Detail Article

Informations générales (source: ClinicalTrials.gov)

Numéro NCT

NCT04727307 En recrutement IDF

Titre

Neoadjuvant Atezolizumab and Adjuvant Atezolizumab + Bevacizumab in Combination With Percutaneous Radiofrequency Ablation of Small HCC: a Multicenter Randomized Phase II Trial (AB-LATE02)

Type

Interventional

Pathologie

Carcinome hépatocellulaire

Phase

Phase 2

Promoteur

University Hospital, Montpellier (Voir sur ClinicalTrials)

Date de début

janvier 2021

Date de fin

février 2031

Dernière mise à jour

27 juillet 2024

Résumé

Following the results of study IMbrave150, the combination Atezolizumab + Bevacizumab is a promising treatment option for patients with HCC. In addition, the high intrahepatic distant recurrence rate and accumulating evidence for a metastatic mechanism encourages exploring adjuvant/neoadjuvant strategies targeting tumor growth and metastatic escape in the context of percutaneous thermal ablation for small HCC. Local ablation of HCC is therefore an "ideal" setting for testing atezolizumab + bevacizumab in combination with ablation, with the aim of reducing the risk of recurrence.

Détail

Voir le détail Liver cancer is the sixth most common cancer and the third leading cause of death from cancer worldwide (source: Globocan 2018). Hepatocellular carcinoma (HCC) represents 80-90% of liver cancers. Percutaneous thermal ablation (PTA) is a validated treatment option for very early and early stage HCC, together with surgical resection and liver transplantation (EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma, J Hepatol 2018). Due to its excellent tolerance, particularly in patients with portal hypertension or bearing comorbidities, it now represents in France nearly 70% of the first-line curative treatment of "in Milan" tumours. The risk of local tumor progression (LTP) is ≈10-20% in PTA series (Nault, J Hepatol 2018; N'Kontchou et al., Hepatology (Baltimore, Md) 2009). In addition, the long-term results of PTA are influenced by the high rate (up to 60-80% at 5 years) of intrahepatic distant recurrence (IDR) (Nault et al., J Hepatol 2018), as observed also after HCC surgical resection (EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma, J Hepatol 2018; Imamura et al., J Hepatol 2003). It is unknown whether early IDR (2-3 years after PTA of <3 cm HCC) is due to metastatic spread or de novo carcinogenesis. Strong scientific rationale and emerging clinical data suggest that the combined vascular endothelial growth factor (VEGF) / Programmed death-ligand 1 (PD-L1) blockade may be clinically beneficial in a number of tumor types, including HCC. Therefore, local ablation in HCC is an " ideal " context to test Atezolizumab + Bevacizumab in combination with ablation. The investigators hypothesized that the combo of Atezolizumab + Bevacizumab and radiofrequency ablation could improve recurrence-free survival (RFS) at 2 years. The aim of this randomized multicentre phase II trial is to compare RFS at 2 years in the experimental arm (Atezolizumab + Bevacizumab + RF ablation) versus the control arm (RF ablation) according to HCC modified response evaluation criteria in solid tumours (mRECIST). Thus the proposed use here of Atezolizumab as first neoadjuvant, then in combination with Bevacizumab as adjuvants, should theoretically, and hopefully, limit the radiofrequency ablation (RFA) pro-tumor effects. The RFS current rate value of 45% corresponding to the standard procedure of RFA alone (i.e. in the Active Comparator arm) should be increasing to at least 65% because of the addition of the biotherapy (i.e. in the Experimental arm). The patients' recruitment timeframe is set at 36 months and the patient's follow-up timeframe is 5 years. 202 patients are to be included, 101 per arm. Fermer le détail

