Ignite Creation Date:
2024-05-19 @ 5:34 PM
Last Modification Date:
2024-10-26 @ 3:29 PM
Study NCT ID:
NCT06410534
Status:
RECRUITING
Last Update Posted:
2024-07-15
First Post:
2024-05-10
Brief Title:
A Phase II Study Evaluating an Organ Preservation Strategy Using Immune Checkpoint Blockade for Participants With Primary Colorectal or Gastroesophageal Cancer
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Phase II Study Evaluating an Organ Preservation Strategy Using Immune Checkpoint Blockade for Participants With Primary Colorectal or Gastroesophageal Cancer
Status:
RECRUITING
Status Verified Date:
2024-09-12
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:
Background
People with colorectal cancer CRC or gastroesophageal cancer GEC must often have major surgery to remove tumors from the esophagus stomach colon or rectum These surgeries can have adverse effects on their quality of life Researchers want to know if one or two approved drugs nivolumab with or without ipilimumab can help people with CRC or GEC delay or avoid surgery
Objective
To test 1 or 2 drugs in people with CRC or GEC
Eligibility
People aged 18 years and older with CRC or GEC People with GEC must also have changes in a particular gene
Design
Participants will visit the clinic about 15 times over the first 2 years Each visit will last 4 to 8 hours
Participants will be screened They will have a physical exam with blood and urine tests They will have imaging scans Small samples of tissue will be collected from their upper or lower digestive tract where the tumor is located
Both ipilimumab and nivolumab are administered through a tube attached to a needle inserted into a vein in the arm Some participants will receive both drugs Some will receive only nivolumab Treatment will be given once every 3 weeks for up to 8 cycles up to 24 weeks
Participants will be evaluated every 6 weeks Those who are responding well will continue with the drug treatments If their disease progresses they will go to surgery
After treatment ends participants will have follow-up visits every 6 months for up to 5 years
People with colorectal cancer CRC or gastroesophageal cancer GEC must often have major surgery to remove tumors from the esophagus stomach colon or rectum These surgeries can have adverse effects on their quality of life Researchers want to know if one or two approved drugs nivolumab with or without ipilimumab can help people with CRC or GEC delay or avoid surgery
Objective
To test 1 or 2 drugs in people with CRC or GEC
Eligibility
People aged 18 years and older with CRC or GEC People with GEC must also have changes in a particular gene
Design
Participants will visit the clinic about 15 times over the first 2 years Each visit will last 4 to 8 hours
Participants will be screened They will have a physical exam with blood and urine tests They will have imaging scans Small samples of tissue will be collected from their upper or lower digestive tract where the tumor is located
Both ipilimumab and nivolumab are administered through a tube attached to a needle inserted into a vein in the arm Some participants will receive both drugs Some will receive only nivolumab Treatment will be given once every 3 weeks for up to 8 cycles up to 24 weeks
Participants will be evaluated every 6 weeks Those who are responding well will continue with the drug treatments If their disease progresses they will go to surgery
After treatment ends participants will have follow-up visits every 6 months for up to 5 years
Detailed Description:
Background
Immune checkpoint blockade ICB using antibodies against programmed cell death protein 1 PD-1 and cytotoxic T lymphocyte associated protein 4 CTLA-4 can induce major pathologic responses MPR in approximately 23 of mismatch repair MMR proficient colorectal cancers 90 of MMR deficient colorectal cancers and 74 of MMR deficient gastroesophageal cancers
MPR after ICB defined as 90 treatment response is associated with exceptional local and distant disease-free survival DFS This has been observed in participants with advanced melanoma MMR deficient colorectal cancer and MMR deficient gastroesophageal cancer
We hypothesize that it is safe to forego surgical resection in participants who have had an MPR to ICB To test this hypothesis we designed an organ preservation strategy for participants with colorectal cancer and gastroesophageal cancer using induction ICB and close interval surveillance
Objectives
Primary objective
--Determine the rate of clinical complete response CR or near-complete response nCR after induction ICB in participants with MMR proficient colorectal cancer Cohort 1 MMR deficient colorectal cancer Cohort 2 and MMR deficient gastroesophageal cancer Cohort 3
Eligibility
Age 18 years
Biopsy-confirmed stage I-III colorectal cancer MMR proficient or MMR deficient or stage I-III gastroesophageal cancer MMR deficient only
ECOG 0-1
May not have allergies or hypersensitivities to anti-PD-1 or anti-CTLA-4 administration
No concurrent major medical illnesses
