Neoplasms

All Conditions

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Immunomodulating Agents

Chlorotrianisene

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

* Pembrolizumab 200mg IV Q3W on day 1 of cycle 1 and 2
* Radio Frequency Ablation (RFA) / Microwave Ablation (MWA) / brachytherapy or combination of TACE with RFA, MWA or brachytherapy will be performed on day 1 of cycle 3
* Pembrolizumab 200mg IV administration 2 days after local ablation
* Pembrolizumab 200mg IV Q3W for up to 12 months total treatment duration

Local ablation via RFA will be performed via ultrasound- or CT-guided placement of a needle electrode / probe penetrating into the lesion center

Radio Frequency Ablation (RFA)

Local ablation via MWA will be performed via ultrasound- or CT-guided placement of a needle electrode / probe penetrating into the lesion center

Microwave Ablation (MWA)

Local ablation via brachythwerapy will be performed via ultrasound- or CT-guided placement of a needle electrode / probe penetrating into the lesion center

Brachytherapy

According to Investigator's choice, TACE using drug eluting beads can be performed combined with RFA, MWA or brachytherapy

Transarterial Chemoembolisation (TACE)

Salah-Eddin Al-Batran, Prof. Dr.

This is a multicenter, single arm, prospective, open-label phase II trial investigating the clinical activity of peri-interventional treatment with the anti-PD1 antibody pembrolizumab in HCC patients who are candidates for local ablation via either radiofrequency ablation (RFA) or microwave ablation (MWA) or brachytherapy or combination of TACE with RFA, MWA or brachytherapy.

The multimodal approach of combining peri-interventional administration of an immune checkpoint inhibitor and local ablation via RFA / MWA / brachytherapy or combination of TACE with RFA, MWA or brachytherapy harbors the potential to satisfy the unmet need for an improvement in the outcomes of HCC patients treated with RFA / MWA/ brachytherapy or combination of TACE with RFA, MWA or brachytherapy. Furthermore, early clinical data indicates that the combination of immune checkpoint inhibition with RFA, MWA or brachytherapy displays an acceptable safety profile, resulting in a positive benefit-risk ratio of this trial.

Immunotherapy with pembrolizumab in combination with local ablation

IMMULAB - Immunotherapy With Pembrolizumab in Combination With Local Ablation in Hepatocellular Carcinoma (HCC)

IMMULAB - A Phase II Trial of Immunotherapy With Pembrolizumab in Combination With Local Ablation for Patients With Early Stage Hepatocellular Carcinoma (HCC)

Evaluation of ORR according to RECIST 1.1 after two cycles of pembrolizumab and before performing local ablation will allow testing of the hypothesis that pre-interventional treatment with pembrolizumab before local ablation will result in conversion / downstaging of borderline candidates for local ablation. Furthermore, ORR is generally accepted as a valid endpoint for efficacy evaluation in one-armed trials without control group.

TTR and recurrence free survival, have meanwhile been accepted by medicinal agencies in drug approval processes as they allow for quicker efficacy assessment. This is most important in explorative clinical trials in early phases (like this phase II trial) as it allows for more rapid evaluation of the potential of new treatment approaches. Furthermore, many of these parameters are not influenced by follow-up therapies.

Overall survival will be evaluated and is still considered the gold standard for efficacy evaluation in clinical trials. Its major drawback is the potentially long observation period necessary for OS evaluation - especially in the curative setting as represented by the treatment approach in this trial.

Incidence and severity of adverse events according to the current National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)

Correlation analyses between selected molecular parameters and clinical data to identify molecular biomarkers like PD-1, PD-L1 and PD-L2) and immune cell infiltrates (like e.g. IGHM, CD3, CD8, FOXP3, CD68, CD205) as well as chemokines (CXCL9. CXCL10, CXCL13) and invasion markers (MMP7, MMP9) in tumor tissue and blood samples predictive for ORR, TTR, recurrence free survival and OS. Analyses will be performed by immunohistochemical and molecular methods in a central lab.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
IMMULAB - Immunotherapy With Pembrolizumab in Combination With Local Ablation in Hepatocellular Carcinoma (HCC)	NCT03753659	Hepatocellular ...	Pembrolizumab Radio Frequency... Microwave Ablat... Brachytherapy Transarterial C...	18 Years -	Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
IMMULAB - Immunotherapy With Pembrolizumab in Combination With Local Ablation in Hepatocellular Carcinoma (HCC)	NCT03753659	Hepatocellular ...	Pembrolizumab Radio Frequency... Microwave Ablat... Brachytherapy Transarterial C...	18 Years -	Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

Spots Global Cancer Trial Database for radio frequency ablation (rfa)