Atezolizumab and Bevacizumab in Combination With TACE for Patients With BCLC B HCC

NCT05776875 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2000026840000
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

There is an unmet need for patients with intermediate stage hepatocellular carcinoma (HCC). It is known that local tumor ablation can increase tumor immunogenicity by releasing tumor associated antigens, potentially increasing the response to immune therapy not just locally, but systemically. In addition, there is now positive data with immune therapy in advanced HCC, there is renewed interest in the combination of local therapy and systemic therapy in Barcelona Clinic Liver Clinic B (BCLC B) patients with systemic therapies other than sorafenib. Based on this data, the investigators plan to examine the atezolizumab and bevacizumab combination with Transarterial Chemoembolization (TACE) in patients with BCLC B HCC.

Conditions

Hepatocellular Carcinoma; BCLC Stage B Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Grade 3 or Higher Treatment Related Adverse Events

  Safety and tolerability will be assessed by the rate of grade 3 or higher Adverse Events (AEs), graded using the CTCAE version 5. The rate will be assessed using the Bayesian Predictive Probability approach. Due to early termination of the study, reported here is the number of participants that experienced any grade 3 or higher event.

  up to 18 months

Secondary Outcomes (5)

• Response Rate in Solid Tumors

  up to 18 months

• Response Rate in Hepatocellular Carcinoma

  up to 18 months

• Time to Progression

  up to 18 months

• Time to TACE Progression (TTTP)

  up to 18 months

• Time to Untaceable Progression

  up to 18 months

Study Arms (1)

Atezolizumab and Bevacizumab in combination with TACE

EXPERIMENTAL

THIS IS A SINGLE ARM PILOT/FEASABILITY STUDY. THE STUDY CONSISTS OF A SCREENING PERIOD (DAY -28 TO DAY -1), A TREATMENT PERIOD, AND A TREATMENT DISCONTINUATION VISIT. The atezolizumab and bevacizumab combination will be given every 21 days, atezolizumab 1200 mg and bevacizumab 15 mg/kg will be administered intravenously on a Q3 week schedule. Subjects will start the combination of bevacizumab and atezolizumab followed by TACE treatment 4 weeks ±1 week or up to 5 weeks after study drugs. Full recovery from the procedure is required prior to systemic treatment.

Drug: Atezolizumab Injection; Drug: Bevacizumab; Combination Product: Transarterial chemoembolization

Interventions

Atezolizumab Injection DRUG

Atezolizumab is a monoclonal antibody medication used to treat urothelial carcinoma, non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), small cell lung cancer (SCLC), hepatocellular carcinoma, and alveolar soft part sarcoma It is a fully humanized, engineered monoclonal antibody of Immunoglobulin G1 (IgG1) isotype against the protein programmed cell death-ligand 1 (PD-L1).

Also known as: Tecentriq

Atezolizumab and Bevacizumab in combination with TACE

Bevacizumab DRUG

Bevacizumab, is a medication used to treat a number of types of cancers and a specific eye disease. For cancer, it is given by slow injection into a vein (intravenous) and used for colon cancer, lung cancer, glioblastoma, and renal-cell carcinoma. In many of these diseases it is used as a first-line therapy. For age-related macular degeneration it is given by injection into the eye (intravitreal).

Also known as: Avastin

Atezolizumab and Bevacizumab in combination with TACE

Transarterial chemoembolization COMBINATION_PRODUCT

Transarterial chemoembolization (TACE) is a local therapy for HCC which induces tumor necrosis.

Also known as: TACE

Atezolizumab and Bevacizumab in combination with TACE

Eligibility Criteria

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

You may qualify if:

• At least 18 years old
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 within 28 days prior to registration
• No cirrhosis or Child-Pugh A cirrhosis
• Diagnosis of HCC either by imaging or biopsy
• Evidence of HCC that meets BCLC B criteria
• Patients must have adequate hepatic, bone marrow, and renal function. All screening labs should be performed within 14 days of treatment initiation.
• Patients must be candidates for TACE treatment that can be treated in up to 4 sessions
• Patients who are positive for Hepatitis B (HBc), regardless of HBs status, and have an undetectable Hepatitis B virus (HBV) viral load do not require HBV antiviral prophylaxis
• Patients who are not on HBV therapy, but positive for Hepatitis B surface antigen (HBsAg) and have an undetectable viral load are eligible for the study as long as they begin anti-viral prophylaxis prior to the start of study treatment
• Patients can have untreated hepatitis C
• At least one unidimensional tumor measurable by RECIST v1.1 criteria
• Hg ≥ 9 g/dL
• Creatinine less than 1.5 x ULN
• Serum bilirubin \< 2.5 mg/dl
• Aspartate Transferase (AST) \< 5X upper limit of normal (ULN)

You may not qualify if:

