Transarterial Chemoembolization in Combination With Nivolumab Performed for Intermediate Stage Hepatocellular Carcinoma (IMMUTACE)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03572582|
Recruitment Status : Recruiting
First Posted : June 28, 2018
Last Update Posted : June 28, 2018
|Condition or disease||Intervention/treatment||Phase|
|Carcinoma, Hepatocellular Hepatic Carcinoma Hepatocellular Cancer||Drug: Nivolumab Drug: TACE||Phase 2|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||49 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Single-arm, Open-label Study of Transarterial Chemoembolization (TACE) in Combination With Nivolumab Performed for Intermediate Stage Hepatocellular Carcinoma (HCC)|
|Actual Study Start Date :||June 14, 2018|
|Estimated Primary Completion Date :||December 2021|
|Estimated Study Completion Date :||September 2022|
Experimental: TACE in combination with 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.
Nivolumab therapy combined with standard TACE treatment
TACE is performed by using drug eluting beads
- Objective Response Rate (ORR) [ Time Frame: Observation period max 42 months ]Objective Response Rate according to modified RECIST for HCC
- Progression Free Survival (PFS) [ Time Frame: 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) [ Time Frame: 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.
- Overall survival (OS) [ Time Frame: max 42 months ]Overall survival is defined as the time from first TACE until death.
- Duration of Response (OR) [ Time Frame: 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.
- Objective Response Rate according to RECIST 1.1 [ Time Frame: max 42 months ]A secondary objective is to estimate best ORR according to RECIST 1.1.
- Time to Failure of Strategy (TTFS) [ Time Frame: 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) [ Time Frame: 36 moths ]EORTC-QLQ-C30 (European Organisation for Research and Treatment of Cancer - Quality of Life Core Questionnaire 30 items) Version 3.0. The QLQ-C30 is composed of multi-item scales and single-item measures, including five functional scales, three symptom scales, a global health Status / QoL scale, and six single items. All of the scales and single-item measures have a score range from 0 to 100. A high score shows a high response level. A high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems functional scales, three symptom scales, a global health status / QoL scale, and six single items.
- Quality of Life (QoL) [ Time Frame: 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) [ Time Frame: 42 months ]Data will be obtained on vital signs, clinical parameters and feasibility of the regimen
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03572582
|Contact: Sonja Schiess, Dr.||+49 (0)30 8145344 ext 42||Sonja.Schiess@aio-studien-ggmbh.de|
|Contact: Katrin Krause||+49 (0)30 8145344 ext 32||Katrin.Krause@aio-studien-ggmbh.de|
|Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie & Endokrinologie||Recruiting|
|Hannover, Germany, 30625|
|Contact: Arndt Vogel, Prof.Dr. Vogel.Arndt@mh-hannover.de|
|Principal Investigator:||Arndt Vogel, Prof.Dr.||Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie & Endokrinologie|