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Hepatocellular Carcinoma Non-resectablePhase 2DEMANDNCT04224636

Atezolizumab/Bevacizumab Followed by On-demand TACE or Initial Synchronous Treatment With TACE and Atezolizumab/Bevacizumab

A Phase 2 study testing Atezolizumab Injection, Bevacizumab Injection in people with Hepatocellular Carcinoma Non-resectable, run by Ludwig-Maximilians - University of Munich at 7 sites in Germany.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Aim of the study is to evaluate the efficacy of up-front atezolizumab/ bevacizumab (Atezo/Bev) followed by on-demand selective transarterial chemoembolization (sdTACE) and of initial synchronous treatment with TACE and Atezo/Bev in the treatment of unresectable HCC patients. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hepatocellular Carcinoma Non-resectable
What is being tested?
Atezolizumab Injection, Bevacizumab Injection
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
106 participants
Where
7 sitesGermany
Study dates
10 Jun 2020to 1 Mar 2025
Phase
Phase 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

  • Patient's signed informed consent
  • Age ≥18 years at time of signing Informed Consent Form
  • Ability to comply with the study protocol, according to investigator's judgement
  • Life expectancy of at least 12 weeks
  • HCC with histologically confirmed diagnosis
  • Disease that is not amenable to curative surgical and/or local ablation but eligible for TACE
Show all 10Show fewer
  • ECOG Performance Status of 0 or 1
  • Child-Pugh class A or B7
  • Adequate hematologic and end-organ function
  • Negative HIV test at screening

Who cannot join

  • Diffuse HCC or presence of vascular invasion or extrahepatic spread or more than 7 lesions or at least one lesion >= 7 cm
  • Clinically relevant ascites
  • Uncontrolled pleural effusion or pericardial effusion
  • History or presence of hepatic encephalopathy
  • Co-infection of HBV and HCV
  • Patients on a liver transplantation list.
Show all 43Show fewer
  • Prior systemic therapy for HCC
  • Prior treatment with TACE or selective internal radiation treatment (SIRT)
  • Any condition representing a contraindication to TACE
  • Major gastrointestinal bleeding within 4 weeks prior to randomization, untreated or incompletely treated varices with bleeding or high-risk for bleeding.
  • Active or history of autoimmune disease or immune deficiency
  • Prior allogeneic stem cell or solid organ transplantation
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
  • Active tuberculosis
  • Severe infection requiring antibiotics within 4 weeks prior to randomization
  • Significant cardiovascular disease
  • History of congenital long QT syndrome or corrected QT interval >500 ms at screening ECG
  • Inadequately controlled arterial hypertension or prior history of hypertensive crisis or hypertensive encephalopathy
  • Significant vascular disease including aortic aneurysm requiring surgical repair or peripheral arterial thrombosis with 6 months prior to randomization
  • History of abdominal or tracheoesophageal fistula or gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to randomization.
  • History or clinical signs of gastrointestinal obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding. Evidence of abdominal free air that is not explained by paracentesis or recent surgical procedure
  • History of intra-abdominal inflammatory process within 6 months prior to randomization, including but not limited to peptic ulcer disease, diverticulitis, or colitis
  • Evidence of bleeding diathesis or significant coagulopathy
  • Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications.
  • Uncontrolled tumor-related pain. Patients requiring pain medication must be on a stable regimen at enrollment.
  • Severe, non healing or dehisced wound, active ulcer, or untreated bone fracture
  • History of malignancy other than HCC, with the exception of patients who have been disease-free for at least five years before enrollment or patients with adequately treated and completely resected basal cell or squamous cell skin cancer, in situ cervical, breast or prostate cancer, stage I uterine cancer
  • Current or recent (within 10 days of randomization) use of acetylsalicyclic acid or treatment with dipyramidole, ticlopidine, clopidogrel, and cilostazol
  • Current or recent (within 10 days prior to randomization) use of full dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purpose.
  • Chronic daily treatment with a nonsteroidal anti-inflammatory drug (NSAID). Occasional use of NSAIDs for the symptomatic relief of medical conditions such as headache or fever is allowed.
  • Treatment with a live, attenuated vaccine within 4 weeks prior to randomization, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the last dose of atezolizumab
  • Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and antiPD-L1 therapeutic antibodies
  • Hypersensitivity to atezolizumab or bevacizumab or any of the excipients, known hypersensitivity to Chinese hamster ovary cell products, known hypersensitivity to human or humanized antibodies
  • Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to randomization
  • Treatment with systemic immunosuppressive medication within 2 weeks prior to randomization, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions:
  • Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible.
  • Inhaled corticosteroids for chronic obstructive pulmonary disease or bronchial asthma, supplemental mineralocorticosteroids or low-dose corticosteroids for adrenalcortical insufficiency are allowed.
  • Major surgical procedure other than for diagnosis, open biopsy, or significant traumatic injury within 28 days prior to randomization, or abdominal surgery, abdominal interventions or significant abdominal traumatic injury within 60 days prior to randomization or anticipation of need for major surgical procedure during the course of the study or non-recovery from side effects of any such procedure
  • Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 3 days prior to the first dose of bevacizumab
  • Pregnant or breastfeeding females
  • Participation in a clinical trial or experimental drug treatment within 28 days prior to inclusion in the clinical trial or within a period of 5 half-lives of the substances administered in a clinical trial or during an experimental drug treatment prior to inclusion in the clinical trial, depending on which period is longest, or simultaneous participation in another clinical trial while taking part in this clinical trial.
  • Patient committed to an institution by virtue of an order issued either by the judicial or the administrative authorities
  • Patient possibly dependent from the investigator including the spouse, children and close relatives of any investigator

