Atezolizumab and Bevacizumab Before Surgery for the Treatment of Resectable Liver Cancer

NCT04721132 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2020-0791NCI-2020-13744
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial studies the effect of atezolizumab and bevacizumab before surgery in treating patients with liver cancer that can be removed by surgery (resectable). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Bevacizumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Giving the combination of atezolizumab and bevacizumab may help to prevent liver cancer from returning after surgery.

Conditions

Resectable Hepatocellular Carcinoma; Stage I Hepatocellular Carcinoma AJCC v8; Stage IA Hepatocellular Carcinoma AJCC v8; Stage IB Hepatocellular Carcinoma AJCC v8; Stage II Hepatocellular Carcinoma AJCC v8

Outcome Measures

Primary Outcomes (2)

• Pathologic complete response (pCR) rate

  Will estimate pCR rate along with the 95% credible interval.

  Up to 2 years post-treatment

• Incidence of adverse events (AEs)

  The AE severity grading scale for the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 will be used for assessing AE severity.

  Up to 30 days post-treatment

Secondary Outcomes (4)

• Objective response rate (ORR)

  At the time of surgery

• Duration of response (DOR)

  From the date of response to the date of recurrence/disease progression, assessed up to 2 years post-treatment

• Recurrence-free survival (RFS)

  From the date of surgery to the date of disease recurrence or death whichever occur first, assessed up to 2 years post-treatment

• Overall survival (OS)

  From the date of treatment start to the date of death or to the date of last follow-up for patients alive, assessed up to 2 years post-treatment

Study Arms (1)

Treatment (atezolizumab, bevacizumab)

EXPERIMENTAL

Patients receive atezolizumab IV over 30-60 minutes and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery during week 12.

Biological: Atezolizumab; Biological: Bevacizumab; Procedure: Therapeutic Conventional Surgery

Interventions

Atezolizumab BIOLOGICAL

Given IV

Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, Tecentriq

Treatment (atezolizumab, bevacizumab)

Bevacizumab BIOLOGICAL

Given IV

Also known as: Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin, Bevacizumab awwb, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Bevacizumab Biosimilar CBT 124, Bevacizumab Biosimilar CT-P16, Bevacizumab Biosimilar FKB238, Bevacizumab Biosimilar GB-222, Bevacizumab Biosimilar HD204, Bevacizumab Biosimilar HLX04, Bevacizumab Biosimilar IBI305, Bevacizumab Biosimilar LY01008, Bevacizumab Biosimilar MIL60, Bevacizumab Biosimilar Mvasi, Bevacizumab Biosimilar QL 1101, Bevacizumab Biosimilar RPH-001, Bevacizumab Biosimilar SCT501, Bevacizumab Biosimilar Zirabev, Bevacizumab-awwb, Bevacizumab-bvzr, BP102, BP102 Biosimilar, HD204, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, Mvasi, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF, SCT501, Zirabev

Treatment (atezolizumab, bevacizumab)

Therapeutic Conventional Surgery PROCEDURE

Undergo surgery

Treatment (atezolizumab, bevacizumab)

Eligibility Criteria

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

You may qualify if:

• Must provide written informed consent prior to initiating any trial related procedures.
• Patient must be ≥ 18 years of age
• Patient has histologically confirmed (if tumor tissue is unavailable, documentation of diagnosis from original biopsy is acceptable) or clinically diagnosed (American Association for the Study of Liver Disease criteria in cirrhotic subjects) hepatocellular carcinoma (HCC).
• Patient has resectable disease with no evidence of extrahepatic spread. The determination of resectability status will ultimately lie in the clinical judgment of the surgical oncologist and medical oncologist involved in the care of the patient.
• Must have a Child-Turcotte-Pugh score of A
• Patients must have at least one measurable site of disease per RECIST version 1.1(Appendix 4) or Immune- Modified RECIST. This is defined as a lesion that can be accurately measured in at least one dimension and measures a minimum of ≥ 10 mm (longest diameter to be recorded) with US, MRI or Spiral CT.
• Patient has record of treated (as necessary per local SoC guidelines) or absent esophageal varices by esophagogastroduodenoscopy within 6 months of initiating treatment.
• Patient must be willing to undergopretreatment research biopsy to provide a tumor sample for exploratory biomarker research.
• ECOG (Eastern Oncology Cooperative Group) performance status 0-1.
• Patient demonstrates adequate organ and marrow function within 14 days of studydrug administration:
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (1500/µL)
• Lymphocyte count ≥ 0.5 × 109/L (500/µL)
• Platelet count ≥ 75 × 109/L (75,000/µL) without transfusion
• Hemoglobin ≥ 90 g/L (9 g/dL)
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase ALP) ≤ 5 × upper limit of normal (ULN)

You may not qualify if:

• Patient has been treated for this malignancy, has another active malignancy, or has had an active malignancy within the last two years.
• Patient has fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
• Patient has had a bleeding event due to untreated esophageal and/or gastric varices.
• Patient has history of abdominal or tracheoesophageal fistula, GI perforation, or intra- abdominal abscess within 6 months of initiation of study treatment.
• Patient has history of thrombosis, bleeding diathesis, History of Grade ≥ 4 venous thromboembolism, coagulopathy or significant vascular disease, serious, non-healing wound, active ulcer, or untreated bone fracture
• Current or recent (\< 10 days prior to initiation of study treatment) use of aspirin (\> 325 mg/day), or clopidogrel (\> 75 mg/day) Note: The use of full-dose oral or parenteral anticoagulants for therapeutic purpose is permitted as long as the INR and/or aPTT is within therapeutic limits (according to institution standards) within 7 days prior to initiation of study treatment and the patient has been on a stable dose of anticoagulants for ≥ 2 weeks prior to initiation of study treatment. Prophylactic use of anticoagulants is allowed. However, the use of direct oral anticoagulant therapies such as dabigatran (Pradaxa) and rivaroxaban (Xarelto) is not recommended due to bleeding risk
• Patient has history of hemoptysis within 30 days of initiation of study treatment.
• Patient has serious cardiac disease, such as New York Heart association Grade II or greater congestive heart failure, MI, unstable angina, etc.
• Patient has inadequately controlled hypertension (systolic ≥ 150 mmHg and/or diastolic ≥ 100 mmHg).
• Patient has significant pulmonary disease (tuberculosis, pneumonia, pneumonitis, etc.).
• Patient requires recurrent drainage procedures (pleural effusion, ascites, etc.).
• Patient has had surgical procedure within 6 weeks of initiation of study treatment.
• Patient has history of central nervous system disease.
• Patient has history of severe allergic/anaphylactic reactions to chimeric or humanized antibodies or fusion proteins.
• Patient has a knownhypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (2)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MDAndersonCancerCenter

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

atezolizumab; Bevacizumab; Immunoglobulin G; Disulfides

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals

Study Officials

• Ahmed O Kaseb

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 7, 2021
• First Posted: January 22, 2021
• Study Start: February 10, 2021
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: March 5, 2026

Record last verified: 2026-03

Locations

US (2)