Ignite Creation Date:
2024-05-06 @ 3:12 PM
Last Modification Date:
2024-10-26 @ 1:44 PM
Study NCT ID:
NCT04550624
Status:
RECRUITING
Last Update Posted:
2024-01-19
First Post:
2020-08-31
Brief Title:
Pembrolizumab in Combination With Lenvatinib in Patients With Advanced Biliary Tract Carcinoma
Sponsor:
Shanghai Jiahui International Hospital
Organization:
Shanghai Jiahui International Hospital
Study Overview
Official Title:
A Single Arm Phase II Study of Pembrolizumab in Combination With Lenvatinib in Patients With Advanced Biliary Tract Carcinoma After Progression on Standard Systemic Therapy
Status:
RECRUITING
Status Verified Date:
2024-01
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:
The prognosis for unresectable and metastatic biliary tract cancers BTCs including cholangiocarcinoma is poor with first line gemcitabine and cisplatin offering a median overall survival of 117 months There is no standard second- or third-line therapy for advanced BTC and this represents an unmet medical need for novel therapies The immune system plays a critical role in the development of Advanced Biliary Tract Carcinoma BTC and chronic inflammation is a common underlying risk factor for BTC Vascular endothelial growth factor VEGF signaling in BTC may lead to an immune suppression via inadequate tumor antigen presentation and an impaired T cell-mediated immune response directed against tumor antigens Lenvatinib significantly decreased the population of immunosuppressive tumor-associated macrophages and increased interferon-γ-producing cluster of differentiation 8 CD8 T cells Addition of programmed cell death protein 1 PD-1programmed death-ligand PD-L1 inhibitors helps reverse VEGF-mediated immune suppression restore T cell function and promote T cell tumor infiltration The combination of lenvatinib and pembrolizumab has demonstrated promising activity with manageable adverse events in various solid tumor types
The investigators will assess the efficacy and safety of the combination of pembrolizumab and lenvatinib in patients with advanced BTC who failed standard therapy in this phase II study
The investigators will assess the efficacy and safety of the combination of pembrolizumab and lenvatinib in patients with advanced BTC who failed standard therapy in this phase II study
Detailed Description:
Title A Single Arm Phase II Study of Pembrolizumab in combination with Lenvatinib in Patients with Advanced Biliary Tract Carcinoma after Progression on Standard Systemic Therapy Study Description The prognosis for unresectable and metastatic biliary tract cancers BTCs including cholangiocarcinoma is poor with first line gemcitabine and cisplatin offering a median overall survival of 117 months There is no standard second- or third-line therapy for advanced BTC and this represents an unmet medical need for novel therapies The immune system plays a critical role in the development of Advanced Biliary Tract Carcinoma BTC and chronic inflammation is a common underlying risk factor for BTC VEGF signaling in BTC may lead to an immune suppression via inadequate tumor antigen presentation and an impaired T cell-mediated immune response directed against tumor antigens Lenvatinib significantly decreased the population of immunosuppressive tumor-associated macrophages and increased interferon-γ-producing CD8 T cells Addition of PD-1PD-L1 inhibitors helps reverse VEGF-mediated immune suppression restore T cell function and promote T cell tumor infiltration The combination of lenvatinib and pembrolizumab has demonstrated promising activity with manageable adverse events in various solid tumor types
The investigators will assess the efficacy and safety of the combination of pembrolizumab and lenvatinib in patients with advanced BTC who failed standard therapy in this phase II study
Objectives and Endpoints
Primary Objective Evaluate the objective response rate ORR RECIST11 of lenvatinib in combination with pembrolizumab in patients with advanced BTC after progression on standard systemic therapies Secondary Objective Evaluate the safety and tolerability of lenvatinibpembrolizumab in this population Determine the duration of response DOR progression free survival PFS and overall survival OS Determine the ORR PFS and OS of subgroups stratified by molecular signatures tumor mutation burden PD-L1 expression microsatellite instability MSI status isocitrate dehydrogenase IDH or FGFR mutationfusion status in a pre-planned post-hoc analysis Define molecular correlates of response including circulating biomarkers and tumor tissue biomarkers Study Population The study will enroll 40 patients who have unresectable or metastatic histologically-confirmed advanced BTC Both male and female patients age of 18 years or older who have failed standard systemic therapy for advanced BTC with measurable disease adequate bone marrow reserve and hepaticrenal function and ECOG performance status PS 0-1 could be eligible to participate in the study after completing the study enrollment screening tests and procedures
Phase II Description of SitesFacilities Enrolling Participants The study will be conducted at Jiahui International Cancer Center Shanghai Jiahui International Hospital in collaboration with Zhongshan Hospital
Study treatmentIntervention Each cycle is defined as 21 days treatment of Pembrolizumab in combination with Lenvatinib Treatment will be administered on an outpatient basis
Pembrolizumab 200mg IV day 1 of every 21 day-cycles Lenvatinib 20mg PO once daily for 21-day cycles Study Duration 24-36 months Participant Duration up to 24 months
The investigators will assess the efficacy and safety of the combination of pembrolizumab and lenvatinib in patients with advanced BTC who failed standard therapy in this phase II study
Objectives and Endpoints
Primary Objective Evaluate the objective response rate ORR RECIST11 of lenvatinib in combination with pembrolizumab in patients with advanced BTC after progression on standard systemic therapies Secondary Objective Evaluate the safety and tolerability of lenvatinibpembrolizumab in this population Determine the duration of response DOR progression free survival PFS and overall survival OS Determine the ORR PFS and OS of subgroups stratified by molecular signatures tumor mutation burden PD-L1 expression microsatellite instability MSI status isocitrate dehydrogenase IDH or FGFR mutationfusion status in a pre-planned post-hoc analysis Define molecular correlates of response including circulating biomarkers and tumor tissue biomarkers Study Population The study will enroll 40 patients who have unresectable or metastatic histologically-confirmed advanced BTC Both male and female patients age of 18 years or older who have failed standard systemic therapy for advanced BTC with measurable disease adequate bone marrow reserve and hepaticrenal function and ECOG performance status PS 0-1 could be eligible to participate in the study after completing the study enrollment screening tests and procedures
Phase II Description of SitesFacilities Enrolling Participants The study will be conducted at Jiahui International Cancer Center Shanghai Jiahui International Hospital in collaboration with Zhongshan Hospital
Study treatmentIntervention Each cycle is defined as 21 days treatment of Pembrolizumab in combination with Lenvatinib Treatment will be administered on an outpatient basis
Pembrolizumab 200mg IV day 1 of every 21 day-cycles Lenvatinib 20mg PO once daily for 21-day cycles Study Duration 24-36 months Participant Duration up to 24 months
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