Trial locations and contacts

7 sites in 1 country.

Enrico De Toni, MD contact

+49 89 4400 0

enrico.detoni@med.uni-muenchen.de

7 sites in 1 country

Germany7 sites, 7 recruiting

  • University of Bonn

    Bonn

    Maria Gonzales-Carmona, MD

    Maria.Gonzalez-Carmona@ukbonn.de

    Recruiting

  • University Hospital Cologne

    Cologne, 50931

    Dirk Waldschmidt, MD

    Recruiting

  • Hospital of the University of Munich

    Munich, 81377

    Najib Ben-Khaled, MD, +49 (0)894400-0, najib.benkhaled@med.uni-muenchen.de

    Alexander Philipp, MD

    Recruiting

  • Klinikum Rechts der Isar of the Technical University Munich

    Munich, 81675

    Ursula Ehmer, MD

    Recruiting

  • University Hospital Regensburg

    Regensburg, 93053

    Arne Kandulski, MD

    Recruiting

  • University Hospital Tübingen

    Tübingen, 72076

    Michael Bitzer, MD

    Recruiting

  • Würzburg University Hospital

    Würzburg

    Florian Reiter, MD, Reiter_F@ukw.de

    Recruiting

Other trials in Germany

About this study

Official title: A Randomized, 2-arm Non-comparative Phase II Study on the Efficacy of Atezolizumab and Roche Bevacizumab (Atezo/Bev) Followed by On-demand Selective TACE (sdTACE) Upon Detection of Disease Progression or of Initial Synchronous Treatment With TACE and Atezo/Bev on 24-months Survival Rate in the Treatment of Unresectable Hepatocellular Carcinoma Patients

Aim of the study is to evaluate the efficacy of up-front atezolizumab/ bevacizumab (Atezo/Bev) followed by on-demand selective transarterial chemoembolization (sdTACE) and of initial synchronous treatment with TACE and Atezo/Bev in the treatment of unresectable HCC patients.

Being tested
Atezolizumab Injection, Bevacizumab Injection

What participants receive

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

  • Atezolizumab Injection, Bevacizumab InjectionCombination product

    Also called Chemoembolisation (TACE)

    Atezolizumab and Bevacizumab will be administered prior to or in combination with TACE

Study groups in NCT04224636
Study groupRoleWhat they receive
Up-front Atezo/Bev, then TACEExperimentalPatients will receive atezolizumab and bevacizumab iv every three weeks for up to 24 months. Upon detection of at least one unequivocal progressive hepatic lesion, selective TACE directed against progressive lesion(s) (sdTACE) will be performed. RFA or MWA are permitted as alternative to TACE to treat one or more lesion that cannot be reasonably selectively targeted by TACE
Receives: Combination Product: Atezolizumab Injection, Bevacizumab Injection
Atezo/Bev combined with TACEExperimentalFirst TACE will be performed as selectively as possible against all viable tumor lesions. Atezo/Bev will be initiated within three days from TACE. Upon detection of at least one unequivocal progressive hepatic lesion, treatment with Atezo/Bev will be continued if RFA or MWA can be used to treat this/these progressive lesion.
Receives: Combination Product: Atezolizumab Injection, Bevacizumab Injection

