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Hepatocellular Carcinoma (HCC)MANIFEST-HCCNCT06903663

Pathological and Clinical Features of Patients Treated With ATZ+BEV in Romania

An observational study of Hepatocellular Carcinoma (HCC), run by Adrian Radu Vidra at 4 sites in Romania.

Completed

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

Official record
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Trial summary

Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer and the third most frequent cause of cancer-related death globally. The treatment combination atezolizumab and bevacizumab has been approved as a front-line treatment for unresected or advanced HCC, following the results of the IMBrave 150 clinical… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hepatocellular Carcinoma (HCC)
What is being tested?
Retrospective analysis of assigned treatment
How many people
178 participants
Where
4 sitesRomania
Study dates
22 Oct 2025to 29 May 2026
Phase
Observational
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

Study population: Patientd with a radiologically- confirmed diagnosis of advanced or unresectable HCC undergoing combination therapy with atezolizumab and bevacizumab as first-line.

Who may be able to join

  • Adult women and men (≥ 18 years of age) with proven initial diagnosis of HCC with evidence of loco-regional recurrent or advanced disease not amenable to resection.
  • At least one cycle of therapy with ATZ plus BEV.
  • Eligible individuals will be required to have Baseline (pre-index) EGD available
  • No prior systemic therapy for HCC.
  • Evaluable disease as defined per modified Response Evaluation Criteria in Solid Tumours (mRECIST) V1.1 criterion (At least 1 evaluable CT result over the entire available index and post-index period, excluding the baseline).
  • Patients identified from the patient registry in the hospital with treatment charts between April 1, 2022- December 31, 2024 (index date).
  • Eligible individuals will be required to have data available prior to the index date (pre-index period; baseline characteristics).

Who cannot join

  • A diagnosis of any other primary cancer prior to the index date
  • ATZ plus BEV treatment as part of a clinical trial
  • ATZ or BEV given off-label
  • Patients with incomplete medical records
  • Patients receiving other investigational drugs
  • History of hepatic encephalopathy
  • Patients with brain metastasis
  • HBV and HBC co-infection

Trial locations and contacts

4 sites in 1 country.

Romania4 sites

  • Fundeni Clinical Institute

    Bucharest, Bucharest, 022328

  • Regional Institute of Gastroenterology and Hepatology "Prof. Dr. Octavian Fodor"

    Cluj-Napoca, Cluj, 400162

  • Regional Institute of Oncology

    Iași, Iaşi, 700483

  • Oncohelp

    Timișoara, Timiș County, 300239

Other trials in Romania

About this study

Official title: A Multi-Centric, Retrospective, Real-World Study on First-Line Therapy With Atezolizumab Plus Bevacizumab for Advanced or Unresectable Hepatocellular Carcinoma in Romanian Population

Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer and the third most frequent cause of cancer-related death globally. The treatment combination atezolizumab and bevacizumab has been approved as a front-line treatment for unresected or advanced HCC, following the results of the IMBrave 150 clinical study.

Hepatocellular carcinoma represent a significant public health burden in Romania due to strong association with chronic liver diseases, associated with Hepatitis B and C infections, alcohol-related liver disease., and metabolic dysfunction-associated staetohepatitis. The key challenge in this context remains identifying those patients who may benefit the most from the combination treatment.

Read more

This retrospective, multicentric study is coordinated by Dr. Adrian Radu Vidra (Lead Investigator and Sponsor) from Regional Institute of Gastroenterology and Hepatology "Prof. Dr. Octavian Fodor" Cluj-Napoca (Coordinating Site) to identify pathological and clinical features of HCC that can influence patients' response to treatment.

This retrospective analysis will collect data from four (4) different centers located in Romania (Cluj-Napoca, Iasi, Timisoara and Bucharest).

Read the detailed description

Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer and the third most frequent cause of cancer-related death globally.

Patients with cirrhosis are at highest risk of developing this malignant disease, and the association between liver cirrhosis and HCC is accountable for a high rate of treatment failure. Survival data reported from Europe and United States show that HCC is associated with a very poor prognosis, with the 5-year survival around 5% in most countries.

The geographic variability in the incidence of primary liver cancer is largely explained by the distribution and the natural history of the hepatitis B and C viruses. Etiologic factors for HCC tend to differentiate in developing countries.

With the incidence of obesity, type II diabetes mellitus (T2DM) and metabolic syndrome continuing to increase in Europe, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), which can lead to fibrosis and cirrhosis, may become the most common cause of HCC in developed countries in the near future.

The present study is a retrospective cohort study. The study will collect data on adult Caucasion population, with proven initial diagnosis of HCC with evidence of loco-regional recurrent or advanced disease not amenable to resection, with at least one cycle of therapy with ATZ plus BEV and no prior systemic therapy for HCC, identified in the patient registry with tretament charts between 1 April 2022- 31 December 2024 (index date).

The data cut-off date is 31 December 2025.

The primary study endpoint is Demographic and Clinical characteristics analyzed by descriptive statistics.

