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Hepatocellular CarcinomaPhase 1/2NCT03203005

IMA970A Plus CV8102 in Very Early, Early and Intermediate Stage Hepatocellular Carcinoma Patients

A Phase 1/2 study testing IMA970A plus CV8102 and Cyclophosphamide in people with Hepatocellular Carcinoma, run by National Cancer Institute, Naples at 6 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study is being carried out in order to evaluate a new cancer vaccine called IMA970A combined with CV8102, a new adjuvant for the treatment of liver cancer (hepatocellular carcinoma). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hepatocellular Carcinoma
What is being tested?
IMA970A plus CV8102 and Cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
6 sitesin 5 countries
Study dates
18 Sep 2017to 20 Dec 2019
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Aged at least 18 years
  • HLA type: HLA-A*02 and/or HLA-A*24 positive (Screening 1)
  • Very early, early and intermediate stage (Barcelona Clinic Liver Cancer (BCLC) stage 0, A, B disease) hepatocellular carcinoma (HCC) diagnosed by biopsy or resected tissue (pathohistological diagnosis) or imaging findings (non-invasive criteria) following any standard treatment (e.g. hepatic resection, Radiofrequency Ablation / Percutaneous Ethanol injection (RFA/PEI), Transarterial chemoembolization (TACE) and SIRT) and without any evidence of active disease that warrant further treatment
  • Pathohistological diagnosis of HCC based on biopsy is required for all nodules occurring in non-cirrhotic livers, and for those cases with inconclusive or atypical imaging appearance in cirrhotic livers
  • Non-invasive criteria can only be applied to cirrhotic patients and need to be based on imaging techniques obtained by 4-phase multi-detector CT scan or dynamic contrast-enhanced MRI and on the identification of the typical hallmark of HCC (hypervascular in the arterial phase with washout in the portal venous or delayed phase). One imaging technique is sufficient for nodules beyond 1 cm (> 1 cm) in diameter.
  • Patients for whom no standard anti-tumor therapy is indicated for the next 3 months (until after visit 7); thereafter any standard anti-tumor therapies applied for the treatment of BCLC stage 0, A and B HCC (e.g. RFA/PEI, TACE, and SIRT) are allowed to be applied in combination with the study treatment. Patients for whom treatment for advanced disease (e.g. sorafenib) is indicated will be withdrawn from study treatment.
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  • Eastern Cooperative Oncology Group (ECOG) performance status 0
  • Child-Pugh A5-6 and B7 disease or no liver function impairment
  • Able to understand the nature of the study and give written informed consent
  • Willingness and ability to comply with the study protocol for the duration of the study
  • Female patients who are post-menopausal (no menstrual period for a minimum of 1 year without any alternative medical cause), or surgically sterile (bilateral salpingectomy, bilateral oophorectomy, or hysterectomy) or practice a highly effective method of birth control from signing of IC 2 by the patient to visit 10/EoV or last study visit
  • Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation applied intravaginal or transdermal for a minimum of 1 full cycle (based on the patient's usual menstrual cycle period) before first study drug application
  • Progestogen-only hormonal contraception associated with inhibition of ovulation applied via injection or implant for a minimum of 1 full cycle (based on the patient's usual menstrual cycle period) before first study drug application
  • Total abstinence from sexual intercourse is acceptable, if it was established prior to the trial and if this is the preferred and usual lifestyle of the patient.
  • Intrauterine device (IUD) and intrauterine hormone-releasing system (IUS).
  • Male patients willing to use contraception (condoms with spermicidal jellies or cream) or have undergone bilateral orchiectomy and his non-pregnant WOCBP (women of childbearing potential partner) willing to use contraception (a highly effective method of birth control, see criteria above) from signing of IC 2 by the patient to visit 10/EOV or last study visit, however, at least 100 days after application of CY at Visit C

