Ignite Creation Date:
2024-05-06 @ 8:50 AM
Last Modification Date:
2024-10-26 @ 12:05 PM
Study NCT ID:
NCT02834052
Status:
COMPLETED
Last Update Posted:
2024-06-07
First Post:
2016-06-15
Brief Title:
Pembrolizumab Poly-ICLC in MRP Colon Cancer
Sponsor:
Asha Nayak
Organization:
Augusta University
Study Overview
Official Title:
A Phase III Trial of Pembrolizumab MK-3475 and Poly-ICLC in Patients With Metastatic Mismatch Repair-proficient MRP Colon Cancer
Status:
COMPLETED
Status Verified Date:
2024-06
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:
The main purpose of this study is to determine the dose of poly-ICLC that is safe and tolerable when it is combined with pembrolizumab in patients with colon cancer This study will also evaluate how the combination of pembrolizumab and poly-ICLC activates the immune system in the patients blood and inside the tumor how it affects the size and number of tumors in each patient and how effective the combination is in patients with colon cancer that is unlikely to respond to pembrolizumab alone
Detailed Description:
Mismatch repair genes normally serve to fix the small glitches that occur when DNA is copied as cells divide In 1993 researchers discovered that mutations in human mismatch repair genes play a key role in the development of certain forms of colorectal cancer individuals who are deficient in these mismatch repair genes are at high risk for colorectal cancer Accumulating evidence has shown that immunotherapy may be most effective against these cancers
Programmed cell death protein 1 also known as PD-1 functions as an immune checkpoint down-regulating the immune system by preventing the activation of T-cells which in turn reduces autoimmunity and promotes self-tolerance A new class of immunotherapy drugs that block PD-1 the PD-1 inhibitors activate the immune system to attack tumors and are therefore used with varying success to treat some types of cancer
Current clinical trials are showing that patients whose tumors are mismatch repair deficient are more likely to respond to immune-boosting anti-PD-1 drugs-such as pembrolizumab-than those with tumors proficient in mismatch repair The idea is that the greater the number of DNA glitches in a tumor cell the more abnormal proteins it will produce-and the more abnormal proteins that are generated the greater the odds that the bodys immune cells will regard the tumor cells as foreign and target them for destruction Thus far PD-1 inhibitors have shown great promise for mismatch repair deficient cancer patients but not for mismatch repair proficient MRP cancer patients
In this clinical trial the investigators hypothesize that treating MRP colon cancer patients with immunostimulating agent poly-ICLC will generate an inflammatory response increasing epitope recognition and development of tumor reactive T-cells at the tumor site However interferon alpha and gamma produced by the poly-ICLC will increase PD-L1 expression and limit new T-cell development Thus PD1 blockade will increase the effectiveness of treatment with pembrolizumab
Programmed cell death protein 1 also known as PD-1 functions as an immune checkpoint down-regulating the immune system by preventing the activation of T-cells which in turn reduces autoimmunity and promotes self-tolerance A new class of immunotherapy drugs that block PD-1 the PD-1 inhibitors activate the immune system to attack tumors and are therefore used with varying success to treat some types of cancer
Current clinical trials are showing that patients whose tumors are mismatch repair deficient are more likely to respond to immune-boosting anti-PD-1 drugs-such as pembrolizumab-than those with tumors proficient in mismatch repair The idea is that the greater the number of DNA glitches in a tumor cell the more abnormal proteins it will produce-and the more abnormal proteins that are generated the greater the odds that the bodys immune cells will regard the tumor cells as foreign and target them for destruction Thus far PD-1 inhibitors have shown great promise for mismatch repair deficient cancer patients but not for mismatch repair proficient MRP cancer patients
In this clinical trial the investigators hypothesize that treating MRP colon cancer patients with immunostimulating agent poly-ICLC will generate an inflammatory response increasing epitope recognition and development of tumor reactive T-cells at the tumor site However interferon alpha and gamma produced by the poly-ICLC will increase PD-L1 expression and limit new T-cell development Thus PD1 blockade will increase the effectiveness of treatment with pembrolizumab
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
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