Ignite Creation Date:
2024-05-06 @ 12:14 PM
Last Modification Date:
2024-10-26 @ 12:55 PM
Study NCT ID:
NCT03704480
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-01-05
First Post:
2018-09-28
Brief Title:
Durvalumab Tremelimumab Paclitaxel in Advanced BTC After Platinum Chemotherapy
Sponsor:
GERCOR - Multidisciplinary Oncology Cooperative Group
Organization:
GERCOR - Multidisciplinary Oncology Cooperative Group
Study Overview
Official Title:
Durvalumab Plus Tremelimumab Combination Immunotherapy With or Without Weekly Paclitaxel in Patients With Advanced Biliary Tract Carcinoma BTC After Failure of Platinum-based Chemotherapy a Randomized Non-comparative Two-arm Phase II Study
Status:
ACTIVE_NOT_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:
IMMUNO-BIL
Brief Summary:
IMMUNO-BIL is a non-comparative randomized 11 phase II study This study will assess the efficacy and safety of the combination of durvalumab plus tremelimumab with or without weekly paclitaxel in patients with advanced BTC after failure of platinum-based chemotherapy
On the 25th June 2019 the maximum DLT event number was reached 610 in the durvalumab plus tremelimumab combination with paclitaxel Arm Arm B According to the Pocock boundary described in the protocol GERCOR has updated the study to discontinue enrollment in Arm B durvalumab plus tremelimumab with paclitaxel No safety concerns were raised by the IDMC in Arm A Consequently the study will resume with Arm A durvalumab plus tremelimumab only without randomization
Discontinuation of ARM BJune 2019 Durvalumab plus tremelimumab plus paclitaxel
One cycle equals 4 weeks D1D28 Durvalumab 1500 mg by IV infusion on D1 until progression or unacceptable toxicity or withdrawal of consent
Tremelimumab 75 mg by IV infusion on D1 for the first 4 cycles Paclitaxel 80 mgm2 every week for 3 weeks D1-D8-D15 by IV infusion until progression or unacceptable toxicity or withdrawal of consent at least 6 cycles at the discretion of the investigator
December 2020 Tremelimumab dosage modification based on the results of the Study 22 study Kelley RK et al ASCO20 Virtual Scientific Program 2020 showing increased efficacy response rate and progression-free survival without safety concerns with one dose of tremelimumab 300 mg cycle 1 instead of four doses of 75 mg cycle 1 to cycle 4 in combination with durvalumab 1500 mg Q4W in hepatocellular carcinoma Following these results we have changed the tremelimumab 75 mg x 4 schedule for the 300 mg x 1 schedule The inclusion of 106 additional patients will be required to adequately evaluate the efficacy of this administration schedule
ARM A Durvalumab plus tremelimumab patients included before 31122020 One cycle equals 4 weeks D1D28
Durvalumab 1500 mg by IV infusion on D1 until progression or unacceptable toxicity or withdrawal of consent
Tremelimumab 75 mg by IV infusion on D1 for the first 4 cycles
On the 25th June 2019 the maximum DLT event number was reached 610 in the durvalumab plus tremelimumab combination with paclitaxel Arm Arm B According to the Pocock boundary described in the protocol GERCOR has updated the study to discontinue enrollment in Arm B durvalumab plus tremelimumab with paclitaxel No safety concerns were raised by the IDMC in Arm A Consequently the study will resume with Arm A durvalumab plus tremelimumab only without randomization
Discontinuation of ARM BJune 2019 Durvalumab plus tremelimumab plus paclitaxel
One cycle equals 4 weeks D1D28 Durvalumab 1500 mg by IV infusion on D1 until progression or unacceptable toxicity or withdrawal of consent
Tremelimumab 75 mg by IV infusion on D1 for the first 4 cycles Paclitaxel 80 mgm2 every week for 3 weeks D1-D8-D15 by IV infusion until progression or unacceptable toxicity or withdrawal of consent at least 6 cycles at the discretion of the investigator
December 2020 Tremelimumab dosage modification based on the results of the Study 22 study Kelley RK et al ASCO20 Virtual Scientific Program 2020 showing increased efficacy response rate and progression-free survival without safety concerns with one dose of tremelimumab 300 mg cycle 1 instead of four doses of 75 mg cycle 1 to cycle 4 in combination with durvalumab 1500 mg Q4W in hepatocellular carcinoma Following these results we have changed the tremelimumab 75 mg x 4 schedule for the 300 mg x 1 schedule The inclusion of 106 additional patients will be required to adequately evaluate the efficacy of this administration schedule
ARM A Durvalumab plus tremelimumab patients included before 31122020 One cycle equals 4 weeks D1D28
