Ignite Creation Date:
2024-05-06 @ 4:48 PM
Last Modification Date:
2024-10-26 @ 2:16 PM
Study NCT ID:
NCT05097911
Status:
RECRUITING
Last Update Posted:
2021-10-28
First Post:
2021-08-31
Brief Title:
Phase I Study of RNA Oligonucleotide MTL-CEBPA Atezolizumab and Bevacizumab in Patients With Advanced Hepatocellular Carcinoma
Sponsor:
National University Hospital Singapore
Organization:
National University Hospital Singapore
Study Overview
Official Title:
A Phase 1 Study of RNA Oligonucleotide MTL-CEBPA Atezolizumab and Bevacizumab in Patients With Advanced Hepatocellular Carcinoma Without Previous Systemic Therapy
Status:
RECRUITING
Status Verified Date:
2021-02
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 is a single-center phase 1 open label dose-escalation study of MTL-CEBPA co-administered with atezolizumab and bevacizumab to assess the PK PD and potential toxicities of the drug combination in advanced HCC patients and to determine the MTD OBD or RP2D The sample size employed is a minimally modified standard 33 cohort model commonly used in Phase I oncology studies Once determined the MTDOBDRP2D will be administered to an Expansion Cohort Phase Ib of 10 additional patients with advanced HCC
Detailed Description:
Objectives and Study Endpoints
Study Objectives
1 Primary Objectives
To determine the safety and tolerability of combination treatment MTL-CEBPA atezolizumab bevacizumab and determine the maximum tolerated dose MTD or optimum biologic dose OBD dose-limiting toxicities DLTs and recommended phase 2 dose RP2D for patients with advanced HCC
To determine the anti-tumor response using RECIST v11 of combination treatment MTL-CEBPA atezolizumab bevacizumab
2 Secondary Objectives
To assess the pharmacodynamics PD of combination treatment MTL-CEBPA atezolizumab bevacizumab notably on the effects on TIME tumor immune microenvironment
To assess the pharmacokinetics PK of combination treatment MTL-CEBPA atezolizumab bevacizumab
To evaluate anti-tumour response using HCC modified RECIST HCC mRECIST and immune-modified RECIST imRECIST for combination treatment MTL-CEBPA atezolizumab bevacizumab in patients with advanced HCC
Study Endpoints
1 Primary Endpoint
Dose escalation part of the study Phase 1a the primary endpoint will be dose limiting toxicity DLT as defined in Section 442
Dose expansion part of the study Phase 1b the primary endpoint will be objective response rate ORR using RECIST v11 for a response duration of at least 6 weeks
2 Secondary Endpoints
In phase 1a and 1b the secondary endpoints are
The frequency of adverse events graded according to toxicity criteria CTCAE v50 and categorized by body system and diagnosis
PK parameters defined by the maximum plasma concentration Cmax time to maximum plasma concentration Tmax area under the plasma concentration curve AUC and the half-life of MTL-CEBPA after intravenous administration
Evaluation of changes in surrogate biomarkers notably changes in levels of MDSCs
In phase 1b additional secondary endpoints include
Progression free survival PFS defined as time from first dose of study drug to until progression or relapse or death from any cause whichever occurred first
Overall survival OS defined as time from first dose of study drug until death from any cause
3 Exploratory Endpoints
In phase 1a and 1b exploratory endpoints are
Objective response rate ORR using HCC mRECIST and imRECIST
Changes from baseline of protein expression levels in blood and tumour tissue including CEBPα and P21 as well as mRNA expression levels in blood including CEBPA mRNA will be evaluated
Changes in Tumour Mutational Burden TMB and PD-L1 status biopsy samples will both be assessed
Study Objectives
1 Primary Objectives
To determine the safety and tolerability of combination treatment MTL-CEBPA atezolizumab bevacizumab and determine the maximum tolerated dose MTD or optimum biologic dose OBD dose-limiting toxicities DLTs and recommended phase 2 dose RP2D for patients with advanced HCC
To determine the anti-tumor response using RECIST v11 of combination treatment MTL-CEBPA atezolizumab bevacizumab
2 Secondary Objectives
To assess the pharmacodynamics PD of combination treatment MTL-CEBPA atezolizumab bevacizumab notably on the effects on TIME tumor immune microenvironment
To assess the pharmacokinetics PK of combination treatment MTL-CEBPA atezolizumab bevacizumab
To evaluate anti-tumour response using HCC modified RECIST HCC mRECIST and immune-modified RECIST imRECIST for combination treatment MTL-CEBPA atezolizumab bevacizumab in patients with advanced HCC
Study Endpoints
1 Primary Endpoint
Dose escalation part of the study Phase 1a the primary endpoint will be dose limiting toxicity DLT as defined in Section 442
Dose expansion part of the study Phase 1b the primary endpoint will be objective response rate ORR using RECIST v11 for a response duration of at least 6 weeks
2 Secondary Endpoints
In phase 1a and 1b the secondary endpoints are
The frequency of adverse events graded according to toxicity criteria CTCAE v50 and categorized by body system and diagnosis
PK parameters defined by the maximum plasma concentration Cmax time to maximum plasma concentration Tmax area under the plasma concentration curve AUC and the half-life of MTL-CEBPA after intravenous administration
Evaluation of changes in surrogate biomarkers notably changes in levels of MDSCs
In phase 1b additional secondary endpoints include
Progression free survival PFS defined as time from first dose of study drug to until progression or relapse or death from any cause whichever occurred first
Overall survival OS defined as time from first dose of study drug until death from any cause
3 Exploratory Endpoints
In phase 1a and 1b exploratory endpoints are
Objective response rate ORR using HCC mRECIST and imRECIST
Changes from baseline of protein expression levels in blood and tumour tissue including CEBPα and P21 as well as mRNA expression levels in blood including CEBPA mRNA will be evaluated
Changes in Tumour Mutational Burden TMB and PD-L1 status biopsy samples will both be assessed
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
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?:
None