Who cannot join

  • Any prior systemic anti-tumor treatment (including drug or treatment regimen, approved or experimental) within 2 weeks before CY application
  • Concurrent participation in a clinical trial
  • Liver transplanted patients; patients who are on the liver transplantation waiting list are allowed to be enrolled
  • History of other malignancies within the last 3 years except for adequately treated except cervical carcinoma in situ, basal cell carcinoma and superficial bladder tumors [Ta, Tis \& T1] or any cancer curatively treated > 3 years prior to signing of IC 2 by the patient
  • Patients with a history or evidence of systemic autoimmune disease, e.g. rheumatoid arthritis, multiple sclerosis, systemic lupus erythematodes (SLE), scleroderma, Sjögren's syndrome, Wegener's granulomatosis, Guillain-Barre syndrome
  • Need for concomitant treatment with immunosuppressive drugs or other immune-modifying drugs. The use of inhaled and nasally applied steroids, as well as topical steroids outside the vaccination area are permitted
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  • Any medically diagnosed or suspected condition of immunodeficiency or medical history thereof
  • Known HIV infection
  • Any other known infection with a biological agent that can cause a severe disease and poses a severe danger to lab personnel working on patients' blood or tissue. Examples are: rabies, Mycobacterium leprae, Plasmodium falciparum, Coccidiodes immitis
  • Acute and active infections requiring oral or intravenous antibiotics, antiviral or antifungal therapy within 30 days prior to signing of the IC 2 by the patient (exception: Hepatitis B Virus (HBV) and/or Hepatitis C Virus (HCV) infections; direct-acting antivirals may be applied as medically indicated.)
  • Patients undergoing renal dialysis or with relevant chronic renal failure
  • Abnormal laboratory values as specified below:
  • Hematology: Hemoglobin (< 8.5 g/dl), platelets (< 75,000/µl), leukocytes (< 2,500/µl), neutrophils (< 1,000/µl), lymphocytes (< 500/µl)
  • Liver function: serum bilirubin (≥ 3 x ULN), Alanine aminotransferase (ALAT) or Aspartate aminotransferase (ASAT) (≥ 5 x ULN)
  • Renal function: serum creatinine (≥ 1.5 x ULN)
  • Patients with seizure disorder requiring medication (such as steroids or anti-epileptics drugs)
  • Encephalopathy
  • Clinically relevant ascites with the only exception of patients that remain free from symptomatic ascites under low-dose diuretics (Spironolactone >100 mg daily and Furosemide >40 mg daily).
  • Hypersensitivity to the study drugs (CY, IMA970A, or CV8102) including excipients and to CT/MRI contrast agent
  • Known type I allergy to beta-lactam antibiotics
  • Evidence of current alcohol or drug abuse
  • Patient dependent on the sponsor or an investigator (e.g. employee, relative)
  • Serious intercurrent illness, which according to the investigator, poses an undue risk to the patient when participating in the trial, including, but not limited to, any of the following:
  • Clinically significant cardiovascular disease (e.g., uncontrolled hypertension; clinically significant cardiac arrhythmia, clinically significant QT-prolongation),
  • New York Heart Association class III-IV congestive heart failure,
  • Symptomatic peripheral vascular disease,
  • Severe pulmonary dysfunction,
  • Psychiatric illness or known social situation that would preclude study compliance.
  • Systemic inflammatory condition
  • Less than 6 months since any of the following:
  • Myocardial infarction,
  • Severe or unstable angina pectoris,
  • Coronary or peripheral artery bypass graft,
  • Cerebrovascular event incl. transient ischemic attack,
  • Pulmonary embolism / deep vein thrombosis (DVT)
  • Patients with contra-indications for treatment with cyclophosphamide (acute infections, bone-marrow aplasia, urinary tract infection, acute urothelial toxicity from cytotoxic chemotherapy or radiation therapy, urinary outflow obstruction)
  • Pregnancy or breastfeeding
  • Any condition which in the judgment of the investigator would place the patient at undue risk or interfere with the results of the study

Trial locations and contacts

6 sites in 5 countries.

