IMA970A Plus CV8102 in Very Early, Early and Intermediate Stage Hepatocellular Carcinoma Patients
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|ClinicalTrials.gov Identifier: NCT03203005|
Recruitment Status : Recruiting
First Posted : June 29, 2017
Last Update Posted : December 21, 2018
|Condition or disease||Intervention/treatment||Phase|
|Hepatocellular Carcinoma||Drug: IMA970A plus CV8102 and Cyclophosphamide||Phase 1 Phase 2|
The trial is designed as a single-arm, open-label, multi-center, first-in-man phase I/II study investigating an off-the-shelf, multi-peptide-based HCC vaccine (IMA970A) plus CV8102 adjuvant (RNAdjuvant®) following a single pre-vaccination infusion of low-dose cyclophosphamide (CY) acting as an immunomodulator, in patients with very early, early and intermediate stage HCC.
The study treatment is applied without any concomitant anti-tumor therapy, with the intention to reduce the risk of tumor recurrence/progression in patients who have received all indicated standard treatments.
Overall, it is planned to treat about 40 patients with IMA970A (off-the-shelf vaccine) plus CV8102 (adjuvant) plus a single low-dose of pre-vaccination CY acting as an immunomodulator in the HepaVac-101 study.
Patients are requested to sign the 1st informed consent (IC 1) for screening 1 procedures (blood drawings for Human Leukocyte Antigen (HLA) typing and for cellular immunomonitoring, capture of demographics and staging of disease [routinely performed, older images may be used if requirements are met]), which takes up to 4 weeks. Thereafter, patients receive indicated standard treatment followed by recovery, which lasts for at least 4 weeks and up to 12 weeks. The main-phase with full safety surveillance starts with the patient's signature of the 2nd informed consent (IC 2) and lasts until the end of the EoV (End-of-Visit, Visit 10) Visit (4-6 weeks after last vaccination). For each patient this main-phase lasts up to approx. 6.5 months consisting of up to 4 weeks screening 2, about 4.5 months vaccination period and about 4 weeks follow up (until EOV Visit [Visit 10]).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Trial of IMA970A Plus CV8102 Following a Single Pre-vaccination Infusion of Cyclophosphamide in Patients With Very Early, Early and Intermediate Stage of Hepatocellular Carcinoma After Any Standard Treatments|
|Actual Study Start Date :||September 18, 2017|
|Estimated Primary Completion Date :||January 30, 2020|
|Estimated Study Completion Date :||January 30, 2020|
Experimental: IMA970A plus CV8102 and Cyclophosphamide
Investigational treatment with IMA970A, CV8102, Cyclophosphamide
Drug: IMA970A plus CV8102 and Cyclophosphamide
Study treatment starts with a single intravenous infusion of 300mg/m2 Cyclophosphamide.
Three days later patients start vaccination therapy with IMA970A plus CV8102 Each vaccination consists of a dose of 6.80 milligrams (mg) IMA970A (containing approx. 400 micrograms [µg] of each individual peptide) followed by a dose of 50 µg CV8102. First IMA970A is injected intradermally (i.d.) and about 10 minutes later CV8102 is injected i.d. at the same vaccination site in close proximity. Patients will receive 4 vaccinations at weekly intervals followed by 5 vaccinations at 3-weekly intervals for a total duration of about 4.5 months.
Other Name: Cyclophosphamide Injection 1 g
- Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [ Time Frame: Through study completion, up to two years ]Safety assessments will consist of continuous monitoring and reporting of adverse events (AEs) including serious adverse events (SAEs), regular monitoring of vital signs, ECOG performance status and regular conduct of physical examinations and laboratory assessments (hematology, clinical [bio]chemistry including C reactive protein (CRP) and Glomerular Filtration rate (GFR), coagulation test, assessment of viral infection, thyroid function test (TFT), urinalysis), electrocardiogram (ECG) and pregnancy tests (if applicable). Additionally, an Independent Data Safety Monitoring Board (DSMB) will be implemented to evaluate safety data independently and at defined intervals.
- Immunogenicity (T-cell response in peripheral blood) [ Time Frame: Up to two years ]The assessment of immunogenicity will be performed for all patients using standardized immunomonitoring assays. Peripheral blood mononuclear cells (PBMCs) of patients will be analyzed for the occurrence of T-cell responses to peptides contained in IMA970A vaccine before application of standard therapy, such as before and after vaccination. The induction of immune responses by IMA970A vaccine will be subsequently analyzed.
- Additional immunological parameters in blood (e.g. regulatory T-cells, myeloid-derived suppressor cells) [ Time Frame: Up to two years ]Analysis of other immune cell populations that may influence T-cell responses such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSC) (cellular biomarkers) will be performed using PBMCs
- Infiltrating T-lymphocytes, immune cells and potential other (bio)markers in tumor tissue [ Time Frame: Up to two years ]Analysis of paraffin-embedded tumor tissues (also potentially in liquid-nitrogen frozen tissue, if available) will be performed to characterize both the tumor cells and the tumor-infiltrating components by immunohistochemistry (IHC) and potentially other analysis techniques. Classical hematoxylin-eosin (HE) staining will be first performed to assess the cellular and stroma composition of the tumor tissue. Markers such as Cytokeratin 8, Cytokeratin 18 and HepPar-1, will be assessed to distinguish tumor cells from other cellular components. The tumor infiltrating cells will be characterized to assess leukocyte subpopulations such as myeloid (monocyte-macrophages, granulocytes) and lymphoid (T, B, NK) cells.
- Assessment of the potential impact of the standard therapy on the natural imune response to peptides contained in IMA970A [ Time Frame: Up to two years ]The assessment of the natural immune response to peptides contained in IMA970A will be performed before start of standard anti-tumor therapy and thereafter to assess whether the selected standard therapy has an influence on a potentially pre-existing (natural) immune response.
- Time to progression (TTP) [ Time Frame: Up to two years ]The time-related secondary efficacy endpoint for the trial is time-to-progression, with time being measured from baseline CT/MRI scan (at Visit B) to documented tumor progression.
- Overall survival (OS) [ Time Frame: Patients will be followed for overall survival every 2 months for up to 3 years, after having completed the interventional part of the study at EOV/Visit 10. ]Patients will be followed for overall survival
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): NCT03203005
|Contact: Luigi Buonaguro, MD||+39 081 590 ext firstname.lastname@example.org|
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