A Study to Determine Whether Chemotherapy and Atezolizumab is Better Than Chemotherapy, Bevacizumab and Atezolizumab in Patients With Advanced Liver Cancer

NCT05211323 | Active Not Recruiting Phase 2 FDA Drug

• 3 other identifiers: NCI-2022-00151EA2205U10CA180820
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 37

Brief Summary

This phase II trial compares the effect of adding bevacizumab and atezolizumab to gemcitabine and cisplatin (chemotherapy) versus chemotherapy and atezolizumab in treating patients with liver cancer that cannot be removed by surgery (unresectable) or that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). 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 in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Chemotherapy drugs, such as gemcitabine and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving bevacizumab and atezolizumab with chemotherapy may kill more tumor cells in patients liver cancer than chemotherapy and atezolizumab.

Conditions

Stage III Liver Cancer; Stage IV Liver Cancer; Combined Hepatocellular Carcinoma and Cholangiocarcinoma

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  Defined as time to progressive disease or death due to any cause as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. The null hypothesis of equality of PFS will be tested using a one-sided alternative favoring the quadruplet arm. The primary comparison will be via a one-sided log rank test.

  From start of treatment until progression, assessed up to 3 years

Secondary Outcomes (2)

• Objective response rate

  Up to 3 years

• Overall response rate

  Up to 3 years

Study Arms (2)

Arm A (atezolizumab, bevacizumab, gemcitabine, cisplatin)

EXPERIMENTAL

Patients receive atezolizumab IV over 30-60 minutes on day 1, bevacizumab IV over 30-90 minutes on day 1, gemcitabine IV over 30 minutes on days 1 and 8, and cisplatin IV on days 1 and 8. Cycles repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI throughout the trial. Patients undergo blood specimen collection on study.

Biological: Atezolizumab; Biological: Bevacizumab; Procedure: Biospecimen Collection; Drug: Cisplatin; Procedure: Computed Tomography; Procedure: Conventional Magnetic Resonance Imaging; Drug: Gemcitabine Hydrochloride

Arm B (atezolizumab, gemcitabine, cisplatin)

ACTIVE COMPARATOR

Patients receive atezolizumab IV over 30-60 minutes on day 1, and gemcitabine IV over 30 minutes and cisplatin IV on days 1 and 8. Cycles repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT or magnetic resonance imaging MRI throughout the trial. Patients undergo blood specimen collection on study.

Biological: Atezolizumab; Procedure: Biospecimen Collection; Drug: Cisplatin; Procedure: Computed Tomography; Procedure: Conventional Magnetic Resonance Imaging; Drug: Gemcitabine Hydrochloride

Interventions

Atezolizumab BIOLOGICAL

Given IV

Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG 7446, RG-7446, RG7446, RO 5541267, RO-5541267, RO5541267, Tecentriq

Arm A (atezolizumab, bevacizumab, gemcitabine, cisplatin); Arm B (atezolizumab, gemcitabine, cisplatin)

Bevacizumab BIOLOGICAL

Given IV

Also known as: ABP 215, ABP-215, ABP215, Alymsys, Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF Monoclonal Antibody SIBP04, Anti-VEGF rhuMAb, Avastin, Avzivi, Aybintio, BAT 1706, BAT-1706, BAT1706, BAT1706 Biosimilar, Bevacizumab awwb, Bevacizumab Biosimilar ABP 215, Bevacizumab Biosimilar BAT1706, 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 MB02, Bevacizumab Biosimilar MIL60, Bevacizumab Biosimilar Mvasi, Bevacizumab Biosimilar MYL-1402O, Bevacizumab Biosimilar QL 1101, Bevacizumab Biosimilar QL1101, Bevacizumab Biosimilar RPH-001, Bevacizumab Biosimilar SCT501, Bevacizumab Biosimilar Zirabev, Bevacizumab-adcd, Bevacizumab-awwb, Bevacizumab-aybi, Bevacizumab-bvzr, Bevacizumab-equi, Bevacizumab-maly, Bevacizumab-onbe, Bevacizumab-tnjn, BP102, BP102 Biosimilar, CT P16, CT-P16, CTP16, Equidacent, FKB 238, FKB-238, FKB238, 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, MB 02, MB-02, MB02, Mvasi, MYL-1402O, Onbevzi, Oyavas, PF 06439535, PF-06439535, PF06439535, QL1101, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF, SCT501, SIBP 04, SIBP-04, SIBP04, Vegzelma, Zirabev

Arm A (atezolizumab, bevacizumab, gemcitabine, cisplatin)

Biospecimen Collection PROCEDURE

Undergo blood specimen collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm A (atezolizumab, bevacizumab, gemcitabine, cisplatin); Arm B (atezolizumab, gemcitabine, cisplatin)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Arm A (atezolizumab, bevacizumab, gemcitabine, cisplatin); Arm B (atezolizumab, gemcitabine, cisplatin)

Gemcitabine Hydrochloride DRUG

Given IV

Also known as: dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemcitabine HCI, Gemzar, LY 188011, LY-188011, LY188011

Arm A (atezolizumab, bevacizumab, gemcitabine, cisplatin); Arm B (atezolizumab, gemcitabine, cisplatin)

Cisplatin DRUG

Given IV

Also known as: Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin

Arm A (atezolizumab, bevacizumab, gemcitabine, cisplatin); Arm B (atezolizumab, gemcitabine, cisplatin)

Conventional Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Conventional MRI

Arm A (atezolizumab, bevacizumab, gemcitabine, cisplatin); Arm B (atezolizumab, gemcitabine, cisplatin)

Eligibility Criteria

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

You may qualify if:

