NCT03572582

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
49

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Jun 2018

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 29, 2018

Completed
16 days until next milestone

Study Start

First participant enrolled

June 14, 2018

Completed
14 days until next milestone

First Posted

Study publicly available on registry

June 28, 2018

Completed
3.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 12, 2021

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 10, 2021

Completed
Last Updated

July 20, 2023

Status Verified

July 1, 2023

Enrollment Period

3.3 years

First QC Date

May 29, 2018

Last Update Submit

July 19, 2023

Conditions

Carcinoma, HepatocellularHepatic CarcinomaHepatocellular Cancer

Outcome Measures

Primary Outcomes (1)

  • Objective Response Rate (ORR)

    Objective Response Rate according to modified RECIST for HCC

    Observation period max 42 months

Secondary Outcomes (9)

  • Progression Free Survival (PFS)

    max 42 months

  • Time to Progression (TTP)

    max 42 months

  • Overall survival (OS)

    max 42 months

  • Duration of Response (OR)

    max 42 months

  • Objective Response Rate according to RECIST 1.1

    max 42 months

  • +4 more secondary outcomes

Study Arms (1)

TACE in combination with nivolumab

EXPERIMENTAL

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.

Drug: NivolumabDrug: TACE

Interventions

NivolumabDRUG

Nivolumab therapy combined with standard TACE treatment

TACE in combination with nivolumab
TACEDRUG

TACE is performed by using drug eluting beads

TACE in combination with nivolumab

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Written informed consent including participation in translational research and any locally-required authorization (EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations.
  • Age ≥ 18 years at time of study entry
  • Multinodular or large, solitary HCC, not eligible for resection or local ablation, Tumor burden below 50% of liver volume.
  • Histologically confirmed diagnosis of HCC.
  • At least one measurable site of disease as defined by modified RECIST (mRECIST) criteria with spiral CT scan or MRI.
  • Child-Pugh A, performance status (PS) ≤ 2 (ECOG scale).
  • Subjects with chronic HBV infection must have HBV DNA viral load \< 100 IU/mL at screening. In addition, they must be on antiviral therapy per regional standard of care guidelines prior to initiation of study therapy.
  • Life expectancy of at least 12 weeks.
  • Adequate blood count, liver-enzymes, and renal function: Haemoglobin ≥ 8.5 g/dL, absolute neutrophil count ≥ 1,500/L, platelets ≥70 x103/L; Total bilirubin ≤ 3x upper normal limit; Aspartate Aminotransferase (SGOT), Alanine aminotransferase (SGPT) ≤ 5 x upper normal limit (ULN); International normalized ratio (INR) ≤1.25; Albumin ≥ 31 g/dL; Serum Creatinine ≤ 1.5 x institutional ULN or creatinine clearance (CrCl) ≥ 30 mL/min (if using the Cockcroft-Gault formula )
  • Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial.
  • Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment, adherence to contraceptive measures, scheduled visits and examinations including follow up.

You may not qualify if:

  • Methodological or clinical criteria:
  • Diffuse HCC or presence of vascular invasion or extrahepatic spread with the following exceptions:
  • Invasion of a segmental portal vein or hepatic veins
  • Limited extrahepatic metastases with one organ system manifestations, e.g. lymphnodal, pulmonary, ossary metastases. For lymphnodal metastases Maximum three metastases, maximum 2 cm in the longest diameter, and for all other metastases only solitary metastases, maximum 2 cm in the longest diameter, are allowed.
  • Patients on a liver transplantation list or with advanced liver disease as defined below:
  • Encephalopathy;
  • Untreatable ascites.
  • Any contraindications for hepatic embolization procedures:
  • Known hepatofugal blood flow;
  • Known porto-systemic shunt;
  • Impaired clotting test (platelet count \<70 x103/L, INR \>1.25);
  • Renal failure/ insufficiency requiring hemo-or peritoneal dialysis;
  • Known severe atheromatosis;
  • Total thrombosis or total invasion of the main branch of the portal vein.
  • History of cardiac disease:
  • +37 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie & Endokrinologie

Hanover, 30625, Germany

Location

Related Publications (1)

  • Kloeckner R, Galle PR, Bruix J. Local and Regional Therapies for Hepatocellular Carcinoma. Hepatology. 2021 Jan;73 Suppl 1:137-149. doi: 10.1002/hep.31424. Epub 2020 Nov 6. No abstract available.

    PMID: 32557715DERIVED

Related Links

MeSH Terms

Conditions

Carcinoma, HepatocellularLiver Neoplasms

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsDigestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesLiver Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Arndt Vogel, Prof.Dr.

    Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie & Endokrinologie

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 29, 2018

First Posted

June 28, 2018

Study Start

June 14, 2018

Primary Completion

October 12, 2021

Study Completion

December 10, 2021

Last Updated

July 20, 2023

Record last verified: 2023-07

Data Sharing

IPD Sharing
Will not share

Locations

DE(1)