IMMULAB – A phase II trial of immunotherapy with pembrolizumab in combination with local ablation for patients with early stage hepatocellular carcinoma (HCC)
- Conditions
- early stage hepatocellular carcinoma (HCC)MedDRA version: 20.0Level: PTClassification code 10073071Term: Hepatocellular carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-001381-42-DE
- Lead Sponsor
- Institut für Klinische Krebsforschung IKF GmbH am Krankenhaus Nordwest
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Not Recruiting
- Sex
- All
- Target Recruitment
- 30
1.Histologically confirmed diagnosis of HCC
2.Child-Pugh Classification score = 6 for assessed liver function
3.Candidate for local ablation (via either RFA, MWA, brachytherapy or combination of TACE with RFA, MWA or brachytherapy )
4.Patients (including high risk patients) with.:
•Presence of = 5 tumor nodules with diameters = 7cm [longest axis] each OR
•Vascular infiltration
5.No prior systemic therapy for HCC
NOTE: Patients who have received prior local therapy by transarterial chemoembolization (TACE) are not excluded if TACE has been performed >8 weeks before study allocation.
6.Measurable disease based on RECIST 1.1.
7.Male/female participants who are at least 18 years of age on the day of signing informed consent
8.A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
a.) Not a woman of childbearing potential (WOCBP) as defined in Appendix 3
OR
b.) A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 120 days after the last dose of study treatment.
A male participant with female partner of childbearing potential is eligible to participate if he agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 120 days after the last dose of study treatment.
9.The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
10.Have provided archival tumor tissue sample or newly obtained biopsy of a tumor lesion not previously irradiated for mandatory pre-treatment evaluation (baseline).
•Newly obtained biopsies are preferred to archived tissue (archived specimen =6 months may be acceptable).
•Core or excisional biopsies mandatory (fine needle aspiration and bone metastasis samples are not acceptable).
•Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides.
•If submitting unstained cut slides, newly cut slides should be submitted to the central pathology lab within 14 days from the date slides are cut.
•Availability of baseline tumor biopsy samples has to be ensured by site before first dose of study medication is administered.
•Specimens have to be sent to central pathology lab for accompanying research project.
11.Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the date of allocation/randomization.
12.Have adequate organ function as defined in the following table.
13.If patient has concurrent Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection, meets the following criteria:
-Patients with HBV or HCV infection should be monitored for viral levels during study participation.
-Patients with detectable hepatitis B surface antigen (HBsAg) or detectable HBV DNA should be managed per local treatment guidelines.
Controlled (treated) hepatitis B subjects will be allowed if they started treatment at the time point of enrollment into the study by the latest and treatment is continued during study participation.
-Patients with detectable HCV RNA are usually not treated for their HCV infection. However, patients treated for HCV are considered suitable for inclusion if antiviral therapy has been completed = 30 days prior to first administration of study drug.
Are the trial subjects under 18? no
Number of subjects for this age range
1.Extrahepatic disease
2.Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
3.Presence of tumor thrombus involving main trunk of portal vein
4.Has at Screening and/or has had any prior history of Grade = 2 hepatic encephalopathy
5.Has at Screening pericardial effusion, uncontrollable pleural effusion, or clinically significant ascites defined as meeting either of (a) detectable ascites on Screening physical examination OR (b) has at Screening ascites requiring paracentesis
6.A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
7.Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
8.Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks or at least 5 half-lives of the respective drug/IMP (whichever is longer) prior to allocation.
Note: Participants must have recovered from all AEs due to previous therapies to =Grade 1 or baseline. Participants with =Grade 2 neuropathy may be eligible.
Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
9.Has received prior radiotherapy within 4 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=2 weeks of radiotherapy) to non-CNS disease.
10.Has received a live vaccine within 4 weeks or for a period of at least 5 half-lives of the respective drug/IMP (whichever is longer) before Screening and during Screening for this trial. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist®) are live attenuated vaccines and are not allowed.
11.Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks or for a period of at least 5 half-lives of the respective drug/IMP (whichever is longer) before Screening and during Screening for this trial.
Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks or at least 5 half-lives of the respective drug/IMP (whichever is longer) after the last dose of the previous investigational agent.
12.Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
13.Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
14.Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Objective response rate (ORR);Secondary Objective: - time to recurrence (TTR)<br>- recurrence free survival<br>- overall survival (OS)<br>- safety and tolerability<br>- identification of molecular biomarkers predictive for ORR, TTR, recurrence free survival and OS;Primary end point(s): Objective response rate (ORR) ;Timepoint(s) of evaluation of this end point: after two cycles of pembrolizumab and before RFA, MWA, brachytherapy or combination of TACE with RFA, MWA or brachytherapy
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - time to recurrence (TTR)<br>- recurrence free survival<br>- overall survival (OS)<br>- safety and tolerability<br>- identification of molecular biomarkers predictive for ORR, TTR, recurrence free survival and OS;Timepoint(s) of evaluation of this end point: End of study