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
Kontakt:
Phone: +49 89 4400 78160
E-Mail: najib.benkhaled@med.uni-muenchen.de» Kontaktdaten anzeigen
Studienlocations (3 von 7)
KEM Evang. Kliniken Essen Mitte
Essen
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Pluntke Stefan, MD» Ansprechpartner anzeigenUniversity Hospital Jena
07743 Jena
(Thüringen)
GermanyNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Philipp Reuken, MD» Ansprechpartner anzeigenUniversity Hospital Cologne
50931 Köln
(Nordrhein-Westfalen)
GermanyNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Dirk Waldschmidt, MD» Ansprechpartner anzeigen
Essen
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Pluntke Stefan, MD» Ansprechpartner anzeigenUniversity Hospital Jena
07743 Jena
(Thüringen)
GermanyNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Philipp Reuken, MD» Ansprechpartner anzeigenUniversity Hospital Cologne
50931 Köln
(Nordrhein-Westfalen)
GermanyNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Dirk Waldschmidt, MD» Ansprechpartner anzeigen
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 anzeigenKlinikum Rechts der Isar of the Technical University Munich
81675 Munich
(Bayern)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Ursula Ehmer, MD» Ansprechpartner anzeigenUniversity Hospital Regensburg
93053 Regensburg
(Bayern)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Arne Kandulski, MD» Ansprechpartner anzeigenUniversity Hospital Tübingen
72076 Tübingen
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Michael Bitzer, MD» Ansprechpartner anzeigen
Alle anzeigen 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 anzeigenKlinikum Rechts der Isar of the Technical University Munich
81675 Munich
(Bayern)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Ursula Ehmer, MD» Ansprechpartner anzeigenUniversity Hospital Regensburg
93053 Regensburg
(Bayern)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Arne Kandulski, MD» Ansprechpartner anzeigenUniversity Hospital Tübingen
72076 Tübingen
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Michael Bitzer, MD» Ansprechpartner anzeigen
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 Criteria1. 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
