Evaluation of the Safety and the Tolerability of Durvalumab Plus Tremelimumab Combined With FOLFOX in mCRC (MEDITREME)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03202758|
Recruitment Status : Recruiting
First Posted : June 29, 2017
Last Update Posted : September 18, 2017
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-1/PD-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-1/PD-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.
|Condition or disease||Intervention/treatment||Phase|
|Colorectal Cancer Metastatic||Drug: Durvalumab, Tremelimumab and ,FOLFOX||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||48 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||
Step 1: Phase Ib with the aim to confirmed the safety of the association of Durvalumab (q2w 750mg) + Tremelimumab (q4w 75mg) + FOLFOX
Step 2: Phase II with the aim to assess efficacy of the association of Durvalumab (q2w 750mg) + Tremelimumab (q4w 75mg) + FOLFOX
|Masking:||None (Open Label)|
|Official Title:||Phase Ib/II 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|
|Actual Study Start Date :||August 29, 2017|
|Estimated Primary Completion Date :||August 29, 2019|
|Estimated Study Completion Date :||August 29, 2020|
Durvalumab + Tremelimumab + FOLFOX
Drug: Durvalumab, Tremelimumab and ,FOLFOX
Study will be performed in 2 step:
STEP 1 (phase Ib) will assess the safety of the combination of Durvalumab 750mg q2w + tremelimumab 75mg q4w + FOLFOX during the 2 first cycles of treatment (1 month)
STEP 2 (phase II) will assess the efficacy of the combination of Durvalumab 750mg q2w + tremelimumab 75mg q4w + FOLFOX
- Evaluation of the safety of Durvalumab plus Tremelimumab in combination with FOLFOX chemotherapy [ Time Frame: 1 month ]Criteria RECIST 1.1
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03202758
|Contact: Nicolas ISAMBERT||03 80 73 75 firstname.lastname@example.org|
|Contact: Emilie REDERSTORFF||+33 3 45 34 81 16||ERederstorff@cgfl.fr|
|CHRU Besançon||Not yet recruiting|
|Principal Investigator: Christophe Pr BORG, MD|
|Centre Georges François Leclerc||Recruiting|
|Dijon, France, 21000|
|Contact: Nicolas ISAMBERT, Pr + 33 (0)3 80 73 75 06 email@example.com|
|Contact: Emilie REDERSTORFF, PhD +33 (0)3 80 73 75 00 ext 3461 firstname.lastname@example.org|
|CHU Nantes||Not yet recruiting|
|Principal Investigator: Jaafar BENNOUNA, MD|
|Hôpital Europeen Georges Pompidou||Not yet recruiting|
|Principal Investigator: Julien TAIEB, MD|
|Hôpital Saint Antoine||Not yet recruiting|
|Principal Investigator: Thierry ANDRE, MD|