No history of grade III or IV irAEs affecting major organ systems associated with the administration of single agent anti-PD-1 anti-PD-L1 or anti-CTLA-4 antibodies
Adequate organ function
Design
This is a phase II single center study evaluating induction PD-1 blockade with or without CTLA-4 blockade in participants with primary colorectal or gastroesophageal cancer
Participants will undergo baseline complete endoscopy with biopsies scans and labs Apheresis will also be performed before treatment initiation
All participants will receive nivolumab 3 mgkg every 3 weeks for an initial 4 cycles and may be eligible for an additional 4 cycles depending on response for a total of 8 cycles
Participants in Cohort 1 MMR proficient colorectal cancers and Cohort 3 MMR deficient gastroesophageal cancers will receive low-dose ipilimumab at 1 mgkg every 6 weeks for 2 cycles and may be eligible for an additional 2 cycles depending on response for a maximum of 4 cycles
Participants will be dosed with nivolumab - ipilimumab every three weeks at the NIH Clinical Center A safety evaluation will be performed before each dose including history physical exam and laboratory tests
Radiographic and endoscopic evaluation for response will be every 6 weeks while on study 6 12 18 and 24 weeks The assessment at each timepoint will dictate further management observation continuation of therapy or surgery standard chemo chemoradiation
After a maximum of 8 cycles 24 weeks
Participants with CR or nCR will be followed on a standardized surveillance protocol consisting of physical examination cross-sectional imaging and flexible endoscopy
All other participants will be recommended to undergo surgical resection or will be referred for other standard treatments if available ie chemotherapy or radiotherapy if indicated
Immune checkpoint blockade ICB using antibodies against programmed cell death protein 1 PD-1 and cytotoxic T lymphocyte associated protein 4 CTLA-4 can induce major pathologic responses MPR in approximately 23 of mismatch repair MMR proficient colorectal cancers 90 of MMR deficient colorectal cancers and 74 of MMR deficient gastroesophageal cancers
MPR after ICB defined as 90 treatment response is associated with exceptional local and distant disease-free survival DFS This has been observed in participants with advanced melanoma MMR deficient colorectal cancer and MMR deficient gastroesophageal cancer
We hypothesize that it is safe to forego surgical resection in participants who have had an MPR to ICB To test this hypothesis we designed an organ preservation strategy for participants with colorectal cancer and gastroesophageal cancer using induction ICB and close interval surveillance
Objectives
Primary objective
--Determine the rate of clinical complete response CR or near-complete response nCR after induction ICB in participants with MMR proficient colorectal cancer Cohort 1 MMR deficient colorectal cancer Cohort 2 and MMR deficient gastroesophageal cancer Cohort 3
Eligibility
Age 18 years
Biopsy-confirmed stage I-III colorectal cancer MMR proficient or MMR deficient or stage I-III gastroesophageal cancer MMR deficient only
ECOG 0-1
May not have allergies or hypersensitivities to anti-PD-1 or anti-CTLA-4 administration
No concurrent major medical illnesses
No history of grade III or IV irAEs affecting major organ systems associated with the administration of single agent anti-PD-1 anti-PD-L1 or anti-CTLA-4 antibodies
Adequate organ function
Design
This is a phase II single center study evaluating induction PD-1 blockade with or without CTLA-4 blockade in participants with primary colorectal or gastroesophageal cancer
Participants will undergo baseline complete endoscopy with biopsies scans and labs Apheresis will also be performed before treatment initiation
All participants will receive nivolumab 3 mgkg every 3 weeks for an initial 4 cycles and may be eligible for an additional 4 cycles depending on response for a total of 8 cycles
Participants in Cohort 1 MMR proficient colorectal cancers and Cohort 3 MMR deficient gastroesophageal cancers will receive low-dose ipilimumab at 1 mgkg every 6 weeks for 2 cycles and may be eligible for an additional 2 cycles depending on response for a maximum of 4 cycles
Participants will be dosed with nivolumab - ipilimumab every three weeks at the NIH Clinical Center A safety evaluation will be performed before each dose including history physical exam and laboratory tests
Radiographic and endoscopic evaluation for response will be every 6 weeks while on study 6 12 18 and 24 weeks The assessment at each timepoint will dictate further management observation continuation of therapy or surgery standard chemo chemoradiation
After a maximum of 8 cycles 24 weeks
Participants with CR or nCR will be followed on a standardized surveillance protocol consisting of physical examination cross-sectional imaging and flexible endoscopy
All other participants will be recommended to undergo surgical resection or will be referred for other standard treatments if available ie chemotherapy or radiotherapy if indicated
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 001691-C | None | None | None |