Secondary endpoints include OS, PFS, DoR, DCR, ORR and safety. Subgroup analyses based on baseline characteristics (e.g., prior therapies, ECOG performance) will be performed.

Data on baseline characteristics, radiological response, treatment patterns and adverse events will be summarized using descriptive statistics.

Continuous variables will be presented as median and full range, and categorical variables will be reported as frequencies and percentages.

Median duration of therapy was defined as the time from the first administration until the last administration of the combination ATZ plus BEV.

Treatment exposure will be calculated as follows:

Number of days exposed = date of last dose minus date of first dose plus 1 day minus periods of interruptions.

Patients with at least one staging imaging assessment (excluding the baseline confirmatory CT result) will be evaluated for radiological response.

Vital status for all patients will be recorded. Where possible, death and reason for death (disease progression or death from any cause) will be captured.

PFS is defined as the time from the date of the first therapy administration of ATZ plus BEV until radiological disease progression or death, whatever occurred first. Patients still alive and without radiologically confirmed progression at the date of the last contact or data cut-off will be censored.

OS will be defined as the time from the start of the treatment with atezolizumab and bevacizumab until the date of death.

Survival curves will be calculated with the Kaplan-Meier method and compared by means of the log-rank test.

Being tested
Retrospective analysis of assigned treatment
Keywords
Pathological features of HCC, real-world study, Romania, IRGH, Radu Vidra, etiology of liver disease
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

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

  • Retrospective analysis of assigned treatmentOther

    Retrospective analysis of assigned treatment

Study groups in NCT06903663
Study groupRoleWhat they receive
Adult women and men (≥ 18 years of age) with proven initial diagnosis of HCCPatients with HCC following treatment with ATZ plus BEV identified from the patient registry in the hospital with treatment charts between April 1, 2022- December 31, 2024 (index date).
Receives: Other: Retrospective analysis of assigned treatment

What is being measured

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

  1. Description of pathological and clinical features of HCC

    The defined primary study outcome is to describe pathological and clinical features of HCC that can influence patients' response to treatment in a real-life setting.

    Measured: Treatments performed between 01 April 2022- 31 December 2024; Data cut-off date 31 December 2025.

Secondary outcomes (6)

  1. Progression-Free Survival (PFS) according to viral and non-viral etiology in the selected cohort

    PFS is defined as the time from tretament initiation to documented/ radiological disease progression or death, whatever occurred first.

    Measured: 12 months

  2. Overall Survival (OS) for patients treated with the combination therapy

    OS will be defined as the elapsed time from onset of the treatment to death from any cause.

    Measured: 12 months

  3. Disease Control Rate (DCR)

    DCR will be calculated per modified Response Evaluation Criteria in Solid Tumors (mRECIST) V1.1 criterion, as the proportion of patients with best overall response to protocol therapy of complete response (CR), partial response (PR) or stable disease (SD) that is maintained for at least 12 weeks.

    Measured: 12 months

  4. Objective Response Rate (ORR)

    ORR will be defined as the proportion of the patients with a confirmed CR or PR, as per mRECIST V1.1 criterion.

    Measured: 12 months

  5. Duration of Response (DOR)

    DOR will be defined as the elapsed time from documented tumor response to documented disease progression or death from any cause.

    Measured: 12 months

  6. Overall safety of the combination therapy ATZ +BEV

    Safety assessment will consist of monitoring the incidence of all adverse events observed following the treatment with ATZ plus BEV, graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5. Safety events will be stratified by type of events, grades, seriousness and will be collected at time points defined in the study flowchart.

    Measured: 12 months

Timeline

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

  1. First posted1 Apr 2025
  2. Study start22 Oct 2025
  3. Primary completion29 May 2026
  4. Study completion29 May 2026

Resources

More details

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

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Retrospective
Enrolment
178 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06903663
Sponsor's protocol ID
MANIFEST-HCC-RO
Acronym
MANIFEST-HCC
Status last verified
Nov 2026
First submitted
12 Feb 2025
Last updated
6 Nov 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Kulkarni AV, Tevethia H, Kumar K, Premkumar M, Muttaiah MD, Hiraoka A, Hatanaka T, Tada T, Kumada T, Kakizaki S, Vogel A, Finn RS, Rao PN, Pillai A, Reddy DN, Singal AG. Effectiveness and safety of atezolizumab-bevacizumab in patients with unresectable hepatocellular carcinoma: a systematic review and meta-analysis. EClinicalMedicine. 2023 Aug 30;63:102179. doi: 10.1016/j.eclinm.2023.102179. eCollection 2023 Sep.

    PubMed 37680945

  • Storandt MH, Zemla TJ, Patell K, Naleid N, Gile JJ, Tran NH, Chakrabarti S, Jin Z, Borad M, Mahipal A. Atezolizumab plus bevacizumab as first-line systemic therapy for hepatocellular carcinoma: a multi-institutional cohort study. Oncologist. 2024 Nov 4;29(11):986-996. doi: 10.1093/oncolo/oyae142.

