Study to Evaluate the Efficacy and Safety of Atezolizumab and Bevacizumab as Neoadjuvant Plus Adjuvant Treatment in HCC

NCT07018947 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 2025-521459-22-00
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 13

Brief Summary

Study to evaluate the efficacy and safety of the combination of Atezolizumab and Bevacizumab as neoadjuvant plus adjuvant treatment in Hepatocellular Carcinoma.

Conditions

Resectable Hepatocellular Carcinoma

Keywords

resectable HCC with high risk of recurrence

Outcome Measures

Primary Outcomes (1)

• Recurrence-free survival (RFS)

  Measured by RFS, defined as the time from randomization to the first documented recurrence of disease according to RECIST v1.1 and mRECIST by the investigator's radiology team, or death from any cause (whichever occurs first).

  From randomization to the first documented recurrence of disease or death from any cause, whichever occurs first, assessed up to 5 years.

Secondary Outcomes (13)

• Pathological response

  Surgery

• Pathological response

  Surgery

• Overall Survival (OS)

  From randomization to death from any cause, assessed up to 5 years.

• Efficacy of neoadjuvant with atezolizumab plus bevacizumab treatment combinations

  From randomization to predefined event or death, whichever came first, assessed up to 5 years.

• Efficacy of neoadjuvant with atezolizumab plus bevacizumab treatment combinations

  Pre-Surgery visit

Study Arms (2)

Atezolizumab and Bevacizumab

EXPERIMENTAL

Participants in the atezolizumab plus bevacizumab (Atezo + Bev) arm will receive up to three 3 atezolizumab doses (days 10, 31, 52) and 2 bevacizumab dose (days 10 and 31) until surgery or unacceptable toxicity, whichever occurs first (neoadjuvant therapy). The adjuvant therapy with Atezo + Bev will start between 4 and 12 weeks after the resection date, once the participant has fully recovered from the surgery. Participants will receive up to 12 months or 17 cycles of treatment, whichever occurs first, or until disease recurrence or unacceptable toxicity.

Drug: Atezolizumab and Bevacizumab

Survillance

NO INTERVENTION

In Arm Survillance, participants will receive standard of care with no neoadjuvant and adjuvant treatment, undergo surgical resection.

Interventions

Atezolizumab and Bevacizumab DRUG

Participants will receive up to three 3 atezolizumab doses (days 10, 31, 52) and 2 bevacizumab dose (days 10 and 31) until surgery or unacceptable toxicity, whichever occurs first (neoadjuvant therapy). The adjuvant therapy with Atezo + Bev will start between 4 and 12 weeks after the resection date, once the participant has fully recovered from the surgery. Participants will receive up to 12 months or 17 cycles of treatment, whichever occurs first, or until disease recurrence or unacceptable toxicity.

Atezolizumab and Bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Informed Consent Form.
• Age ≥ 18 years at the time of signing Informed Consent Form.
• Ability to fully comply with the protocol, in the investigator's judgment.
• Diagnosis of HCC confirmed by histology.
• HCC that is amenable to R0 surgical resection with curative intent in the opinion of the surgeons and oncologists or hepatologists involved in the care of the participant.
• HCC at high-risk of recurrence defined by either multifocality, large tumor diameter (\>5cm), AFP (alpha-fetoprotein) ≥400ng/mL, poor tumor differentiation, or the presence of microvascular invasion.
• \- For patients with tumors between 3-5 cm, a predefined nomogram will be applied, indicating a high prevalence of microvascular invasion with a score \>200 points. (Lie et al., 2016).
• Measurable disease (at least one target lesion) according to RECIST v1.1 as determined by the investigator.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0.
• Child-Pugh Class A.
• No evidence of clinically significant portal hypertension (CSPH) or minor CSPH (HVPG \<12 mmHg) in candidates for minor resection (fewer than 3 segments). (Galle et al., 2018) Clinically significant portal hypertension (CSPH) can be defined either by its gold standard measurement, a hepatic venous pressure gradient (HVPG) ≥10 mmHg, or by the presence of surrogate markers such as a platelet count \<100,000 × 10³/µL combined with splenomegaly.
• Willing to undergo a tumor biopsy at screening visit.
• \- Baseline tumor tissue samples will be collected from all participants by means of a core-needle biopsy performed at study entry. A minimum of two core-needle biopsies are required. If a fresh biopsy is not deemed feasible by the investigator, archival tumor tissue may be submitted, provided the tissue was obtained from a biopsy performed within 3 months prior to enrollment and the patient has not received any anti-cancer therapy, including locoregional liver-directed therapy, since the time of the biopsy. Tumor and normal adjacent tissue specimen will be collected at surgery as fresh snap-frozen and formalin-fixed, paraffin-embedded (FFPE) format. FFPE tissue blocks are preferred, or a minimum of 20 slides must be submitted.
• No prior locoregional or systemic treatment for HCC.
• Adequate hematologic and end-organ function, defined by the following laboratory test results:

