Ignite Creation Date:
2024-05-06 @ 6:55 PM
Last Modification Date:
2024-10-26 @ 2:57 PM
Study NCT ID:
NCT05836584
Status:
RECRUITING
Last Update Posted:
2024-07-08
First Post:
2023-04-26
Brief Title:
Testing Immunotherapy Atezolizumab With or Without Chemotherapy in Locoregional MSI-HdMMR Gastric and Gastroesophageal Junction GEJ Cancer
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
A Randomized Phase II Study of Perioperative Atezolizumab - Chemotherapy in Resectable MSI-HdMMR Gastric and Gastroesophageal Junction GEJ Cancer
Status:
RECRUITING
Status Verified Date:
2024-08
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:
This phase II trial compares atezolizumab in combination with chemotherapy docetaxel oxaliplatin leucovorin calcium fluorouracil capecitabine to atezolizumab alone for controlling the growth andor spreading of the disease in patients with gastric or gastroesophageal junction JEG cancer that has not spread from where it first started local or only has spread to nearby lymph nodes or tissue locoregional and has high microsatellite instability MSI-H and mismatch repair deficiency dMMR The mismatch repair MMR system in the body corrects errors made during the copying of DNA and serves as a proofreading function If this system isnt working correctly mutations changes in DNA occur which can allow the cancer to grow or spread This is called dMMR deficient mismatch repair MSI-H describes cancer cells that have a high number of mutations within microsatellites For example microsatellite testing that shows mutations in 30 or more microsatellites is called microsatellite instability-high MSI-H Microsatellites are short repeated sequences of DNA There is evidence that MSI-H dMMR gastric or GEJ tumors respond well to immunotherapy Immunotherapy with monoclonal antibodies such as atezolizumab may help the bodys immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread Docetaxel is in a class of medications called taxanes It stops tumor cells from growing and dividing and may kill them Oxaliplatin is in a class of medications called platinum-containing antineoplastic agents It damages the cells DNA and may kill tumor cells Capecitabine is in a class of medications called antimetabolites It is taken up by tumor cells and breaks down into fluorouracil a substance that kills tumor cells Chemotherapy drugs such as leucovorin calcium and fluorouracil work in different ways to stop the growth of tumor cells either by killing the cells by stopping them from dividing or by stopping them from spreading Using atezolizumab as immunotherapy with and following chemotherapy versus atezolizumab alone prior to and after surgery may shrink or stabilize the tumor in patients with MSI-HdMMR localized gastric or GEJ cancer and may increase the length of time after treatment that cancer does not come back or get worse
Detailed Description:
PRIMARY OBJECTIVE
I To compare three-year event-free survival EFS following the administration of perioperative atezolizumab and chemotherapy versus atezolizumab alone in patients with resectable microsatellite instability-high MSI-Hmismatch repair deficiency dMMR gastric and gastroesophageal junction GEJ cancer
SECONDARY OBJECTIVES
I To assess tumor regression grade TRG rates following the administration of perioperative atezolizumab and chemotherapy versus atezolizumab in patients with resectable MSI-HdMMR gastric and gastroesophageal junction GEJ cancer
II To assess overall survival OS following the administration of perioperative atezolizumab and chemotherapy versus atezolizumab in patients with resectable MSI-HdMMR gastric and gastroesophageal junction GEJ cancer
III To assess the toxicity associated with the administration of perioperative atezolizumab and chemotherapy versus atezolizumab in patients with resectable MSI-HdMMR gastric and gastroesophageal junction GEJ cancer
IV To correlate circulating tumor-derived deoxyribonucleic acid ctDNA clearance defined as 50 reduction or a reduction to undetectable levels with TRG EFS and OS
OUTLINE Patients are randomized to 1 of 2 arms
ARM A
NEOADJUVANT THERAPY Patients receive physicians choice of chemotherapy regimen consisting of 4 cycles of docetaxel intravenously IV oxaliplatin IV leucovorin calcium IV and fluorouracil IV FLOT or 4 cycles of oxaliplatin IV leucovorin calcium IV and fluorouracil IV mFOLFOX or 3 cycles of oxaliplatin IV and capecitabine orally PO CAPOX in addition to atezolizumab IV on study
SURGERY Patients undergo surgery with lymphadenectomy on study
ADJUVANT THERAPY Patients receive FLOT mFOLFOX or CAPOX and atezolizumab IV as in Neoadjuvant Therapy and then receive atezolizumab IV alone
ARM B
NEOADJUVANT THERAPY Patients receive 3 cycles of atezolizumab IV on study
SURGERY Patients undergo surgery with lymphadenectomy on study
ADJUVANT THERAPY Patients receive 9 cycles of atezolizumab IV on study
All patients also undergo computed tomography CT or magnetic resonance imaging MRI throughout the trial Patients may optionally undergo positron emission tomography PETCT andor collection of blood samples throughout the trial Patients may also undergo echocardiography ECHO throughout the trial as clinically indicated
Patients are followed up for 10 years from the date of randomization
I To compare three-year event-free survival EFS following the administration of perioperative atezolizumab and chemotherapy versus atezolizumab alone in patients with resectable microsatellite instability-high MSI-Hmismatch repair deficiency dMMR gastric and gastroesophageal junction GEJ cancer
SECONDARY OBJECTIVES
I To assess tumor regression grade TRG rates following the administration of perioperative atezolizumab and chemotherapy versus atezolizumab in patients with resectable MSI-HdMMR gastric and gastroesophageal junction GEJ cancer
II To assess overall survival OS following the administration of perioperative atezolizumab and chemotherapy versus atezolizumab in patients with resectable MSI-HdMMR gastric and gastroesophageal junction GEJ cancer
III To assess the toxicity associated with the administration of perioperative atezolizumab and chemotherapy versus atezolizumab in patients with resectable MSI-HdMMR gastric and gastroesophageal junction GEJ cancer
IV To correlate circulating tumor-derived deoxyribonucleic acid ctDNA clearance defined as 50 reduction or a reduction to undetectable levels with TRG EFS and OS
OUTLINE Patients are randomized to 1 of 2 arms
ARM A
NEOADJUVANT THERAPY Patients receive physicians choice of chemotherapy regimen consisting of 4 cycles of docetaxel intravenously IV oxaliplatin IV leucovorin calcium IV and fluorouracil IV FLOT or 4 cycles of oxaliplatin IV leucovorin calcium IV and fluorouracil IV mFOLFOX or 3 cycles of oxaliplatin IV and capecitabine orally PO CAPOX in addition to atezolizumab IV on study
SURGERY Patients undergo surgery with lymphadenectomy on study
ADJUVANT THERAPY Patients receive FLOT mFOLFOX or CAPOX and atezolizumab IV as in Neoadjuvant Therapy and then receive atezolizumab IV alone
ARM B
NEOADJUVANT THERAPY Patients receive 3 cycles of atezolizumab IV on study
SURGERY Patients undergo surgery with lymphadenectomy on study
ADJUVANT THERAPY Patients receive 9 cycles of atezolizumab IV on study
All patients also undergo computed tomography CT or magnetic resonance imaging MRI throughout the trial Patients may optionally undergo positron emission tomography PETCT andor collection of blood samples throughout the trial Patients may also undergo echocardiography ECHO throughout the trial as clinically indicated
Patients are followed up for 10 years from the date of randomization
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 |
|---|---|---|---|
| NCI-2023-03192 | REGISTRY | None | None |
| EA2212 | OTHER | None | None |
| EA2212 | OTHER | None | None |
| U10CA180820 | NIH | CTEP | httpsreporternihgovquickSearchU10CA180820 |