Ignite Creation Date:
2024-05-06 @ 9:40 AM
Last Modification Date:
2024-10-26 @ 12:18 PM
Study NCT ID:
NCT03046862
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-04-19
First Post:
2017-02-06
Brief Title:
DurvalumabMEDI4736Tremelimumab in Combination With GemcitabineCisplatin in Chemotherapy-naïve Biliary Tract Cancer
Sponsor:
Seoul National University Hospital
Organization:
Seoul National University Hospital
Study Overview
Official Title:
Biomarker-oriented Study of DurvalumabMEDI4736Tremelimumab in Combination With GemcitabineCisplatin in Chemotherapy-naïve Biliary Tract Cancer
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-04
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:
Research Hypothesis The dynamics of immune systems by cytotoxic chemotherapy and its changes by combination with immuno-oncology agents will be uncovered
The combination of DurvalumabTremelimumab with gemcitabinecisplatin chemotherapy is feasible and efficacious in chemo-naïve biliary tract cancer
Purpose of the study To assess the effect of DurvalumabTremelimumab in combination with gemcitabinecisplatin on response rate RR in chemo-naïve advanced biliary tract cancer patients
The combination of DurvalumabTremelimumab with gemcitabinecisplatin chemotherapy is feasible and efficacious in chemo-naïve biliary tract cancer
Purpose of the study To assess the effect of DurvalumabTremelimumab in combination with gemcitabinecisplatin on response rate RR in chemo-naïve advanced biliary tract cancer patients
Detailed Description:
Rationale for conducting this study
1 Rational 1 The incidence of biliary tract cancer BTC is higher in Korea than the West Korea 10 new cases100000 population every year the West1-2 cases100100 population every year Therefore to conduct clinical study of BTC in Korea is very feasible and efficient
2 Rational 2 The Gemcitabinecisplatin is the current standard of care in 1st-line treatment for advanced BTC N Engl J Med 2010 362 14 1273-81 No one-targeted therapy has been approved in BTC yet The overall survival of advanced BTC with cytotoxic chemotherapy is only 8-10 months in general Therefore there is a huge unmet medical need
3 Rational 3 In recent sequencing data of BTC showed the BTC patients with the worse prognosis had significant enrichment of hypermutated tumors and a characteristic elevation in the expression of immune checkpoint molecules According immune-modulating therapies also be potentially promising options for these patients Nat Genet 2015 Sep4791003-10
4 Rational 4 In PDL1 BTC anti-PD1 Ab shows promising activity as a monotherapy Bang YJ et al ECCESMO 2015 In one clinical study of pembrolizumab 37 out of 89 BTC patients 416 showed the PDL1 tumor Among 24 PDL1 patients who were enrolled and treated with pembrolizumab 50 were Asian 625 had ECOG 1 167 had gallbladder cancer 80 were at the 3rd-line or later setting Four patients showed PR 3 from Seoul National University Hospital 4 patients SD which led the overall response rate of 174 A total 40 of patients showed tumor shrinkage The decreases in tumor size were generally maintained over time This study gives us the evidence that immune checkpoint inhibitor is working on BTC likewise other solid tumors
5 Rational 5 In recent studies have shown the combination of CTLA4 inhibitor with anti-PD1PDL1 agents shows the enhanced clinical activities especially regardless of PDL1 status This combination strategy is being actively under test in many solid tumors
6 Rational 6 Certain chemotherapeutic drugs stimulate cancer-specific immune responses by inducing immunogenic cell death and other effector mechanisms Immunity 2013 Annu Rev Immunol 2013 With the cytotoxic chemotherapy the PDL-1 is induced and this increased expression of PDL1 contributes the resistance to cytotoxic chemotherapy Successful eradication of tumors by immunogenic chemotherapy requires removal of immunosuppressive IgA PDL1plasmocytes Nature 2015 More importantly still vast majorities of dynamic changes of immune system by cytotoxic chemotherapy are unanswered
These support that the combination of cytotoxic chemotherapy with immuno-oncology agents including immune checkpoint inhibitors might be efficacious and needed