You may not qualify if:

• Presence of extrahepatic disease or macrovascular invasion.
• Known fibrolamellar HCC, sarcomatoid HCC, mixed cholangiocarcinoma and HCC, or other rare variants of HCC.
• History of hepatic encephalopathy if clinically significant within one year prior to screening.
• CSPH in candidates for major resection (more than 3 segments).
• Moderate or severe ascites.
• Active co-infection with HBV and HCV (defined as detectable HCV RNA plus positive HBV surface antigen or HBV DNA). Patients with a history of HCV infection but who are negative for HCV RNA by Polymerase Chain Reaction (PCR) will be considered non-infected with HCV.
• Known active co-infection with HBV and hepatitis D viral infection (HDV).
• Prior treatment with immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies.
• Treatment with investigational therapy within 28 days prior to screening.
• Untreated or incompletely treated esophageal and/or gastric varices with bleeding or that are at high risk for bleeding. Participants 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. Participants who have undergone an EGD within 6 months prior screening do not need to repeat the procedure.
• A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to screening.
• Inadequately controlled hypertension, defined as systolic blood pressure (BP) \> 150 mmHg and/or diastolic BP \> 100 mmHg (average of at least three readings at two or more sessions).
• \- Anti-hypertensive therapy to achieve these parameters is allowed.
• History of hypertensive crisis or hypertensive encephalopathy.
• Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to screening.

Sponsors & Collaborators

• Fundacion Clinic per a la Recerca Biomédica: lead

Study Sites (13)

Complejo Hospitalario Universitario de Santiago de Compostela

Santiago de Compostela, A Coruña, 15706, Spain

Location

Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Hospital Universitari de Bellvitge

Barcelona, Barcelona, 08907, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, Barcelona, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Hospital Universitario Reina Sofía

Córdoba, Cordoba, 14004, Spain

Location

Hospital Universitari Josep Trueta

Girona, Girona, 17007, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, Madrid, 28007, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, Madrid, 28034, Spain

Location

Hospital Universitario Fundación Jiménez Díaz

Madrid, Madrid, 28040, Spain

Location

Hospital Universitario Virgen de la Victoria

Puerto de la Torre, Málaga, 29010, Spain

Location

Hospital Universitario y Politécnico La Fe

Valencia, Valencia, 46026, Spain

Location

Hospital Universitario de Cruces

Barakaldo, Vizcaya, 48903, Spain

Location

MeSH Terms

Interventions

atezolizumab; Bevacizumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Ezequiel Matias Mauro

CONTACT

+34 932275400; mauro@recerca.clinic.cat

Eva Bonfill Vernet

CONTACT

+34 932275400 Ext. 4198; bonfill@recerca.clinic.cat

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2025
• First Posted: June 13, 2025
• Study Start: November 1, 2025
• Primary Completion (Estimated): November 1, 2030
• Study Completion (Estimated): November 1, 2030
• Last Updated: June 13, 2025

Record last verified: 2025-06

Locations

ES (13)