6 sites in 5 countries

Italy2 sites

  • Istituto Nazionale Tumori "Pascale" (INTNA)

    Naples, 80131

  • Ospedale Sacro Cuore-Don Calabria U.O.C. Oncologica Medica

    Negrar, 37024

Other trials in Italy

Belgium1 site

  • Universitair Ziekenhuis Antwerpen (UZA), Division of Gastroenterology and Hepatology

    Edegem, 2650

Other trials in Belgium

Germany1 site

  • Universitätsklinik für Allgemeine, Viszeral- und Transplantationschirurgie

    Tübingen, 72076

Other trials in Germany

Spain1 site

  • Universidad de Navarra (NAVAR), Internal Medicine

    Pamplona, 31008

Other trials in Spain

United Kingdom1 site

  • The University of Birmingham, School of Immunity and Infection, College of Medical and Dental Science (BHAM)

    Birmingham, B152TT

Other trials in United Kingdom

About this study

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

This study is being carried out in order to evaluate a new cancer vaccine called IMA970A combined with CV8102, a new adjuvant for the treatment of liver cancer (hepatocellular carcinoma). It will be investigated whether IMA970A and CV8102 is safe and can trigger an immune response against the tumor, which may prevent the tumor (cancer) from recurring or spreading or may even lead to tumor shrinkage following the standard treatments the patients have previously received.

Read the detailed description

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]).

Being tested
IMA970A plus CV8102 and Cyclophosphamide
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IMA970A plus CV8102 and CyclophosphamideDrug

    Also called Cyclophosphamide Injection 1 g

    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.

Study groups in NCT03203005
Study groupRoleWhat they receive
IMA970A plus CV8102 and CyclophosphamideExperimentalInvestigational treatment with IMA970A, CV8102, Cyclophosphamide
Receives: Drug: IMA970A plus CV8102 and Cyclophosphamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)

    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.

    Measured: Through study completion, up to two years

  2. Immunogenicity (T-cell response in peripheral blood)

    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.

    Measured: Up to two years

Secondary outcomes (5)

  1. Additional immunological parameters in blood (e.g. regulatory T-cells, myeloid-derived suppressor cells)

    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

    Measured: Up to two years

  2. Infiltrating T-lymphocytes, immune cells and potential other (bio)markers in tumor tissue

    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.

    Measured: Up to two years

  3. Assessment of the potential impact of the standard therapy on the natural imune response to peptides contained in IMA970A

    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.

    Measured: Up to two years

  4. Time to progression (TTP)

    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.

    Measured: Up to two years

  5. Overall survival (OS)

    Patients will be followed for overall survival

    Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jun 2017
  2. Study start18 Sep 2017
  3. Primary completion20 Dec 2019
  4. Study completion20 Dec 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03203005
Sponsor's protocol ID
HepaVac-101
Status last verified
Jan 2020
First submitted
13 Jun 2017
Last updated
5 Feb 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Loffler MW, Gori S, Izzo F, Mayer-Mokler A, Ascierto PA, Konigsrainer A, Ma YT, Sangro B, Francque S, Vonghia L, Inno A, Avallone A, Ludwig J, Alcoba DD, Flohr C, Aslan K, Mendrzyk R, Schuster H, Borrelli M, Valmori D, Chaumette T, Heidenreich R, Gouttefangeas C, Forlani G, Tagliamonte M, Fusco C, Penta R, Inarrairaegui M, Gnad-Vogt U, Reinhardt C, Weinschenk T, Accolla RS, Singh-Jasuja H, Rammensee HG, Buonaguro L. Phase I/II Multicenter Trial of a Novel Therapeutic Cancer Vaccine, HepaVac-101, for Hepatocellular Carcinoma. Clin Cancer Res. 2022 Jun 13;28(12):2555-2566. doi: 10.1158/1078-0432.CCR-21-4424.

    PubMed 35421231

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing IMA970A plus CV8102 and Cyclophosphamide in people with Hepatocellular Carcinoma, run by National Cancer Institute, Naples at 6 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Italy, Belgium, Germany, Spain, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) (time frame: Through study completion, up to two years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03203005, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2020.

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