Ignite Creation Date:
2025-12-24 @ 9:36 PM
Ignite Modification Date:
2025-12-28 @ 10:43 PM
Study NCT ID:
NCT04721132
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-09-23
First Post:
2021-01-07
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Atezolizumab and Bevacizumab Before Surgery for the Treatment of Resectable Liver Cancer
Sponsor:
M.D. Anderson Cancer Center
Organization:
Study Overview
Official Title:
An Open-Label, Phase II, Pre-Operative Study of Atezolizumab Plus Bevacizumab for Resectable Hepatocellular Carcinoma
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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.
Detailed Description:
PRIMARY OBJECTIVES:
1. To evaluate safety and tolerability of atezolizumab plus bevacizumab combination therapy in the pre-operative setting.
2. To assess the rate of pathologic complete response.
SECONDARY OBJECTIVE:
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:
1. Evaluate the predictive value of dynamic changes in fibrosis stage. Fibrosis stage will be assessed by histology by on serial tissue samples collected at baseline and at time of surgery (at 12 weeks after treatment begins).
2. To measure baseline and longitudinal changes of immune infiltration including CD8/Treg ratio and CD68+ density.
3. To explore the association between PD-L1 (and PD-L2) expression by immunohistochemistry, RNA seq genomic profiling, and antitumor efficacy
4. To evaluate baseline and longitudinal changes of tumor-necrosis factor (TNF)-α, pSTAT3, and c- MET; immune cell density such as frequency of PD-1+4-1BB+ CD8 T cells, pro-inflammatory cytokines, and hepatic fibrosis markers (APRI, FIB-4, hyaluronic acid, FibroTest \[FibroSure\]), non- alcoholic-fatty-liver-disease (NAFLD) fibrosis score (NFS), and enhanced liver fibrosis test (ELF)\] as biomarkers of response to therapy.
5. To assess the impact of therapy on the diversity of the tumor-specific T-cell repertoire
6. To explore the correlation between immunological and molecular changes in tumor tissues and peripheral blood with TTP, time to recurrence, OS, and rate of AEs. In particular, we will evaluate the potential of pre-treatment CD8 T-cell density, PD-L1 expression, and CD68 to CD8 ratio or circulating CD68+DR-/low density to predict responsiveness to checkpoint blockade.
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.
1. To evaluate safety and tolerability of atezolizumab plus bevacizumab combination therapy in the pre-operative setting.
2. To assess the rate of pathologic complete response.
SECONDARY OBJECTIVE:
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:
1. Evaluate the predictive value of dynamic changes in fibrosis stage. Fibrosis stage will be assessed by histology by on serial tissue samples collected at baseline and at time of surgery (at 12 weeks after treatment begins).
2. To measure baseline and longitudinal changes of immune infiltration including CD8/Treg ratio and CD68+ density.
3. To explore the association between PD-L1 (and PD-L2) expression by immunohistochemistry, RNA seq genomic profiling, and antitumor efficacy
4. To evaluate baseline and longitudinal changes of tumor-necrosis factor (TNF)-α, pSTAT3, and c- MET; immune cell density such as frequency of PD-1+4-1BB+ CD8 T cells, pro-inflammatory cytokines, and hepatic fibrosis markers (APRI, FIB-4, hyaluronic acid, FibroTest \[FibroSure\]), non- alcoholic-fatty-liver-disease (NAFLD) fibrosis score (NFS), and enhanced liver fibrosis test (ELF)\] as biomarkers of response to therapy.
5. To assess the impact of therapy on the diversity of the tumor-specific T-cell repertoire
6. To explore the correlation between immunological and molecular changes in tumor tissues and peripheral blood with TTP, time to recurrence, OS, and rate of AEs. In particular, we will evaluate the potential of pre-treatment CD8 T-cell density, PD-L1 expression, and CD68 to CD8 ratio or circulating CD68+DR-/low density to predict responsiveness to checkpoint blockade.
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.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: