Improving Response to Immunotherapy in Patients With Advanced Hepatocellular Carcinoma and Chronic Hepatitis C Virus Infection With Direct-Acting Antiviral Therapy

NCT05717400 | Terminated Phase 4 Results DMC FDA Drug

• 2 other identifiers: 2022-0844NCI-2023-00828
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

To learn if giving immune checkpoint therapy (such as atezolizumab) and bevacizumab to patients who have HCC and are receiving DAAs may help to control HCC and hepatitis C.

Conditions

Liver Cancer

Outcome Measures

Primary Outcomes (2)

• Overall Response Rate

  Stable Disease in 2 out of 2 patients

  9 months

• Sustained Virologic Response (SVR)

  SVR 12 in 2 out of 2 patients

  9 months

Study Arms (1)

DAA therapy plus Bevacizumb and Atezolizumab

EXPERIMENTAL

Participants will receive bevacizumab and atezolizumab about every 3 weeks as part of the standard of care HCC treatment that is managed by your cancer doctor. In addition, Participants will continue receiving your standard of care DAAs (either sofosbuvir + velpatasvir or sofosbuvir + velpatasvir + voxilaprevir)

Drug: Bevacizumab; Drug: Atezolizumab; Drug: Sofosbuvir; Drug: Velpatasvir; Drug: Voxilaprevir; Drug: Ribavirin

Interventions

Bevacizumab DRUG

Given by vein (IV)

Also known as: Avastin™, Anti-VEGF monoclonal antibody, rhuMAb-VEGF

DAA therapy plus Bevacizumb and Atezolizumab

Atezolizumab DRUG

Given by vein (IV)

Also known as: MPDL3280A, TECENTRIQ

DAA therapy plus Bevacizumb and Atezolizumab

Sofosbuvir DRUG

Given by PO

DAA therapy plus Bevacizumb and Atezolizumab

Velpatasvir DRUG

Given by PO

DAA therapy plus Bevacizumb and Atezolizumab

Voxilaprevir DRUG

Given by PO

DAA therapy plus Bevacizumb and Atezolizumab

Ribavirin DRUG

Given by PO

DAA therapy plus Bevacizumb and Atezolizumab

Eligibility Criteria

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

You may qualify if:

• To be eligible for participation in this trial, the patient must:
• Be willing and able to provide written informed consent for the trial.
• Be at least 18 years of age on the day of signing informed consent.
• Ability to comply with the study protocol, in the investigator's judgment
• Have histologically or cytologically confirmed diagnosis of HCC (fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible) based on pathology report.
• Disease that is not amenable to curative surgical and/or locoregional therapies, or progressive disease after surgical and /or locoregional therapies
• No prior systemic therapy for HCC.
• Patients who received prior local therapy (e.g., radiofrequency ablation, percutaneous ethanol or acetic acid injection, cryoablation, high-intensity focused ultrasound, transarterial chemoembolization, transarterial embolization, etc.) are eligible provided the target lesion(s) have not been previously treated with local therapy or the target lesion(s) within the field of local therapy have subsequently progressed in accordance with RECIST version 1.1.
• ECOG Performance Status of 0 or 1
• Have a detectable HCV RNA quantitative based on the COBAS AmpliPrep/COBAS TaqMan HCV test (version 2.0, Roche Molecular Systems, Branchburg, NJ) at the time of screening.
• Have documented chronic HCV GT1 through GT6 including evidence of mixed genotype infection:
• Positive for anti-HCV antibody, HCV RNA, or any of the above HCV GTs at least 3 months before screening (HCV RNA and HCV GT must be confirmed by screening lab results) OR
• Positive for anti-HCV antibody or HCV RNA at the time of screening with a liver biopsy consistent with chronic HCV infection (or a liver biopsy performed before enrollment with evidence of chronic HCV disease, such as the presence of fibrosis) or a Fibroscan performed within 12 months of Day 1 of this study with a result of \>12.5 kPa or a FibroSure® (Fibrotest®) performed during Screening with a score of ≥0.75 or aspartate aminotransferase (AST): platelet ratio index (APRI) of \>2. APRI formula: AST ÷ lab upper limit of normal (ULN) for AST × 100 ÷ (APRI calculation to be provided by the central laboratory.)
• Have a Child-Pugh A liver score at screening or within 14 days of the first dose of the study drug.
• Have liver disease staging assessment as follows:

You may not qualify if:

• Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of trial treatment.
• Note: Patients must have recovered from all AEs due to previously therapies to ≤ Grade 1 or baseline. Subjects with ≤ Grade 2 neuropathy may be eligible Note: Subjects who have entered the follow-up phase of an investigational trial may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Note: Patients who have entered the follow-up phase of an investigational trial may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Has had esophageal or gastric variceal bleeding within the last 6 months. All subjects will be screened for esophageal varices, unless such screening has been performed in the past 12 months before first dose of treatment. If varices are present, they should be treated according to institutional standards before starting study treatment.
• Subjects with alanine aminotransferase (ALT) \>5 × ULN at Day 1 are not eligible for enrollment.
• Subjects with Total Bilirubin (Tbil) \>2.0 mg/dL at Day 1 are not eligible for enrollment
• Subjects with clinically apparent ascites or encephalopathy, or untreated varices are not eligible for enrollment. Subjects with Child-Pugh class B and C liver disease are also ineligible.
• Portal vein invasion at the main portal branch (Vp4), inferior vena cava, or cardiac involvement of HCC based on imaging.
• Has had encephalopathy in the last 6 months. Subjects on rifaximin or lactulose to control their encephalopathy are not allowed.
• Had a solid organ or hematologic transplant.
• Had prior systemic therapy for HCC other than sorafenib and/or regorafenib, or intercurrent local therapy to the liver tumor between sorafenib and/or regorafenib and study drug.
• Has evidence of history of chronic active hepatitis not caused by HCV, including but not limited to untreated active HBV (see criteria below under criterion 27), drug-induced hepatitis that is not resolved clinically, and autoimmune hepatitis.
• Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease-modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial drug.
• Has received locoregional therapy to the liver (TACE, TAE, radiation, radioembolization, or ablation) or surgery to the liver or other site within 6 weeks before the first dose of the study drug. Minor surgery must have occurred at least 7 days before the first dose of study treatment (Cycle 1, Day 1). Subjects must have recovered adequately (i.e., Grade ≤1 or baseline) from the toxicity and/or complications from any intervention before starting therapy.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Liver Neoplasms

Interventions

Bevacizumab; atezolizumab; Sofosbuvir; velpatasvir; voxilaprevir; Ribavirin

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; Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides; Ribonucleosides; Nucleosides

Results Point of Contact

• Title: Harrys A. Torres, MD
• Organization: M D Anderson Cancer Center

htorres@mdanderson.org

(713) 792-6503

Study Officials

• Harrys A. Torres, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2023
• First Posted: February 8, 2023
• Study Start: March 17, 2023
• Primary Completion: August 29, 2024
• Study Completion: August 29, 2024
• Last Updated: December 31, 2024
• Results First Posted: December 10, 2024

Record last verified: 2024-11

Locations

US (1)