Ignite Creation Date:
2024-05-06 @ 12:19 AM
Last Modification Date:
2024-10-26 @ 10:48 AM
Study NCT ID:
NCT01545141
Status:
TERMINATED
Last Update Posted:
2023-10-27
First Post:
2012-02-29
Brief Title:
Chemokine-Modulatory Regimen for Recurrent Resectable Colorectal Cancer
Sponsor:
Roswell Park Cancer Institute
Organization:
Roswell Park Cancer Institute
Study Overview
Official Title:
Randomized Phase 12 Evaluation of Neoadjuvant Administration of a Chemokine-Modulatory Regimen in Patients With Recurrent Resectable Colorectal Cancer
Status:
TERMINATED
Status Verified Date:
2023-10
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:
Determine the safety of a combination of IFN celecoxib and rintatolimod for patients with recurrent colorectal cancer This will also test whether the above combination can help the immune system to fight the tumors The results will allow the investigators to determine the preferred combination for subsequent extended studies
Detailed Description:
A previously-demonstrated correlation between the density of CRC-infiltrating effector T cells and long-term outcomes Galon et al 2006 Pages et al 2005 has been established In preclinical ex vivo studies performed using explants of resected metastatic CRC the combination of IFNα with nonselective or COX2-selective inhibitors of prostaglandin synthesis resulted in elevated production of the effector T cell-attracting chemokines CXCL10 and CCL5 This was associated with concomitant suppression of the intratumoral expression of CCL22 a Treg-attracting chemokine Muthuswamy et al 2008 Canc Res and Muthuswamy et al submitted to Canc Res 2011 However in a subset of patients the optimal results particularly with regard to CCL5 induction required additional stimulation by a third agent poly-IC a toll-like receptor -TLR Ligand
Therefore the investigators seek to establish the safety profile of a novel chemokine regimen consisting of IFN celecoxib and poly-IC The investigators also hypothesize that the proposed neoadjuvant chemokine modulation treatment in recurrent CRC patients undergoing tumor resection may increase the density of tumor infiltrating lymphocytes TILS
In addition treatment in the neoadjuvant setting will allow a comparative analysis of the effect of chemokine modulation on the local recruitment of effector-type T cells and the de-recruitment of Treg within resected tumor tissues helping to determine the preferred chemokine-modulating regimen for subsequent extended studies Such prospective studies will focus on using combinations of chemokine modulation and cancer vaccines in patients with CRC The investigators have for example recently observed that αDC1 a new type of DC vaccine Kalinski and Okada 2010 Mailliard et al 2004 is particularly effective in inducing the effector pathway of T cells differentiation This was manifested by the induction of tumor-killing function and the induction of effector-type chemokine receptors CXCR3 and CCR5 Kalinski and Okada 2010 Watchmaker et al 2010 Combining the αDC1 vaccine to a safe tolerable and efficacious CKM regimen may hold promise for patients with poor prognostic CRC
Therefore the investigators seek to establish the safety profile of a novel chemokine regimen consisting of IFN celecoxib and poly-IC The investigators also hypothesize that the proposed neoadjuvant chemokine modulation treatment in recurrent CRC patients undergoing tumor resection may increase the density of tumor infiltrating lymphocytes TILS
In addition treatment in the neoadjuvant setting will allow a comparative analysis of the effect of chemokine modulation on the local recruitment of effector-type T cells and the de-recruitment of Treg within resected tumor tissues helping to determine the preferred chemokine-modulating regimen for subsequent extended studies Such prospective studies will focus on using combinations of chemokine modulation and cancer vaccines in patients with CRC The investigators have for example recently observed that αDC1 a new type of DC vaccine Kalinski and Okada 2010 Mailliard et al 2004 is particularly effective in inducing the effector pathway of T cells differentiation This was manifested by the induction of tumor-killing function and the induction of effector-type chemokine receptors CXCR3 and CCR5 Kalinski and Okada 2010 Watchmaker et al 2010 Combining the αDC1 vaccine to a safe tolerable and efficacious CKM regimen may hold promise for patients with poor prognostic CRC
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 10-131 | OTHER | University of Pittsburgh Cancer Institute | None |