Etablissements

Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données
CLCC INSTITUT GUSTAVE ROUSSY	Thierry DE BAERE	Recrutement non commencé	16/04/2024 07:02:31	Contacter
Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données
AP-HP - Hôpital Beaujon	Maxime RONOT, MD	En recrutement IDF		Contact (sur clinicalTrials)
AP-HP - Hôpital Cochin	Anthony DOHAN, MD	En recrutement IDF		Contact (sur clinicalTrials)
AP-HP - Hôpital Jean Verdier	Pierre NAHON, MD	En recrutement IDF		Contact (sur clinicalTrials)
Les établissements hors Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données
CH Perpignan - Perpignan - France	Faiza KHEMISSA, MD	En recrutement		Contact (sur clinicalTrials)
CHRU de Nancy - Nancy - France	Valérie CROISE-LAURENT, MD	En recrutement		Contact (sur clinicalTrials)
CHU d'Angers - Angers - France	Jérôme LEBIGOT, MD	En recrutement		Contact (sur clinicalTrials)
CHU de Nice - Nice - France	Patrick CHEVALLIER, MD	Recrutement non commencé		Contact (sur clinicalTrials)
CHU de Poitiers - Poitiers - France	Jean-Pierre TASU, MD	En recrutement		Contact (sur clinicalTrials)
CHU de Rennes - Rennes - France	Vanessa BRUN, MD	En recrutement		Contact (sur clinicalTrials)
Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données
Centre Georges François Leclerc - Dijon - France	François GHIRINGHELLI, MD	En recrutement		Contact (sur clinicalTrials)
CHU Amiens - Amiens - France	Eric NGUYEN-KHAC, MD	En recrutement		Contact (sur clinicalTrials)
CHU de Grenoble - Grenoble - France	Thomas DECAENS, MD	En recrutement		Contact (sur clinicalTrials)
CHU de Lille - Lille - France	Géraldine SERGENT, MD	Recrutement non commencé		Contact (sur clinicalTrials)
CHU de Montpellier - Montpellier - France	Boris GUIU, MD, PhD	En recrutement		Contact (sur clinicalTrials)
CHU de Nantes - Nantes - France	Yann TOUCHEFFEU, MD	En recrutement		Contact (sur clinicalTrials)
CHU Dijon - Dijon - France	Romaric LOFFROY, MD	En recrutement		Contact (sur clinicalTrials)
CHU Nîmes - Nîmes - France	Julien FRANDON, MD	En recrutement		Contact (sur clinicalTrials)
Hôpital Saint Joseph - Marseille - France		En recrutement		Contact (sur clinicalTrials)

Critères

Genre

Tous

Nombre d'inclusion

Critère d'inclusion

Inclusion Criteria:

1. Male or female patients ≥ 18 years of age

2. Diagnostic of HCC based on Imaging (EASL guidelines)

3. Patients with HCC eligible for ablation as assessed by multidisciplinary board:

- All HCC nodules <3cm

- 1-3 nodules of HCC

4. At least one uni-dimensional measurable lesion by magnetic resonance imaging (MRI)
according to modified RECIST criteria

5. Liver function status Child-Pugh Class A

6. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1

7. Adequate bone marrow, liver and renal function as assessed by the following
laboratory tests:

- Hemoglobin > 8.5 g/dL

- Absolute neutrophil count ≥ 1500/mm3

- Platelet count ≥ 50,000/ mm3

- Total bilirubin ≤ 2 mg/dL (ou ≤ 34 µmol/ L).

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x upper
limit of normal (ULN)

- Serum creatinine ≤ 1.5 x ULN

- Lipase ≤ 2 x ULN

- Prothrombin time > 50%

- Glomerular Filtration Rate (GFR) ≥ 35 mL/min/1.73 m2

8. Life expectancy ≥ 3 months

9. Women of childbearing potential and men must agree to use adequate contraception

10. Patients affiliated to a Social Security System

Critère de non inclusion

1. Patients with contraindications to ablation or atezolizumab or bevacizumab

2. Patients with contraindication to contrast medium intravenous injection either
gadolinium or iodinate

3. Patients with contraindication to MRI

4. Prior liver transplantation

5. Child-Pugh B or C

6. Patients with mixed histology (HCC and cholangiocarcinoma, namely
hepatocholangiocarcinoma), if a biopsy is available

7. Current or recent (≤ 10 days prior to initiation of study treatment) use of
full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic
(as opposed to prophylactic) purpose. Prophylactic anticoagulation for the patency
of venous access devices is allowed provided the activity of the agent results in an
INR < 1.5 x ULN and aPTT is within normal limits within 14 days prior to initiation
of study treatment. For prophylactic use of anticoagulants or thrombolytic
therapies, the approved dose as described by local label may be used.

8. Current or recent (≤10 days prior to initiation of study treatment) use of aspirin
(> 325 mg/day) or treatment with clopidogrel, dipyramidole, ticlopidine, or
cilostazol.