Durvalumab 1500 mg by IV infusion on D1 until progression or unacceptable toxicity or withdrawal of consent
Tremelimumab 75 mg by IV infusion on D1 for the first 4 cycles
Detailed Description:
Biliary tract carcinoma BTC adenocarcinoma in more than 90 of cases is the second primary liver tumor in incidence after hepatocellular carcinoma 2000 new casesyear in France
The prognosis of biliary malignancies is poor with a 5-year overall survival rate OS of about 10-15 most often due to late diagnosis at an advanced stage
In advanced BTC the gemcitabine plus platinum cisplatin GEMCIS or oxaliplatin GEMOX doublet of chemotherapy is the standard first-line treatment and no targeted therapy has been validated in this indication to date There is no second-line therapeutic standard chemotherapy mainly 5-FU-based combination yields limited median progression-free survival PFS and OS of abouty 2-3 months and 6-7 months respectively justifying the exploration of new therapeutic options
Immune therapies mainly immune checkpoint inhibitors ICI have opened new opportunities in cancer therapy Hence anti-CTLA-4 and anti-PD-1PD-L1 monoclonal antibodies mAb have demonstrated robust clinical activity and obtained FDA approval in several cancers Recent data showed encouraging results with anti-PD-1 mAb as a monotherapy in PD-L1-positive pre-treated advanced BTC The effects of ICI in combination with second-line chemotherapy in patients with advanced BTC have not been explored to date
Platinum salts can induce immunogenic cell death Therefore previous treatment with platinum may increase tumor immunogenicity and sensitivity to immune therapy particularly ICI The second-line setting after failure of platinum-based chemotherapy may then be an optimal biological context for testing immune therapy in advanced BTC
Durvalumab is a human immunoglobulin Ig G1 kappa IgG1κ anti-PD-L1 mAb Tremelimumab is a human IgG2 anti-CTLA-4 mAb Paclitaxel is a chemotherapy belonging to the taxane family Taxanes may enhance the effect of immunotherapy by increasing the sensitivity of the tumor and activating the immune system Taxanes are used in some patients with advanced biliary cancer
These data suggest that BTC may be a good candidate for immune therapy The combination of anti-CTL4 and anti-PD1PD-L1 mAb is expected to be active in both immune-inflamed and non-inflamed BTC and in PD-L1 high and low tumors
The prognosis of biliary malignancies is poor with a 5-year overall survival rate OS of about 10-15 most often due to late diagnosis at an advanced stage
In advanced BTC the gemcitabine plus platinum cisplatin GEMCIS or oxaliplatin GEMOX doublet of chemotherapy is the standard first-line treatment and no targeted therapy has been validated in this indication to date There is no second-line therapeutic standard chemotherapy mainly 5-FU-based combination yields limited median progression-free survival PFS and OS of abouty 2-3 months and 6-7 months respectively justifying the exploration of new therapeutic options
Immune therapies mainly immune checkpoint inhibitors ICI have opened new opportunities in cancer therapy Hence anti-CTLA-4 and anti-PD-1PD-L1 monoclonal antibodies mAb have demonstrated robust clinical activity and obtained FDA approval in several cancers Recent data showed encouraging results with anti-PD-1 mAb as a monotherapy in PD-L1-positive pre-treated advanced BTC The effects of ICI in combination with second-line chemotherapy in patients with advanced BTC have not been explored to date
Platinum salts can induce immunogenic cell death Therefore previous treatment with platinum may increase tumor immunogenicity and sensitivity to immune therapy particularly ICI The second-line setting after failure of platinum-based chemotherapy may then be an optimal biological context for testing immune therapy in advanced BTC
Durvalumab is a human immunoglobulin Ig G1 kappa IgG1κ anti-PD-L1 mAb Tremelimumab is a human IgG2 anti-CTLA-4 mAb Paclitaxel is a chemotherapy belonging to the taxane family Taxanes may enhance the effect of immunotherapy by increasing the sensitivity of the tumor and activating the immune system Taxanes are used in some patients with advanced biliary cancer
These data suggest that BTC may be a good candidate for immune therapy The combination of anti-CTL4 and anti-PD1PD-L1 mAb is expected to be active in both immune-inflamed and non-inflamed BTC and in PD-L1 high and low tumors
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?:
None
Is an FDA AA801 Violation?:
None