• Patient must be \>= 18 years of age
• Patient must have a histologically confirmed diagnosis of combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CC) at the local laboratory based on the 2019 World Health Organization (WHO) classification, including the classical type and intermediate cell carcinoma
• The classical type defines primary liver carcinoma with unequivocal features of both HCC and CC differentiation within the same tumors on routine histopathology with hematoxylin and eosin stains regardless of the proportion of each histology observed
• The intermediate cell carcinoma defines cancers with biphenotypic differentiation in which cells have a morphology intermediate between hepatocytes and cholangiocytes. Intermediate cell carcinoma may be associated with expression of both hepatocyte and cholangiocytic markers. Distinct HCC and CC arising in the same liver, fibrolamellar HCC, morphologically typical HCCs with only immunohistochemical expression of keratin or other cholangiocytic markers, or morphologically typical CCs with only immunohistochemical expression of hepatocytic markers will be excluded
• NOTE: Local pathology review constitutes adequate documentation of histology for initial study enrollment and treatment
• Patient must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Patient must have disease which is unresectable or metastatic
• Patient must not have any prior history of systemic therapy for advanced cHCC-CC. Prior adjuvant treatment composed of chemotherapy agents such as capecitabine or gemcitabine-based treatments are allowed if adjuvant treatment if at least 6 months have elapsed since completing chemotherapy at the time of enrollment
• Patient must be Child Pugh class A
• Patients with prior locoregional therapy are eligible provided the following are met:
• Prior loco-regional therapy including surgical resection, chemoembolization, radiotherapy, or ablation was completed \> 4 weeks prior to randomization
• Treated target lesion has increased in size by \> 25% or the target lesion was not treated with loco-regional therapy
• Patients treated with palliative radiotherapy for symptoms must have completed radiotherapy \> 7 days prior to randomization and the target lesion must not have been the treated lesion
• Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used.
• All patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (37)

Sutter Auburn Faith Hospital

Auburn, California, 95602, United States

Location

Alta Bates Summit Medical Center-Herrick Campus

Berkeley, California, 94704, United States

Location

Palo Alto Medical Foundation-Fremont

Fremont, California, 94538, United States

Location

Memorial Medical Center

Modesto, California, 95355, United States

Location

Palo Alto Medical Foundation-Camino Division

Mountain View, California, 94040, United States

Location

Palo Alto Medical Foundation Health Care

Palo Alto, California, 94301, United States

Location

Sutter Roseville Medical Center

Roseville, California, 95661, United States

Location

Sutter Medical Center Sacramento

Sacramento, California, 95816, United States

Location

California Pacific Medical Center-Pacific Campus

San Francisco, California, 94115, United States

Location

Palo Alto Medical Foundation-Santa Cruz

Santa Cruz, California, 95065, United States

Location

Palo Alto Medical Foundation-Sunnyvale

Sunnyvale, California, 94086, United States

Location

Sutter Solano Medical Center/Cancer Center

Vallejo, California, 94589, United States

Location

Carle at The Riverfront

Danville, Illinois, 61832, United States

Location

Carle Physician Group-Effingham

Effingham, Illinois, 62401, United States

Location

Carle Physician Group-Mattoon/Charleston

Mattoon, Illinois, 61938, United States

Location

Carle Cancer Center

Urbana, Illinois, 61801, United States

Location

The Carle Foundation Hospital

Urbana, Illinois, 61801, United States

Location

Memorial Hospital of South Bend

South Bend, Indiana, 46601, United States

Location

UI Health Care Mission Cancer and Blood - Ankeny Clinic

Ankeny, Iowa, 50023, United States

Location

Iowa Methodist Medical Center

Des Moines, Iowa, 50309, United States

Location

UI Health Care Mission Cancer and Blood - Des Moines Clinic

Des Moines, Iowa, 50309, United States

Location

Mercy Medical Center - Des Moines

Des Moines, Iowa, 50314, United States

Location

Miami Valley Hospital South

Centerville, Ohio, 45459, United States

Location

Miami Valley Hospital

Dayton, Ohio, 45409, United States

Location

Premier Blood and Cancer Center

Dayton, Ohio, 45409, United States

Location

Miami Valley Hospital North

Dayton, Ohio, 45415, United States

Location

Atrium Medical Center-Middletown Regional Hospital

Franklin, Ohio, 45005-1066, United States

Location

Miami Valley Cancer Care and Infusion

Greenville, Ohio, 45331, United States

Location

Upper Valley Medical Center

Troy, Ohio, 45373, United States

Location

Parkland Memorial Hospital

Dallas, Texas, 75235, United States

Location

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States

Location

UT Southwestern/Simmons Cancer Center-Fort Worth

Fort Worth, Texas, 76104, United States

Location

UT Southwestern Clinical Center at Richardson/Plano

Richardson, Texas, 75080, United States

Location

VCU Massey Cancer Center at Stony Point

Richmond, Virginia, 23235, United States

Location

VCU Massey Comprehensive Cancer Center

Richmond, Virginia, 23298, United States

Location

Marshfield Medical Center-EC Cancer Center

Eau Claire, Wisconsin, 54701, United States

Location

Marshfield Medical Center - Minocqua

Minocqua, Wisconsin, 54548, United States

Location

MeSH Terms

Conditions

Liver Neoplasms

Interventions

atezolizumab; Bevacizumab; Immunoglobulin G; Disulfides; Specimen Handling; Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; Platinum; Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; 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; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Chlorine Compounds; Nitrogen Compounds; Platinum Compounds; Metals, Heavy; Elements; Transition Elements; Metals; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• David Hsieh

  ECOG-ACRIN Cancer Research Group

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 22, 2022
• First Posted: January 27, 2022
• Study Start: December 7, 2022
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

US (37)