What is being measured

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

  1. Overall response rate (ORR)

    Response is defined by RECIST 1.1 and mRECIST

    Measured: 24 months

Secondary outcomes (12)

  1. Median overall survival (mOS)

    Defined as the time from treatment initiation until death

    Measured: 24 months

  2. Progression-free survival (PFS)

    Progression is defined according RECIST 1.1 and mRECIST

    Measured: 24 months

  3. 24-months survival rate

    Percentage of patients alive after 24 months since randomization

    Measured: 24 months

  4. Complete response rate (CRR)

    Defined by the percentage of patients with disappearance of tumor manifestation at radiological evaluation

    Measured: 24 months

  5. Disease control rate (DCR)

    Defined as the percentage of patients who have achieved complete response, partial response and stable disease

    Measured: 24 months

  6. Time to deterioration of liver function

    Defined as time from randomization to worsening of CTCAE grade for any of these parameters: aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, albumin, and international normalized ratio (INR)

    Measured: 24 months

  7. Time to untreatable progression

    defined as time from randomization to progression not amenable to local treatment as per protocol, occurrence of vascular invasion or of extrahepatic spread, worsening of liver function to Child-Pugh score 8 or higher

    Measured: 24 months

  8. Time to stage-progression

    Defined as time from randomization to disease progression to BCLC C stage

    Measured: 24 months

  9. Time to first TACE (arm A)

    Defined as time from randomization to disease to the first TACE

    Measured: 24 months

  10. Quality of life (QOL)

    Standardized assessment will be performed by using EORTC QLQ-C30 - European Organisation for Research and Treatment of Cancer - Quality of Life Core Questionnaire 30 items

    Measured: 24 months

  11. Quality of life (QOL)

    Standardized assessment will be performed by using EORTC QLQ-HCC18 - European Organisation for Research and Treatment of Cancer - Quality of Life Core Questionnaire - Hepatocellular carcinoma module 18

    Measured: 24 months

  12. Adverse Events

    Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0

    Measured: 24 months

Timeline

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

  1. First posted13 Jan 2020
  2. Study start10 Jun 2020
  3. Primary completion1 Mar 2025 (estimated)
  4. Study completion1 Mar 2025 (estimated)

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
106 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04224636
Sponsor's protocol ID
AIO-HEP-0418
Other IDs
2019-002430-36, 2019
Acronym
DEMAND
Status last verified
Jun 2024
First submitted
19 Dec 2019
Last updated
14 Jun 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • De Toni EN. Immune checkpoint inhibitors: use them early, combined and instead of TACE? Gut. 2020 Oct;69(10):1887-1888. doi: 10.1136/gutjnl-2019-319658. Epub 2019 Oct 14. No abstract available.

    PubMed 31611301

  • Ben Khaled N, Seidensticker M, Ricke J, Mayerle J, Oehrle B, Rossler D, Teupser D, Ehmer U, Bitzer M, Waldschmidt D, Fuchs M, Reuken PA, Lange CM, Wege H, Kandulski A, Dechene A, Venerito M, Berres ML, Luedde T, Kubisch I, Reiter FP, De Toni EN. Atezolizumab and bevacizumab with transarterial chemoembolization in hepatocellular carcinoma: the DEMAND trial protocol. Future Oncol. 2022 Apr;18(12):1423-1435. doi: 10.2217/fon-2021-1261. Epub 2022 Jan 27.

    PubMed 35081747

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Atezolizumab Injection, Bevacizumab Injection in people with Hepatocellular Carcinoma Non-resectable, run by Ludwig-Maximilians - University of Munich at 7 sites in Germany.

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 10 inclusion and 43 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: status not confirmed, as of the sponsor's last update on 14 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Germany. 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 phase mean?

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?

Results are not available in the source record.

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

Contact Enrico De Toni, MD (+49 89 4400 0, enrico.detoni@med.uni-muenchen.de), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall response rate (ORR) (time frame: 24 months). 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 NCT04224636, which also lists 2 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 14 Jun 2024.

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