Ignite Creation Date:
2024-05-06 @ 10:14 AM
Last Modification Date:
2024-10-26 @ 12:27 PM
Study NCT ID:
NCT03202758
Status:
COMPLETED
Last Update Posted:
2023-02-10
First Post:
2017-06-07
Brief Title:
Evaluation of the Safety and the Tolerability of Durvalumab Plus Tremelimumab Combined With FOLFOX in mCRC
Sponsor:
Centre Georges Francois Leclerc
Organization:
Centre Georges Francois Leclerc
Study Overview
Official Title:
Phase IbII Trial Evaluating the Safety Tolerability and Immunological Activity of Durvalumab MEDI4736 Anti-PD-L1 Plus Tremelimumab Anti-CTLA-4 Combined With FOLFOX in Patients With Metastatic Colorectal Cancer
Status:
COMPLETED
Status Verified Date:
2019-03
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:
MEDITREME
Brief Summary:
Colo-rectal cancer is still one of the leading causes of cancer death worldwide In France approximately 40 500 new cases are diagnosed each year With more than 17 500 deaths in France in 2011 colo-rectal cancer is responsible for more than 12 of all cancer deaths the overwhelming of deaths occurring in patients with metastatic disease
Many studies highlight the fact that colo-rectal cancer has immunogenic properties and that host immune responses can influence survival Recent data have provided a clearer understanding of the factors limiting the antitumor immune response in colo-rectal cancer One of the most critical checkpoint pathways responsible for mediating tumor-induced immune suppression is the programmed death-1 PD-1 and PD ligand 1 PD-L1 pathway
PD-1 is expressed on activated immune cells and can link to PD-L1 express on Antigen-Presenting-Cell Usually this pathway is involved in promoting T-cells tolerance and preventing tissue damage in settings of chronic inflammation In pathological context the PD-1PD-L1 pathway contributes to immune suppression and evasion Many human solid tumors including colo-rectal cancer express PD-L1 and this expression is associated with a worse prognosis The interaction of PD-1 with the ligand PD-L1 inhibits T-cell proliferation survival and effectors functions induces apoptosis of tumor-specific T cells promotes the differentiation of CD4 T cells into immunosuppressive regulatory T cells and increases the resistance of tumor cells to cytotoxic T lymphocytes attack Thus the blockage of the PD-1PD-L1 interactions represents a logical target for cancer immunotherapy and in particular colo rectal cancer immunotherapy strategy
Preclinical studies have shown that PD-L1 blockade improves the immune response by restoring T-cell effectors functions Recent work in two in vivo tumor models shows a strong interest in using an anti-PD-L1 in combination with standard treatment of colo-rectal cancer FOLFOX In these models the survival of mice that are treated with the combination therapy reached 40 when no mice were alive with FOLFOX treatment alone This result may be explained in one hand by cytotoxicity of 5FU and in the other hand by the restoration of anti-tumor immune activity of anti-PD-L1 These results suggest that the combination of chemotherapy with immunotherapy would act synergistically in patients with colo-rectal cancer
Research Hypothesis Combination of chemotherapy FOLFOX with immunotherapy association anti-PD-L1 anti-CTLA-4 would act synergistically in patients with colo-rectal cancer
Many studies highlight the fact that colo-rectal cancer has immunogenic properties and that host immune responses can influence survival Recent data have provided a clearer understanding of the factors limiting the antitumor immune response in colo-rectal cancer One of the most critical checkpoint pathways responsible for mediating tumor-induced immune suppression is the programmed death-1 PD-1 and PD ligand 1 PD-L1 pathway
PD-1 is expressed on activated immune cells and can link to PD-L1 express on Antigen-Presenting-Cell Usually this pathway is involved in promoting T-cells tolerance and preventing tissue damage in settings of chronic inflammation In pathological context the PD-1PD-L1 pathway contributes to immune suppression and evasion Many human solid tumors including colo-rectal cancer express PD-L1 and this expression is associated with a worse prognosis The interaction of PD-1 with the ligand PD-L1 inhibits T-cell proliferation survival and effectors functions induces apoptosis of tumor-specific T cells promotes the differentiation of CD4 T cells into immunosuppressive regulatory T cells and increases the resistance of tumor cells to cytotoxic T lymphocytes attack Thus the blockage of the PD-1PD-L1 interactions represents a logical target for cancer immunotherapy and in particular colo rectal cancer immunotherapy strategy
Preclinical studies have shown that PD-L1 blockade improves the immune response by restoring T-cell effectors functions Recent work in two in vivo tumor models shows a strong interest in using an anti-PD-L1 in combination with standard treatment of colo-rectal cancer FOLFOX In these models the survival of mice that are treated with the combination therapy reached 40 when no mice were alive with FOLFOX treatment alone This result may be explained in one hand by cytotoxicity of 5FU and in the other hand by the restoration of anti-tumor immune activity of anti-PD-L1 These results suggest that the combination of chemotherapy with immunotherapy would act synergistically in patients with colo-rectal cancer
Research Hypothesis Combination of chemotherapy FOLFOX with immunotherapy association anti-PD-L1 anti-CTLA-4 would act synergistically in patients with colo-rectal cancer
Detailed Description:
Phase Ib primary objective STEP 1 To determine the safety of the combination of Durvalumab Anti-PD-L1 Tremelimumab Anti-CTLA-4 FOLFOX
Phase II primary objective STEP 2 To determine the efficacy of the combination of Durvalumab Anti-PD-L1 Tremelimumab Anti-CTLA-4 FOLFOX in terms of progression free survival PFS
Phase II secondary Objective To determine efficacy of the combination of Durvalumab Anti-PD-L1 Tremelimumab Anti-CTLA-4 FOLFOX in terms of response to treatment and overall survival
Phase II primary objective STEP 2 To determine the efficacy of the combination of Durvalumab Anti-PD-L1 Tremelimumab Anti-CTLA-4 FOLFOX in terms of progression free survival PFS
Phase II secondary Objective To determine efficacy of the combination of Durvalumab Anti-PD-L1 Tremelimumab Anti-CTLA-4 FOLFOX in terms of response to treatment and overall survival
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