• Patients must not have signs of liver failure or history of liver failure e.g. - encephalopathy or variceal bleeding
• Uncontrolled hepatitis B infection with viral load \>500 IU/ml
• History of hypertensive crisis or hypertensive encephalopathy
• Patients who are candidates for curative intent therapy (transplant, resection, or thermal ablation) or liver transplant
• Patients who are on the transplant list
• Ascites requiring therapeutic paracentesis in the last 12 months
• Episode of hepatic encephalopathy in the last 12 months
• Extrahepatic spread: borderline portal lymph nodes deemed to be of indeterminate nature and measuring less than 2 cm are allowed
• Prior local or systemic therapy for HCC or prior TACE, excluding prior use of Radiofrequency Ablation (RFA)
• Patients cannot have known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
• Occlusion of the hepatic artery or main portal vein
• Pregnant or lactating, or intending to become pregnant during the study
• Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or other recombinant human antibodies
• Known history of Human Immunodeficiency virus (HIV) infection. No HIV testing is required.
• 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 (see Appendix 8 for a more comprehensive list of autoimmune diseases and immune deficiencies), with the following exceptions:

Sponsors & Collaborators

• Yale University: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Yale New Haven Hospital

New Haven, Connecticut, 06520, United States

Location

Related Publications (7)

• Adashek ML, Feldman M. Cytokine Release Syndrome Resulting From Anti-Programmed Death-1 Antibody: Raising Awareness Among Community Oncologists. J Oncol Pract. 2019 Sep;15(9):502-504. doi: 10.1200/JOP.19.00160. Epub 2019 Jul 16. No abstract available.

  PMID: 31310573 BACKGROUND

• Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, Maus MV, Park JH, Mead E, Pavletic S, Go WY, Eldjerou L, Gardner RA, Frey N, Curran KJ, Peggs K, Pasquini M, DiPersio JF, van den Brink MRM, Komanduri KV, Grupp SA, Neelapu SS. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant. 2019 Apr;25(4):625-638. doi: 10.1016/j.bbmt.2018.12.758. Epub 2018 Dec 25.

  PMID: 30592986 BACKGROUND

• Ravelli A, Minoia F, Davi S, Horne A, Bovis F, Pistorio A, Arico M, Avcin T, Behrens EM, De Benedetti F, Filipovic L, Grom AA, Henter JI, Ilowite NT, Jordan MB, Khubchandani R, Kitoh T, Lehmberg K, Lovell DJ, Miettunen P, Nichols KE, Ozen S, Pachlopnik Schmid J, Ramanan AV, Russo R, Schneider R, Sterba G, Uziel Y, Wallace C, Wouters C, Wulffraat N, Demirkaya E, Brunner HI, Martini A, Ruperto N, Cron RQ; Paediatric Rheumatology International Trials Organisation; Childhood Arthritis and Rheumatology Research Alliance; Pediatric Rheumatology Collaborative Study Group; Histiocyte Society. 2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis: A European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation Collaborative Initiative. Arthritis Rheumatol. 2016 Mar;68(3):566-76. doi: 10.1002/art.39332. Epub 2016 Feb 9.

  PMID: 26314788 BACKGROUND

• Riegler LL, Jones GP, Lee DW. Current approaches in the grading and management of cytokine release syndrome after chimeric antigen receptor T-cell therapy. Ther Clin Risk Manag. 2019 Feb 28;15:323-335. doi: 10.2147/TCRM.S150524. eCollection 2019.

  PMID: 30880998 BACKGROUND

• Rotz SJ, Leino D, Szabo S, Mangino JL, Turpin BK, Pressey JG. Severe cytokine release syndrome in a patient receiving PD-1-directed therapy. Pediatr Blood Cancer. 2017 Dec;64(12). doi: 10.1002/pbc.26642. Epub 2017 May 24.

  PMID: 28544595 BACKGROUND

• Schram AM, Berliner N. How I treat hemophagocytic lymphohistiocytosis in the adult patient. Blood. 2015 May 7;125(19):2908-14. doi: 10.1182/blood-2015-01-551622. Epub 2015 Mar 10.

  PMID: 25758828 BACKGROUND

• Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010 Feb;30(1):52-60. doi: 10.1055/s-0030-1247132. Epub 2010 Feb 19.

  PMID: 20175033 BACKGROUND

Related Links

• Clinical features and diagnosis of hemophagocytic lymphohistiocytosis

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

atezolizumab; Bevacizumab

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

Results Point of Contact

• Title: Wei Cheng
• Organization: Yale University

w.cheng@yale.edu

203-737-7005

Study Officials

• Stacy Stein, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Model Details: This is an open-label, single-arm study which will be performed to examine the safety and tolerability of the combination of atezolizumab and bevacizumab with TACE for patients with BCLC B HCC.

Study Record Dates

• First Submitted: March 3, 2023
• First Posted: March 20, 2023
• Study Start: June 7, 2023
• Primary Completion: December 5, 2024
• Study Completion: December 5, 2024
• Last Updated: January 15, 2025
• Results First Posted: January 15, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)