Ignite Creation Date:
2024-05-06 @ 8:47 AM
Last Modification Date:
2024-10-26 @ 12:05 PM
Study NCT ID:
NCT02821754
Status:
COMPLETED
Last Update Posted:
2023-03-28
First Post:
2016-06-29
Brief Title:
A Pilot Study of Combined Immune Checkpoint Inhibition in Combination With Ablative Therapies in Subjects With Hepatocellular Carcinoma HCC or Biliary Tract Carcinomas BTC
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Pilot Study of Combined Immune Checkpoint Inhibition in Combination With Ablative Therapies in Subjects With Hepatocellular Carcinoma HCC or Biliary Tract Carcinomas BTC
Status:
COMPLETED
Status Verified Date:
2023-03
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:
BACKGROUND
Various tumor ablative procedures and techniques have been shown to result in immunogenic cell death and induction of a peripheral immune response The term ablative therapies applies to trans-arterial catheter chemoembolization TACE radiofrequency ablation RFA and cryoablation CA
The underlying hypothesis of this study is that the effect of immune checkpoint inhibition can be enhanced by TACE CA and RFA in patients with advanced hepatocellular carcinoma HCC and biliary tract carcinomas BTC We have already demonstrated proof of principle as well as safety and feasibility of this approach with anti-cytotoxic T-lymphocyte-associated antigen 4 CTLA-4 therapy
Based on the concept of programmed death-ligand 1 PDL1-mediated adaptive resistance and the emerging role of programmed cell death protein 1 PD1 therapy in HCC we would like to evaluate the combination of tremelimumab and durvalumab with ablative therapies in HCC and BTC
Objectives
- To preliminarily evaluate the 6-month progression free survival PFS of combining tremelimumab and durvalumab in patients with advanced HCC either alone or with cryoablation TACE or RFA and in patients with advanced biliary tract carcinoma BTC either alone or with cryoablation or RFA
ELIGIBILITY
Histologically or cytologically confirmed diagnosis of HCC or biliary tract carcinoma OR histopathological confirmation of carcinoma in the setting of clinical and radiological characteristics which together with the pathology are highly suggestive of a diagnosis of HCC or biliary tract carcinoma
Childs-Pugh AB7 cirrhosis only is allowed If patient does not have cirrhosis this limitation does not apply
Patients must have disease that is not amenable to potentially curative resection radiofrequency ablation or liver transplantation
DESIGN
We will evaluate the combination of tremelimumab and durvalumab with ablative therapies in cohorts A HCC N40 and B BTC N30 The first N10 patients in both cohorts will receive tremelimumab and durvalumab only ie No interventional radiologic procedures
A Advanced HCC BCLC Stage BC
N 1st 10 pts No ablative procedure CryoablationRFATACE
Tremelimumab 75mg flat dose every q28 days for 4 doses Durvalumab 1500mg flat dose q28 days until end of study EOS
40 total 10 trem dur alone 10 trem dur TACE 10 trem dur RFA 10 trem dur cryo
B Intraextra-hepatic cholangiocarcinoma
N 1st 10 patients pts No ablative procedure RFA cryoablation
Tremelimumab 75mg flat dose q28 days for 4 doses Durvalumab 1500mg flat dose q28 days until EOS
30 total 10 trem dur alone 10 trem dur RFA 10 trem
BCLC Barcelona clinic liver cancer staging system
For BCLC stage B patients TACE may be repeated as per standard of care
EOS End of study treatment or meeting any of the off-treatment or off study criteria
Various tumor ablative procedures and techniques have been shown to result in immunogenic cell death and induction of a peripheral immune response The term ablative therapies applies to trans-arterial catheter chemoembolization TACE radiofrequency ablation RFA and cryoablation CA
The underlying hypothesis of this study is that the effect of immune checkpoint inhibition can be enhanced by TACE CA and RFA in patients with advanced hepatocellular carcinoma HCC and biliary tract carcinomas BTC We have already demonstrated proof of principle as well as safety and feasibility of this approach with anti-cytotoxic T-lymphocyte-associated antigen 4 CTLA-4 therapy
Based on the concept of programmed death-ligand 1 PDL1-mediated adaptive resistance and the emerging role of programmed cell death protein 1 PD1 therapy in HCC we would like to evaluate the combination of tremelimumab and durvalumab with ablative therapies in HCC and BTC
Objectives
- To preliminarily evaluate the 6-month progression free survival PFS of combining tremelimumab and durvalumab in patients with advanced HCC either alone or with cryoablation TACE or RFA and in patients with advanced biliary tract carcinoma BTC either alone or with cryoablation or RFA
ELIGIBILITY
Histologically or cytologically confirmed diagnosis of HCC or biliary tract carcinoma OR histopathological confirmation of carcinoma in the setting of clinical and radiological characteristics which together with the pathology are highly suggestive of a diagnosis of HCC or biliary tract carcinoma
Childs-Pugh AB7 cirrhosis only is allowed If patient does not have cirrhosis this limitation does not apply
Patients must have disease that is not amenable to potentially curative resection radiofrequency ablation or liver transplantation
DESIGN
