Ignite Creation Date:
2024-05-06 @ 10:27 AM
Last Modification Date:
2024-10-26 @ 12:30 PM
Study NCT ID:
NCT03260712
Status:
COMPLETED
Last Update Posted:
2023-11-03
First Post:
2017-08-08
Brief Title:
Pembrolizumab in Biliary Tract Cancer
Sponsor:
European Organisation for Research and Treatment of Cancer - EORTC
Organization:
European Organisation for Research and Treatment of Cancer - EORTC
Study Overview
Official Title:
Open-label First Line Single-arm Phase II Study of CisGem Combined With Pembrolizumab in Patients With Advanced or Metastatic Biliary Tract Cancer
Status:
COMPLETED
Status Verified Date:
2023-11
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-arm multi-centre phase II study in biliary tract cancer BTC patients The main objective is to detect an increase in progression-free survival rate at 6 months according to RECIST version 11 from 60 in patients with BTC treated with standard chemotherapy CT approach to 75 when treated with CT combined with pembrolizumab
Detailed Description:
Primary endpoint PFS rate at 6 months according to RECIST 11
Secondary endpoints
Best overall response rate according to RECIST 11 and iRECIST
Response duration and stable disease duration according to RECIST 11 and iRECIST
PFS rate at 6 months according to iRECIST
PFS according to RECIST 11 and iRECIST
Overall survival OS
Toxicity of treatment Common Toxicity Criteria CTCAE 50
Safety analysis A safety analysis will be done when at least 10 patients have completed at least one cycle of the three- drug combination
Events of clinical interest for this safety analysis are the following
At least Grade 2 or higher CTCAE 50 signs of acute renal failure
Grade 3 or 4 liver dysfunction defined as elevation of liver transaminases AST and ALT and alkaline phosphatase increased bilirubin
Grade 3 or 4 gastrointestinal disorders specifically colitis diarrhea and stomatitis
Grade 3 or 4 dyspnea dry cough and pneumonia
Grade 3 or 4 sepsis
Grade 3 or 4 skin toxicity If 4 out of these 10 patients experience any of the above this will trigger an IDMC review This cut-off is based on 1 previous ABC-02 study where 57 of patients experienced a grade 3 or 4 toxicity at 12 weeks of treatment and 2 KEYNOTE 028 where 17 of patients experienced grade 3 or 4 toxicity The primary analysis of efficacy endpoints will be performed in the protocol population
PFS rate at 6 months will be estimated using Kaplan Meier estimate at the time point of interest The lower bound of the one-sided 90 confidence interval CI will be calculated by Greenwoods estimation of the standard deviation If the lower bound of the one-sided 90 CI is above 60 it will be concluded that the new treatment is effective enough to warrant further evaluation in a phase III trial Assuming exponential distributions for both PFS and for the risk of drop-out power with a total sample size of 50 patients when the primary test is performed using Kaplan Meier analyses will be around 82 for a drop-out rate of 5 at 6 months and still above 80 for a drop-out rate of 10 at 6 months The one-sided type I error will be respectively 933 and 902
PFS rate at 6 months according to iRECIST will be estimated using Kaplan Meier estimate and the one-sided 90 confidence interval CI will be calculated by Greenwoods estimation of the standard deviation
BOR rate according to RECIST 11 and iBOR rate according to iRECIST will be displayed point estimate with their exact two-sided 95 confidence intervals Response duration and stable disease duration according to RECIST 11 and iRECIST will be graphically displayed using swimmer plots and bar charts
Progression free survival according to RECIST 11 and iRECIST and overall survival curves will be estimated using the Kaplan-Meier technique The safety analyses will be performed in the Safety population The worst toxicity grade per patient over the treatment period according to the CTCAE criteria version 50 will be displayed
Secondary endpoints
Best overall response rate according to RECIST 11 and iRECIST
Response duration and stable disease duration according to RECIST 11 and iRECIST
PFS rate at 6 months according to iRECIST
PFS according to RECIST 11 and iRECIST
Overall survival OS
Toxicity of treatment Common Toxicity Criteria CTCAE 50
Safety analysis A safety analysis will be done when at least 10 patients have completed at least one cycle of the three- drug combination
Events of clinical interest for this safety analysis are the following
At least Grade 2 or higher CTCAE 50 signs of acute renal failure
Grade 3 or 4 liver dysfunction defined as elevation of liver transaminases AST and ALT and alkaline phosphatase increased bilirubin
Grade 3 or 4 gastrointestinal disorders specifically colitis diarrhea and stomatitis
Grade 3 or 4 dyspnea dry cough and pneumonia
Grade 3 or 4 sepsis
Grade 3 or 4 skin toxicity If 4 out of these 10 patients experience any of the above this will trigger an IDMC review This cut-off is based on 1 previous ABC-02 study where 57 of patients experienced a grade 3 or 4 toxicity at 12 weeks of treatment and 2 KEYNOTE 028 where 17 of patients experienced grade 3 or 4 toxicity The primary analysis of efficacy endpoints will be performed in the protocol population
PFS rate at 6 months will be estimated using Kaplan Meier estimate at the time point of interest The lower bound of the one-sided 90 confidence interval CI will be calculated by Greenwoods estimation of the standard deviation If the lower bound of the one-sided 90 CI is above 60 it will be concluded that the new treatment is effective enough to warrant further evaluation in a phase III trial Assuming exponential distributions for both PFS and for the risk of drop-out power with a total sample size of 50 patients when the primary test is performed using Kaplan Meier analyses will be around 82 for a drop-out rate of 5 at 6 months and still above 80 for a drop-out rate of 10 at 6 months The one-sided type I error will be respectively 933 and 902
PFS rate at 6 months according to iRECIST will be estimated using Kaplan Meier estimate and the one-sided 90 confidence interval CI will be calculated by Greenwoods estimation of the standard deviation
BOR rate according to RECIST 11 and iBOR rate according to iRECIST will be displayed point estimate with their exact two-sided 95 confidence intervals Response duration and stable disease duration according to RECIST 11 and iRECIST will be graphically displayed using swimmer plots and bar charts
Progression free survival according to RECIST 11 and iRECIST and overall survival curves will be estimated using the Kaplan-Meier technique The safety analyses will be performed in the Safety population The worst toxicity grade per patient over the treatment period according to the CTCAE criteria version 50 will be displayed
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?:
True
Is an FDA AA801 Violation?:
None