    PubMed 38979643

  • Bialecki ES, Di Bisceglie AM. Diagnosis of hepatocellular carcinoma. HPB (Oxford). 2005;7(1):26-34. doi: 10.1080/13651820410024049.

    PubMed 18333158

  • Pinero F, da Fonseca LG. Trial eligibility in advanced hepatocellular carcinoma: Does it support clinical practice in underrepresented subgroups? World J Gastroenterol. 2021 Jun 28;27(24):3429-3439. doi: 10.3748/wjg.v27.i24.3429.

    PubMed 34239261

  • Singal AG, Ozgurdal K, Fan X, Vassilev Z, Pan X, Multani JK, Chen CC, Zhou Z, He J, Pisa F. Real-World Systemic Treatment Patterns after Atezolizumab and Bevacizumab in Patients with Hepatocellular Carcinoma in the United States. Cancers (Basel). 2023 Nov 22;15(23):5532. doi: 10.3390/cancers15235532.

    PubMed 38067235

  • Cheng AL, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Lim HY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Ma N, Nicholas A, Wang Y, Li L, Zhu AX, Finn RS. Updated efficacy and safety data from IMbrave150: Atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma. J Hepatol. 2022 Apr;76(4):862-873. doi: 10.1016/j.jhep.2021.11.030. Epub 2021 Dec 11.

    PubMed 34902530

  • Qin S, Chen M, Cheng AL, Kaseb AO, Kudo M, Lee HC, Yopp AC, Zhou J, Wang L, Wen X, Heo J, Tak WY, Nakamura S, Numata K, Uguen T, Hsiehchen D, Cha E, Hack SP, Lian Q, Ma N, Spahn JH, Wang Y, Wu C, Chow PKH; IMbrave050 investigators. Atezolizumab plus bevacizumab versus active surveillance in patients with resected or ablated high-risk hepatocellular carcinoma (IMbrave050): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2023 Nov 18;402(10415):1835-1847. doi: 10.1016/S0140-6736(23)01796-8. Epub 2023 Oct 20.

    PubMed 37871608

  • Vogel A, Meyer T, Saborowski A. IMbrave050: the first step towards adjuvant therapy in hepatocellular carcinoma. Lancet. 2023 Nov 18;402(10415):1806-1807. doi: 10.1016/S0140-6736(23)01962-1. Epub 2023 Oct 23. No abstract available.

    PubMed 37883983

  • Meyers BM, Knox JJ, Liu DM, McLeod D, Ramjeesingh R, Tam VC, Lim HJ. The evolution of immune checkpoint inhibitor combinations in advanced hepatocellular carcinoma - A systematic review. Cancer Treat Rev. 2023 Jul;118:102584. doi: 10.1016/j.ctrv.2023.102584. Epub 2023 May 27.

    PubMed 37336142

  • Leowattana W, Leowattana T, Leowattana P. Systemic treatment for unresectable hepatocellular carcinoma. World J Gastroenterol. 2023 Mar 14;29(10):1551-1568. doi: 10.3748/wjg.v29.i10.1551.

    PubMed 36970588

  • Cholankeril G, Patel R, Khurana S, Satapathy SK. Hepatocellular carcinoma in non-alcoholic steatohepatitis: Current knowledge and implications for management. World J Hepatol. 2017 Apr 18;9(11):533-543. doi: 10.4254/wjh.v9.i11.533.

    PubMed 28469809

  • Bosch FX, Ribes J, Diaz M, Cleries R. Primary liver cancer: worldwide incidence and trends. Gastroenterology. 2004 Nov;127(5 Suppl 1):S5-S16. doi: 10.1053/j.gastro.2004.09.011.

    PubMed 15508102

  • Capocaccia R, Sant M, Berrino F, Simonetti A, Santi V, Trevisani F; EUROCARE Working Group. Hepatocellular carcinoma: trends of incidence and survival in Europe and the United States at the end of the 20th century. Am J Gastroenterol. 2007 Aug;102(8):1661-70; quiz 1660, 1671. doi: 10.1111/j.1572-0241.2007.01337.x. Epub 2007 Jun 6.

    PubMed 17555459

  • European Association for the Study of the Liver. EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma. J Hepatol. 2025 Feb;82(2):315-374. doi: 10.1016/j.jhep.2024.08.028. Epub 2024 Dec 17.

    PubMed 39690085

  • Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet. 2012 Mar 31;379(9822):1245-55. doi: 10.1016/S0140-6736(11)61347-0. Epub 2012 Feb 20.

    PubMed 22353262

Questions about this trial

What is this clinical trial studying?

An observational study of Hepatocellular Carcinoma (HCC), run by Adrian Radu Vidra at 4 sites in Romania.

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 7 inclusion and 8 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 6 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Romania. 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.

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?

Description of pathological and clinical features of HCC (time frame: Treatments performed between 01 April 2022- 31 December 2024; Data cut-off date 31 December 2025.). 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 NCT06903663, which also lists 15 linked publications.

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 6 Nov 2026.

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