Nivolumab in Combination With TACE for Patients With Intermediate Stage HCC (TACE-3)
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|ClinicalTrials.gov Identifier: NCT04268888|
Recruitment Status : Recruiting
First Posted : February 13, 2020
Last Update Posted : February 13, 2020
|Condition or disease||Intervention/treatment||Phase|
|Hepatocellular Carcinoma||Drug: Nivolumab and TACE Procedure: TACE||Phase 2 Phase 3|
A significant proportion of HCC patients present with, or progress to, intermediate stage disease and these patients are typically treated with transarterial chemo-embolisation (TACE).
However, since TACE is generally a palliative therapy, it provides a potential backbone for the addition of effective systemic therapies with the aim of improving survival outcomes. Since TACE may liberate an abundance of tumour antigens and 'danger' signals, it may lend itself to combination with immunotherapeutic strategies.
Doxorubicin is an anthracycline antibiotic with antineoplastic activity. Doxorubicin, isolated from the bacterium Streptomyces peucetius var. caesius, is the hydroxylated congener of daunorubicin. Doxorubicin intercalates between base pairs in the DNA helix, thereby preventing DNA replication and ultimately inhibiting protein synthesis. Additionally, doxorubicin inhibits topoisomerase II which results in an increased and stabilized cleavable enzyme-DNA linked complex during DNA replication and subsequently prevents the ligation of the nucleotide strand after double-strand breakage. Doxorubicin also forms oxygen free radicals resulting in cytotoxicity secondary to lipid peroxidation of cell membrane lipids; the formation of oxygen free radicals also contributes to the toxicity of the anthracycline antibiotics, namely the cardiac and cutaneous vascular effects.
Nivolumab is a human monoclonal antibody. Nivolumab targets the programmed death-1 PD-1) cluster of differentiation 279 (CD279) cell surface membrane receptor. PD-1 is a negative regulatory molecule expressed by activated T and B lymphocytes.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||522 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Patients shall be randomised on a 1:1 basis throughout the study and allocated using pre-generated lists produced by the study statistician. List shall be produced using permuted blocks algorithm with random block sizes of 2 and 4. Stratification factors used in the study are randomising centre, baseline HAP score (A vs. B vs. C) and vascular invasion (No vs. Yes).|
|Masking:||None (Open Label)|
|Official Title:||A Two-arm Multi-stage (TAMS) Seamless Phase II/III Randomised Trial of Nivolumab in Combination With TACE for Patients With Intermediate Stage HCC|
|Actual Study Start Date :||May 8, 2019|
|Estimated Primary Completion Date :||June 2025|
|Estimated Study Completion Date :||June 2026|
Active Comparator: TACE
Transarterial Chemoembolisation using DC Beads™ (TACE) loaded with doxorubicin ALONE.
TACE (DC Bead loaded with doxorubicin hydrochloride)
Experimental: TACE and Nivolumab
As above for TACE. Nivolumab adminstered as a flat dose of 480mg IV.
Drug: Nivolumab and TACE
Immunotherapy and TACE
TACE (DC Bead loaded with doxorubicin hydrochloride)
- Overall Survival - phase III primary outcome [ Time Frame: The time until death. Patients discontinuing the study, lost to follow-up or still alive at the end of the study will be censored at the last know date alive, this can be assessed up until 2 years after the last patient. ]Measured in days
- Time to TACE Progression (TTTP) - phase II primary outcome [ Time Frame: The time to confirmatory scan 4 weeks after progression this can be assessed up until 2 years after the last patient is randomised ]Measured in days
- Time to Progression [ Time Frame: Time to date of progression confirmed by RECIST1.1 assessed up until 2 years after the last patient is randomised ]Measured in days
- Radiological response rate [ Time Frame: Through study completion ]RECIST 1.1
- Safety and Toxicity: the number and percentage of patients reporting a Serious Adverse Event (SAE) and Grade 3 or higher Adverse Event (AE) [ Time Frame: Through study completion ]the number and percentage of patients reporting a Serious Adverse Event (SAE) and Grade 3 or higher Adverse Event (AE), measured and categorised based on CTCAE (version 4).
- Progression Free Survival [ Time Frame: Time to progression or death. Assessed up until 2 years. ]Measured in days
- QOL: EORTC QLQ-C30 [ Time Frame: baseline, pre - TACE (first treatment) and 12 weekly thereafter until end of treatment. Assessed up until 2 years after the last patient is randomised ]QoL will be scored according to the EORTC QLQ-C30 manual and guidelines.
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): NCT04268888
|Contact: Maria Maguire, PhD||0151 firstname.lastname@example.org|
|Contact: David Price||0151 email@example.com|
|University of Liverpool||Recruiting|
|Liverpool, United Kingdom, L69 7ZB|
|Contact: Louise Handley 0151 794 8935 firstname.lastname@example.org|
|Principal Investigator: Daniel Palmer, PhD, MD|
|Study Director:||Daniel Palmer, PhD, MD||Clatterbridge Cancer Centre|