Clinical Trials /

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

NCT04721132

Description:

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.

Related Conditions:
  • Hepatocellular Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Atezolizumab and Bevacizumab Before Surgery for the Treatment of Resectable Liver Cancer
  • Official Title: An Open-Label, Phase II, Pre-Operative Study of Atezolizumab Plus Bevacizumab for Resectable Hepatocellular Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: 2020-0791
  • SECONDARY ID: NCI-2020-13744
  • SECONDARY ID: 2020-0791
  • NCT ID: NCT04721132

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

Interventions

DrugSynonymsArms
AtezolizumabMPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, TecentriqTreatment (atezolizumab, bevacizumab)
BevacizumabAnti-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 QL 1101, Bevacizumab Biosimilar RPH-001, Bevacizumab Biosimilar SCT501, 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, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF, SCT501Treatment (atezolizumab, bevacizumab)

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate safety and tolerability of atezolizumab plus bevacizumab combination therapy
      in the pre-operative setting.

      II. To assess the rate of pathologic complete response.

      SECONDARY OBJECTIVE:

      I. To evaluate the correlation between rate of pathologic complete response, overall response
      rate at time of surgery (per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 and
      modified RECIST 1.0), duration of response as defined by time to recurrence/recurrence-free
      survival, in addition to overall survival.

      EXPLORATORY OBJECTIVES:

      I. To evaluate the predictive value of dynamic changes in fibrosis stage (defined by a
      minimum 1-point improvement in fibrosis stage 0-4 per magnetic resonance elastography [MRE])
      and in IGF-1 blood score.

      II. To measure baseline and longitudinal changes of immune infiltration including
      CD8/regulatory T cell (Treg) ratio and CD68+ density, and fibrosis stage by MRE for up to one
      year.

      OUTLINE:

      Patients receive atezolizumab intravenously (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.

      After completion of study treatment, patients are followed up every 3 months for 2 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (atezolizumab, bevacizumab)ExperimentalPatients 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.
  • Atezolizumab
  • Bevacizumab

Eligibility Criteria

        Inclusion Criteria:

          -  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 based on the following tumor parameters: one single tumor =< 5 cm,
                  or largest tumor =< 5 cm and =< 3 tumors without vascular invasion on imaging

          -  Must have a Child-Turcotte-Pugh score A

          -  Must have measurable disease defined as a lesion that can be accurately measured in at
             least one dimension (longest diameter to be recorded) and that measures >= 10 mm with
             ultrasound (US), magnetic resonance imaging (MRI) or spiral computed tomography (CT)
             scan

          -  Patient has record of treated or absence of esophageal varices by
             esophagogastroduodenoscopy within 6 months of initiating treatment

          -  Patient must be have a representative tumor specimen or be willing to undergo research
             biopsy and provide tumor sample for exploratory biomarker research

          -  ECOG (Eastern Oncology Cooperative Group) performance status >= 1

          -  Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (1500/uL) (within 14 days of study
             drug administration)

          -  Lymphocyte count >= 0.5 x 10^9/L (500/uL) (within 14 days of study drug
             administration)

          -  Platelet count >= 100 x 10^9/L (100,000/uL) without transfusion (within 14 days of
             study drug administration)

          -  Hemoglobin >= 90 g/L (9 g/dL) (within 14 days of study drug administration)

          -  Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline
             phosphatase (ALP) =< 2.5 x upper limit of normal (ULN) (within 14 days of study drug
             administration)

          -  Serum bilirubin =< 1.5 x ULN (within 14 days of study drug administration) with the
             following exception:

               -  Patients with known Gilbert disease: serum bilirubin =< 3 x ULN

          -  Serum creatinine =< 1.5 x ULN (within 14 days of study drug administration)

          -  Serum albumin >= 25 g/L (2.5 g/dL) (within 14 days of study drug administration)

          -  International normalized ratio (INR) or activated partial thromboplastin time (aPTT)
             =< 1.5 x ULN (within 14 days of study drug administration)