7 Rational 7 The advantages of Immunotherapy and cytotoxic chemotherapy combination are 1 can explore science on the dynamic immunologic changes by cytotoxic chemotherapy and its overcome by immunotherapy 2 easy way to be incorporated in the current clinical practice 3 can be applied to variety of tumor types such as NSCLC urothelial cancer 4 relatively affordable than immunotherapy and targeted agent combination DurvalumabTremelimumab in combination of cytotoxic chemotherapy has not been tested especially in BTC
Sample Size Determination Primary efficacy endpoint is response rate In BTC the response rate of 1st-line gemcitabinecisplatin chemotherapy is about 20 20 in BT22 clinical trial 25 in ABC-02 clinical trial Therefore we set H0 as 20 and H1 as 40 Using 75 of power and a-error of 005 a total 28 patients will be needed When we assume the drop-out rate of 10 a total of 31 patients will be enrolled
1 Rational 1 The incidence of biliary tract cancer BTC is higher in Korea than the West Korea 10 new cases100000 population every year the West1-2 cases100100 population every year Therefore to conduct clinical study of BTC in Korea is very feasible and efficient
2 Rational 2 The Gemcitabinecisplatin is the current standard of care in 1st-line treatment for advanced BTC N Engl J Med 2010 362 14 1273-81 No one-targeted therapy has been approved in BTC yet The overall survival of advanced BTC with cytotoxic chemotherapy is only 8-10 months in general Therefore there is a huge unmet medical need
3 Rational 3 In recent sequencing data of BTC showed the BTC patients with the worse prognosis had significant enrichment of hypermutated tumors and a characteristic elevation in the expression of immune checkpoint molecules According immune-modulating therapies also be potentially promising options for these patients Nat Genet 2015 Sep4791003-10
4 Rational 4 In PDL1 BTC anti-PD1 Ab shows promising activity as a monotherapy Bang YJ et al ECCESMO 2015 In one clinical study of pembrolizumab 37 out of 89 BTC patients 416 showed the PDL1 tumor Among 24 PDL1 patients who were enrolled and treated with pembrolizumab 50 were Asian 625 had ECOG 1 167 had gallbladder cancer 80 were at the 3rd-line or later setting Four patients showed PR 3 from Seoul National University Hospital 4 patients SD which led the overall response rate of 174 A total 40 of patients showed tumor shrinkage The decreases in tumor size were generally maintained over time This study gives us the evidence that immune checkpoint inhibitor is working on BTC likewise other solid tumors
5 Rational 5 In recent studies have shown the combination of CTLA4 inhibitor with anti-PD1PDL1 agents shows the enhanced clinical activities especially regardless of PDL1 status This combination strategy is being actively under test in many solid tumors
6 Rational 6 Certain chemotherapeutic drugs stimulate cancer-specific immune responses by inducing immunogenic cell death and other effector mechanisms Immunity 2013 Annu Rev Immunol 2013 With the cytotoxic chemotherapy the PDL-1 is induced and this increased expression of PDL1 contributes the resistance to cytotoxic chemotherapy Successful eradication of tumors by immunogenic chemotherapy requires removal of immunosuppressive IgA PDL1plasmocytes Nature 2015 More importantly still vast majorities of dynamic changes of immune system by cytotoxic chemotherapy are unanswered
These support that the combination of cytotoxic chemotherapy with immuno-oncology agents including immune checkpoint inhibitors might be efficacious and needed
7 Rational 7 The advantages of Immunotherapy and cytotoxic chemotherapy combination are 1 can explore science on the dynamic immunologic changes by cytotoxic chemotherapy and its overcome by immunotherapy 2 easy way to be incorporated in the current clinical practice 3 can be applied to variety of tumor types such as NSCLC urothelial cancer 4 relatively affordable than immunotherapy and targeted agent combination DurvalumabTremelimumab in combination of cytotoxic chemotherapy has not been tested especially in BTC
Sample Size Determination Primary efficacy endpoint is response rate In BTC the response rate of 1st-line gemcitabinecisplatin chemotherapy is about 20 20 in BT22 clinical trial 25 in ABC-02 clinical trial Therefore we set H0 as 20 and H1 as 40 Using 75 of power and a-error of 005 a total 28 patients will be needed When we assume the drop-out rate of 10 a total of 31 patients will be enrolled
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?:
False
Is an FDA AA801 Violation?:
None