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JOURNAL ONKOLOGIE – STUDIE

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

Rekrutierend

NCT-Nummer:
NCT04224636

Studienbeginn:
April 2020

Letztes Update:
26.10.2020

Wirkstoff:
-

Indikation (Clinical Trials):
Carcinoma, Carcinoma, Hepatocellular

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Ludwig-Maximilians - University of Munich

Collaborator:
-

Kontakt

Studienlocations (3 von 7)

Hospital of the University of Munich
81377 Munich
(Bayern)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Enrico N De Toni, MD
Phone: +49 (0)894400-0
E-Mail: enrico.detoni@med.uni-muenchen.de
» Ansprechpartner anzeigen
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Studien-Informationen

Brief 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.

Ein-/Ausschlusskriterien

Key Inclusion Criteria

1. Patient's signed informed consent

2. Age ≥18 years at time of signing Informed Consent Form

3. Ability to comply with the study protocol, according to investigator's judgement

4. Life expectancy of at least 12 weeks

5. HCC with histologically confirmed diagnosis

6. Disease that is not amenable to curative surgical and/or local ablation but eligible

for TACE

7. ECOG Performance Status of 0 or 1

8. Child-Pugh class A or B7

9. Adequate hematologic and end-organ function

10. Negative HIV test at screening

Key Exclusion Criteria

1. Diffuse HCC or presence of vascular invasion or extrahepatic spread or more than 7

lesions or at least one lesion >= 7 cm

2. Clinically relevant ascites

3. Uncontrolled pleural effusion or pericardial effusion

4. History or presence of hepatic encephalopathy

5. Co-infection of HBV and HCV

6. Patients on a liver transplantation list.

7. Prior systemic therapy for HCC

8. Prior treatment with TACE or selective internal radiation treatment (SIRT)

9. Any condition representing a contraindication to TACE

10. Major gastrointestinal bleeding within 4 weeks prior to randomization, untreated or

incompletely treated varices with bleeding or high-risk for bleeding.

11. Active or history of autoimmune disease or immune deficiency

12. Prior allogeneic stem cell or solid organ transplantation

13. 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

14. Active tuberculosis

15. Severe infection requiring antibiotics within 4 weeks prior to randomization

16. Significant cardiovascular disease

17. History of congenital long QT syndrome or corrected QT interval >500 ms at screening

ECG

18. Inadequately controlled arterial hypertension or prior history of hypertensive crisis

or hypertensive encephalopathy

19. Significant vascular disease including aortic aneurysm requiring surgical repair or

peripheral arterial thrombosis with 6 months prior to randomization

20. History of abdominal or tracheoesophageal fistula or gastrointestinal perforation, or

intra-abdominal abscess within 6 months prior to randomization.

21. 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

22. History of intra-abdominal inflammatory process within 6 months prior to

randomization, including but not limited to peptic ulcer disease, diverticulitis, or

colitis

23. Evidence of bleeding diathesis or significant coagulopathy

24. 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.

25. Uncontrolled tumor-related pain. Patients requiring pain medication must be on a

stable regimen at enrollment.

26. Severe, non healing or dehisced wound, active ulcer, or untreated bone fracture

27. 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

28. Current or recent (within 10 days of randomization) use of acetylsalicyclic acid or

treatment with dipyramidole, ticlopidine, clopidogrel, and cilostazol

29. Current or recent (within 10 days prior to randomization) use of full dose oral or

parenteral anticoagulants or thrombolytic agents for therapeutic purpose.

30. 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.

31. 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

32. Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including

anti-CTLA-4, anti-PD-1, and antiPD-L1 therapeutic antibodies

33. 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

34. 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

35. 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.

36. 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

37. Core biopsy or other minor surgical procedure, excluding placement of a vascular

access device, within 3 days prior to the first dose of bevacizumab

38. Pregnant or breastfeeding females

39. 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.

40. Patient committed to an institution by virtue of an order issued either by the

judicial or the administrative authorities

41. Patient possibly dependent from the investigator including the spouse, children and

close relatives of any investigator

Studien-Rationale

Primary outcome:

1. 24-months survival rate (Time Frame - 24 months):
Percentage of patients alive after 24 months since randomization



Secondary outcome:

1. Median overall survival (mOS) (Time Frame - 24 months):
Defined as the time from treatment initiation until death

2. Progression-free survival (PFS) (Time Frame - 24 months):
Progression is defined according RECIST 1.1 and mRECIST

3. Overall response rate (ORR) (Time Frame - 24 months):
Response is defined by RECIST 1.1 and mRECIST

4. Complete response rate (CRR) (Time Frame - 24 months):
Defined by the percentage of patients with disappearance of tumor manifestation at radiological evaluation

5. Disease control rate (DCR) (Time Frame - 24 months):
Defined as the percentage of patients who have achieved complete response, partial response and stable disease

6. Time to deterioration of liver function (Time Frame - 24 months):
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)

7. Time to untreatable progression (Time Frame - 24 months):
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

8. Time to stage-progression (Time Frame - 24 months):
Defined as time from randomization to disease progression to BCLC C stage

9. Time to first TACE (arm A) (Time Frame - 24 months):
Defined as time from randomization to disease to the first TACE

10. Quality of life (QOL) (Time Frame - 24 months):
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

11. Quality of life (QOL) (Time Frame - 24 months):
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

12. Adverse Events (Time Frame - 24 months):
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0

Studien-Arme

  • Experimental: Up-front Atezo/Bev, then TACE
    Patients 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
  • Experimental: Atezo/Bev combined with TACE
    First 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.

Geprüfte Regime

  • Atezolizumab Injection, Bevacizumab Injection (Chemoembolisation (TACE)):
    Atezolizumab and Bevacizumab will be administered prior to or in combination with TACE

Quelle: ClinicalTrials.gov


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