1 (± 4 days) of cycle 3 (after 8 weeks ± 4 days). Nivolumab will be initiated on day 2-3 after the first TACE session. Nivolumab will be administered every two weeks (240mg fixed dose IV) until disease progression for up to two years.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	Observation period max 42 months	Objective Response Rate according to modified RECIST for HCC

Secondary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	max 42 months	Progression according to mRECIST for HCC with the exception of new intrahepatic lesions, which are assessed to be treatable with one additional locoregional therapy. Progression following one additional locoregional treatment of such lesions according to mRECIST would be equivalent to failure of strategy.
Time to Progression (TTP)	max 42 months	It is defined as the time from first TACE to the date of the first documented tumor progression according to the definition above.
Objective Response Rate according to RECIST 1.1	max 42 months	A secondary objective is to estimate best ORR according to RECIST 1.1.
Overall survival (OS)	max 42 months	Overall survival is defined as the time from first TACE until death.
Duration of Response (OR)	max 42 months	It is defined as time between the date of first radiographic documented objective response according to mRECIST for HCC and the date of the radiographic disease progression.
Time to Failure of Strategy (TTFS)	max 42 months	Progression according to mRECIST for HCC with the exception of new intrahepatic lesions, which are assessed to be treatable with one additional locoregional therapy (TACE, radiofrequency ablation \[RFA\] / microwave ablation \[MWA\] or resection)
Quality of Life (QoL)	36 months	EORTC-QLQ-HCC18 (European Organisation for Research and Treatment of Cancer - Quality of Life Core Questionnaire - Hepatocellular carcinoma module 18). The HCC18 module for patients with Hepatocellular carcinoma includes 18 items, conceptualised as consisting of 6 scales and 2 single items, which should always be complemented by the EORTC-QLQ-C30.
Incidence of Treatment Emergent Adverse Events as assessed by NCI CTCAE V4.03 (Safety and Tolerability)	42 months	Data will be obtained on vital signs, clinical parameters and feasibility of the regimen

Trial Locations

Locations (1)

Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie & Endokrinologie; 🇩🇪 Hannover, Germany