We will evaluate the combination of tremelimumab and durvalumab with ablative therapies in cohorts A HCC N40 and B BTC N30 The first N10 patients in both cohorts will receive tremelimumab and durvalumab only ie No interventional radiologic procedures
A Advanced HCC BCLC Stage BC
N 1st 10 pts No ablative procedure CryoablationRFATACE
Tremelimumab 75mg flat dose every q28 days for 4 doses Durvalumab 1500mg flat dose q28 days until end of study EOS
40 total 10 trem dur alone 10 trem dur TACE 10 trem dur RFA 10 trem dur cryo
B Intraextra-hepatic cholangiocarcinoma
N 1st 10 patients pts No ablative procedure RFA cryoablation
Tremelimumab 75mg flat dose q28 days for 4 doses Durvalumab 1500mg flat dose q28 days until EOS
30 total 10 trem dur alone 10 trem dur RFA 10 trem
BCLC Barcelona clinic liver cancer staging system
For BCLC stage B patients TACE may be repeated as per standard of care
EOS End of study treatment or meeting any of the off-treatment or off study criteria
Detailed Description:
BACKGROUND
Various tumor ablative procedures and techniques have been shown to result in immunogenic cell death and induction of a peripheral immune response The term ablative therapies applies to trans-arterial catheter chemoembolization TACE radiofrequency ablation RFA and cryoablation CA
The underlying hypothesis of this study is that the effect of immune checkpoint inhibition can be enhanced by TACE CA and RFA in patients with advanced hepatocellular carcinoma HCC and biliary tract carcinomas BTC We have already demonstrated proof of principle as well as safety and feasibility of this approach with anti-CTLA4 therapy
Based on the concept of PDL1-mediated adaptive resistance and the emerging role of PD1 therapy in HCC we would like to evaluate the combination of tremelimumab and durvalumab with ablative therapies in HCC and BTC
Objectives
- To preliminarily evaluate the 6-month progression free survival PFS of combining tremelimumab and durvalumab in patients with advanced HCC either alone or with cryoablation TACE or RFA and in patients with advanced biliary tract carcinoma BTC either alone or with cryoablation or RFA
ELIGIBILITY
Histologically or cytologically confirmed diagnosis of HCC or biliary tract carcinoma OR histopathological confirmation of carcinoma in the setting of clinical and radiological characteristics which together with the pathology are highly suggestive of a diagnosis of HCC or biliary tract carcinoma
Childs-Pugh AB7 cirrhosis only is allowed If patient does not have cirrhosis this limitation does not apply
Patients must have disease that is not amenable to potentially curative resection radiofrequency ablation or liver transplantation
DESIGN
We will evaluate the combination of tremelimumab and durvalumab with ablative therapies in cohorts A1 HCC Barcelona clinic liver cancer staging system BCLC stage C N10 A2 HCC BCLC stages BC N30 and B BTC N30 The patients in cohort A1 and first 10 patients in cohort B will receive tremelimumab and durvalumab only ie no interventional radiologic procedures
Various tumor ablative procedures and techniques have been shown to result in immunogenic cell death and induction of a peripheral immune response The term ablative therapies applies to trans-arterial catheter chemoembolization TACE radiofrequency ablation RFA and cryoablation CA
The underlying hypothesis of this study is that the effect of immune checkpoint inhibition can be enhanced by TACE CA and RFA in patients with advanced hepatocellular carcinoma HCC and biliary tract carcinomas BTC We have already demonstrated proof of principle as well as safety and feasibility of this approach with anti-CTLA4 therapy
Based on the concept of PDL1-mediated adaptive resistance and the emerging role of PD1 therapy in HCC we would like to evaluate the combination of tremelimumab and durvalumab with ablative therapies in HCC and BTC
Objectives
- To preliminarily evaluate the 6-month progression free survival PFS of combining tremelimumab and durvalumab in patients with advanced HCC either alone or with cryoablation TACE or RFA and in patients with advanced biliary tract carcinoma BTC either alone or with cryoablation or RFA
ELIGIBILITY
Histologically or cytologically confirmed diagnosis of HCC or biliary tract carcinoma OR histopathological confirmation of carcinoma in the setting of clinical and radiological characteristics which together with the pathology are highly suggestive of a diagnosis of HCC or biliary tract carcinoma
Childs-Pugh AB7 cirrhosis only is allowed If patient does not have cirrhosis this limitation does not apply
Patients must have disease that is not amenable to potentially curative resection radiofrequency ablation or liver transplantation
DESIGN
We will evaluate the combination of tremelimumab and durvalumab with ablative therapies in cohorts A1 HCC Barcelona clinic liver cancer staging system BCLC stage C N10 A2 HCC BCLC stages BC N30 and B BTC N30 The patients in cohort A1 and first 10 patients in cohort B will receive tremelimumab and durvalumab only ie no interventional radiologic procedures
Study Oversight
Has Oversight DMC:
None
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?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 16-C-0135 | None | None | None |