          -  Negative human immunodeficiency virus (HIV) test at screening (within 14 days of study
             drug administration)

          -  Urinalysis (UA) with protein less than 2+ (within 14 days of study drug
             administration)

          -  Documented virology status of hepatitis, as confirmed by screening hepatitis B virus
             (HBV) and hepatitis C virus (HCV) tests (within 14 days of study drug administration)

               -  For patients with active HBV: HBV deoxyribonucleic acid (DNA) < 500 IU/mL during
                  screening, initiation of anti-HBV treatment at least 14 days prior to
                  randomization and willingness to continue anti-HBV treatment during the study
                  (per local standard of care; e.g., entecavir)

          -  Women of childbearing potential (WOCBP) and men with partners of child bearing
             potential agree to prevent pregnancy using two forms of contraception from the date of
             informed consent through 5 months post last dose of study drug

          -  Women of child bearing potential must have a negative serum pregnancy test result
             within 14 days of initiating study treatment

          -  Women of child bearing potential must not be breastfeeding

        Exclusion Criteria:

          -  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, gastrointestinal (GI)
             perforation, or intra-abdominal abscess within 6 months of initiation of study
             treatment

          -  Patient has history of thrombosis, bleeding diathesis, coagulopathy or significant
             vascular disease

          -  Patient has history of hemoptysis within 30 days of initiation of study treatment

          -  Patient has serious cardiac disease, including New York Heart Association grade II or
             greater congestive heart failure, myocardial infarction (MI), unstable angina, etc

          -  Patient has inadequately controlled hypertension (systolic >= 150 mmHg and/or
             diastolic >= 100 mmHg)

          -  Patient has significant pulmonary disease including tuberculosis, pneumonia,
             pneumonitis, etc

          -  Patient requires recurrent drainage procedures including 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 known hypersensitivity to Chinese hamster ovary cell products or to any
             component of the atezolizumab formulation

          -  Patient has known hypersensitivity to bevacizumab

          -  Patient has had any investigational agents within 28 days prior to initiation of study
             treatment

          -  Patient has history of severe infection within 4 weeks of initiation of treatment

          -  Patient has history of auto immune disease or auto immune deficiency

          -  Patient has received stem cell transplantation, liver transplantation, or solid organ
             transplantation

          -  Patient has history of other significant comorbidities that would be contraindicated
             for investigational treatment

          -  Patient has used:

               -  High dose steroids

               -  Vaccine of any kind within 4 weeks of initiating study treatment

               -  Oral or IV antibiotics within 2 weeks of initiating study treatment

               -  Immunostimulatory agents within 4 weeks of initiating study treatment

               -  Anticoagulation therapy (aspirin permitted)

               -  Total parenteral nutrition

          -  Patient is pregnant or breastfeeding
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Pathologic complete response (pCR) rate
Time Frame:Up to 2 years post-treatment
Safety Issue:
Description:Will estimate pCR rate along with the 95% credible interval.

Secondary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:At the time of surgery
Safety Issue:
Description:Objective response is defined as complete response or partial response, per Response Evaluation Criteria in Solid Tumors (RECIST 1.1), modified (m)RECIST1.0. ORR will be summarized along with 95% confidence intervals. Fisher's exact test will be used to correlate pCR and OR.
Measure:Duration of response (DOR)
Time Frame:From the date of response to the date of recurrence/disease progression, assessed up to 2 years post-treatment
Safety Issue:
Description:DOR will be estimated with the Kaplan-Meier methods.
Measure:Recurrence-free survival (RFS)
Time Frame:From the date of surgery to the date of disease recurrence or death whichever occur first, assessed up to 2 years post-treatment
Safety Issue:
Description:RFS will be estimated with the Kaplan-Meier methods. The log-rank test will be used to evaluate the association between pCR and RFS.
Measure:Overall survival (OS)
Time Frame: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
Safety Issue:
Description:OS will be estimated with the Kaplan-Meier methods. The log-rank test will be used to evaluate the association between pCR and OS.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated

January 22, 2021