Ignite Creation Date:
2024-05-06 @ 1:06 PM
Last Modification Date:
2024-10-26 @ 1:09 PM
Study NCT ID:
NCT03937830
Status:
RECRUITING
Last Update Posted:
2024-07-15
First Post:
2019-05-03
Brief Title:
Combined Treatment of Durvalumab Bevacizumab Tremelimumab and Transarterial Chemoembolization TACE in Subjects With Hepatocellular Carcinoma or Biliary Tract Carcinoma
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Phase II Study of Combined Treatment of Durvalumab Bevacizumab Tremelimumab and Transarterial Chemoembolization TACE in Subjects With Hepatocellular Carcinoma HCC or Biliary Tract Carcinoma BTC
Status:
RECRUITING
Status Verified Date:
2024-09-26
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
Hepatocellular carcinoma HCC is the fifth most common cancer in the world Most people with advanced HCC survive an average of 6 to 9 months Researchers are evaluating a combination of treatment drugs to delay the progression of HCC aiming to help people with HCC live longer
Objective
To study the 6-month progression-free survival in people with advanced HCC treated with bevacizumab durvalumab and TACE
Eligibility
Adults ages 18 and older with intermediate or advanced HCC
Design
Participants will be screened with a physical exam and medical history They will have tests to evaluate their hearts as well as blood and urine A CT andor MRI scans will be done during the study If a prior tumor sample is not available participants may undergo a biopsy They may undergo an endoscopy of their esophagus and stomach
Participants will get the study drugs in 21-day cycles
Two treatment drugs will be injected into a vein every 3 weeks
Patients will have an interventional treatment procedure done by interventional radiology under sedation chemotherapy beads will be infused into artery branches in the liver Participants may have to stay in the hospital for 24 hours for observation after this procedure This interventional procedure may be done more than once during the study
Participants may need to repeat some of the screening tests throughout the study
Participants may have to stop taking some of their cancer treatment drugs during the study
Participants will continue on the study until their cancer progresses or until the side effects of the treatment drugs are not tolerable
Hepatocellular carcinoma HCC is the fifth most common cancer in the world Most people with advanced HCC survive an average of 6 to 9 months Researchers are evaluating a combination of treatment drugs to delay the progression of HCC aiming to help people with HCC live longer
Objective
To study the 6-month progression-free survival in people with advanced HCC treated with bevacizumab durvalumab and TACE
Eligibility
Adults ages 18 and older with intermediate or advanced HCC
Design
Participants will be screened with a physical exam and medical history They will have tests to evaluate their hearts as well as blood and urine A CT andor MRI scans will be done during the study If a prior tumor sample is not available participants may undergo a biopsy They may undergo an endoscopy of their esophagus and stomach
Participants will get the study drugs in 21-day cycles
Two treatment drugs will be injected into a vein every 3 weeks
Patients will have an interventional treatment procedure done by interventional radiology under sedation chemotherapy beads will be infused into artery branches in the liver Participants may have to stay in the hospital for 24 hours for observation after this procedure This interventional procedure may be done more than once during the study
Participants may need to repeat some of the screening tests throughout the study
Participants may have to stop taking some of their cancer treatment drugs during the study
Participants will continue on the study until their cancer progresses or until the side effects of the treatment drugs are not tolerable
Detailed Description:
Background
Worldwide hepatocellular carcinoma HCC is the fourth most common cause of cancer related death with a median survival of 6-9 months
Biliary tract carcinoma BTC is relatively uncommon and includes cancers of the gallbladder and intra- and extra-hepatic biliary ductal system although periampullary tumors are often considered part of this group as well
A class of agents that in the recent years has been at the epicenter of immunotherapy approaches in gastrointestinal malignancies are the monoclonal antibodies mAbs against the immune checkpoint inhibitors CTLA4 PD-1 and PD-L1
Durvalumab is a human monoclonal antibody of the immunoglobulin G1 kappa IgG1 subclass Durvalumab inhibits binding of programmed cell death ligand 1 PD-L1 to programmed cell death 1 PD-1 and CD80 Anti-PD-L1 antibodies directly target tumor cells and are expected to have less adverse events in comparison with anti-PD-1 antibodies that target effector T-cells in the tumor microenvironment
Tremelimumab is a human IgG2 mAb directed against CTLA-4 Tremelimumab blocks the inhibitory effect of CTLA-4 and therefore enhances T cell activation
Angiogenesis is defined as the formation of new blood capillaries which is a complex process that promotes vascular endothelial growth factor VEGF and other proangiogenic factor expression thus enhancing metastasis Inhibition of VEGF function by bevacizumab can lead to the inhibition of the new blood vessels formation surrounding a tumor and consequently arrest the tumor growth by depriving essential nutrients and oxygen
TACE has been shown to induce anti-tumor immunity
Early phase studies have shown that anti-VEGF treatment with bevacizumab in combination with TACE decreases neovascular formation
We have previously shown that locoregional therapies can be safely combined with immune checkpoint blockade There are also preclinical data suggesting that anti-VEGF therapy may target myeloid cells with suppressor activity