9. Active or history of autoimmune disease or immune deficiency, including, but not
limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus
erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid
antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré
syndrome, or multiple sclerosis, with the following exceptions:

1. Patients with a history of autoimmune-related hypothyroidism who are on
thyroid-replacement hormone are eligible for the study.

2. Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen
are eligible for the study.

3. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with
dermatologic manifestations only (e.g., patients with psoriatic arthritis are
excluded) are eligible for the study provided all of following conditions are
met:

- Rash must cover < 10% of body surface area.

- Disease is well controlled at baseline and requires only low-potency
topical corticosteroids.

- No occurrence of acute exacerbations of the underlying condition requiring
psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic
agents, oral calcineurin inhibitors, or high-potency or oral
corticosteroids.

10. Treatment with systemic immunosuppressive medication (including, but not limited to,
corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and
anti-TNF-α agents) within 2 weeks prior to initiation of study treatment, or
anticipation of need forsystemic immunosuppressive medication during study
treatment, with the following exceptions:

- Patients who received acute, low-dose systemic immunosuppressant medication or
a onetime pulse dose of systemic immunosuppressant medication (e.g., 48 hours
of corticosteroids for a contrast allergy) are eligible for the study after
Medical Monitor confirmation has been obtained.

- Patients who received mineralocorticoids (e.g., fludrocortisone),
corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or
low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency
are eligible for the study.

11. Portal vein invasion, whatever its extent, shown on baseline imaging

12. Prior chemo-embolization or radio-embolization.

13. Patients with extra-hepatic metastases, either previously-treated or not. One lung
nodule (<5mm) is allowed. Calcified lung micronodules as well as typical
intra-pulmonary lymph nodes are allowed. Hepatic hilum lymph node < 10mm (short
axis) is allowed.

14. Prior surgery of HCC with micro- or macro-vascular invasion demonstrated at
pathology.

15. Prior systemic treatment for HCC, in particular agents targeting T-cell
costimulation or checkpoint pathways (including those targeting PD-1, PD-L1 or
PD-L2, cluster of differentiation 137 (CD137), or cytotoxic T-lymphocyte antigen
(CTLA-4)).

16. Patients with uncontrolled HBV infection and viral load above 500 IU/mL.

17. Untreated or incompletely treated esophageal and/or gastric varices with bleeding or
high risk for bleeding. Patients must undergo an esophagogastroduodenoscopy (EGD),
and all size of varices (small to large) must be assessed and treated per local
standard of care prior to enrollment. Patients who have undergone an EGD within 6
months of prior to initiation of study treatment do not need to repeat the procedure

18. Past or concurrent history of neoplasm other than HCC, except for in-situ carcinoma
of the cervix uteri and/or non-melanoma skin cancer and superficial bladder tumors.
Any cancer curatively treated > 3 years prior to study entry is permitted

19. Known history or symptomatic meningeal tumors

20. Grade 3 (severe) hypertension ≥160 and/or ≥100 mmHG (systolic and diastolic,
according to NCI-CTCAE v5.0)

21. Patients with phaeochromocytoma

22. Ongoing infection : Hepatitis B is allowed if no active replication is present (HBV
replication below 500 IU/mL) or Hepatitis C is allowed if no antiviral treatment is
required

23. Clinically significant bleeding NCI-CTCAE version 5.0 ≥ Grade 3 within 30 days
before enrolment (transfusion indicated)

24. Arterial or venous thrombotic or embolic events such as cerebrovascular accident,
deep vein thrombosis or pulmonary embolism within 6 months before enrolment

25. Any psychological, familial, sociological, geographical or illness or medical
condition that could jeopardize the safety of the patient and/or his compliance with
the study protocol and follow-up procedure

26. Known history of human immunodeficiency virus (HIV) infection

27. Seizure disorder requiring medication

28. Non-healing wound, ulcer or bone fracture

29. Breast feeding

30. Pregnancy

31. Legal incapacity (persons in custody or under guardianship)

32. Deprived of liberty Subject (by judicial or administrative decision)

NCT04727307 - Neoadjuvant Atezolizumab and Adjuvant Atezolizumab + Bevacizumab in Combination With Percutaneous Radiofrequency Ablation of Small HCC: a Multicenter Randomized Phase II Trial (AB-LATE02)

Informations générales
Etablissements
Critères
Accès à la fiche NCT

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