Objectives
To evaluate the 6-month progression free survival PFS in participants with advanced HCC BCLC stage B treated with bevacizumab durvalumab tremelimumab and TACE
To evaluate the 6-month PFS in participants with BTC and HCC BCLC stage C treated with bevacizumab durvalumab and tremelimumab
In participants with BTC enrolled following amendment dated 032024 the primary objective will be To determine if the PFS may be improved upon compared to data from a previous trial in the same participant population
Eligibility
Histopathological confirmation of HCC or BTC 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 BTC
Participants must have evaluable or measurable disease per RECIST 11
Participants must have disease that is not amenable to potentially curative resection radiofrequency ablation or liver transplantation
Design
This is an open label Phase II trial conducted to evaluate efficacy of durvalumab bevacizumab and tremelimumab combined treatment in participants with advanced HCC BCLC stage C or BTC and efficacy of durvalumab bevacizumab tremelimumab and TACE combined treatment in participants with advanced HCC BCLC stage B
Initially 3-18 participants with HCC BCLC Stage C or BTC will be enrolled into safety run-in of Arm 1 to determine the safety of combined treatment of durvalumab bevacizumab and tremelimumab
Once safety has been determined subsequent participants with HCC BCLC Stage C and BTC will be enrolled in Arm 1 and participants with HCC BCLC Stage B will start enrollment into Arm 2 consistent of durvalumab bevacizumab tremelimumab and multiple TACE procedures
Once Arm 1 has completed accrual in the BTC cohort Arm 3 will begin accruing participants with advanced unresectable or metastatic BTC treated with durvalumab bevacizumab and tremelimumab using a different treatment schedule
Treatment will continue until progression or unbearable toxicity
Worldwide hepatocellular carcinoma HCC is the fourth most common cause of cancer related death with a median survival of 6-9 months
Biliary tract carcinoma BTC is relatively uncommon and includes cancers of the gallbladder and intra- and extra-hepatic biliary ductal system although periampullary tumors are often considered part of this group as well
A class of agents that in the recent years has been at the epicenter of immunotherapy approaches in gastrointestinal malignancies are the monoclonal antibodies mAbs against the immune checkpoint inhibitors CTLA4 PD-1 and PD-L1
Durvalumab is a human monoclonal antibody of the immunoglobulin G1 kappa IgG1 subclass Durvalumab inhibits binding of programmed cell death ligand 1 PD-L1 to programmed cell death 1 PD-1 and CD80 Anti-PD-L1 antibodies directly target tumor cells and are expected to have less adverse events in comparison with anti-PD-1 antibodies that target effector T-cells in the tumor microenvironment
Tremelimumab is a human IgG2 mAb directed against CTLA-4 Tremelimumab blocks the inhibitory effect of CTLA-4 and therefore enhances T cell activation
Angiogenesis is defined as the formation of new blood capillaries which is a complex process that promotes vascular endothelial growth factor VEGF and other proangiogenic factor expression thus enhancing metastasis Inhibition of VEGF function by bevacizumab can lead to the inhibition of the new blood vessels formation surrounding a tumor and consequently arrest the tumor growth by depriving essential nutrients and oxygen
TACE has been shown to induce anti-tumor immunity
Early phase studies have shown that anti-VEGF treatment with bevacizumab in combination with TACE decreases neovascular formation
We have previously shown that locoregional therapies can be safely combined with immune checkpoint blockade There are also preclinical data suggesting that anti-VEGF therapy may target myeloid cells with suppressor activity
Objectives
To evaluate the 6-month progression free survival PFS in participants with advanced HCC BCLC stage B treated with bevacizumab durvalumab tremelimumab and TACE
To evaluate the 6-month PFS in participants with BTC and HCC BCLC stage C treated with bevacizumab durvalumab and tremelimumab
In participants with BTC enrolled following amendment dated 032024 the primary objective will be To determine if the PFS may be improved upon compared to data from a previous trial in the same participant population
Eligibility
Histopathological confirmation of HCC or BTC 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 BTC
Participants must have evaluable or measurable disease per RECIST 11
Participants must have disease that is not amenable to potentially curative resection radiofrequency ablation or liver transplantation
Design
This is an open label Phase II trial conducted to evaluate efficacy of durvalumab bevacizumab and tremelimumab combined treatment in participants with advanced HCC BCLC stage C or BTC and efficacy of durvalumab bevacizumab tremelimumab and TACE combined treatment in participants with advanced HCC BCLC stage B
Initially 3-18 participants with HCC BCLC Stage C or BTC will be enrolled into safety run-in of Arm 1 to determine the safety of combined treatment of durvalumab bevacizumab and tremelimumab
Once safety has been determined subsequent participants with HCC BCLC Stage C and BTC will be enrolled in Arm 1 and participants with HCC BCLC Stage B will start enrollment into Arm 2 consistent of durvalumab bevacizumab tremelimumab and multiple TACE procedures
Once Arm 1 has completed accrual in the BTC cohort Arm 3 will begin accruing participants with advanced unresectable or metastatic BTC treated with durvalumab bevacizumab and tremelimumab using a different treatment schedule
Treatment will continue until progression or unbearable toxicity
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 |
|---|---|---|---|
| 19-C-0094 | None | None | None |