Ignite Creation Date:
2024-05-06 @ 7:14 PM
Last Modification Date:
2024-10-26 @ 3:03 PM
Study NCT ID:
NCT05947500
Status:
RECRUITING
Last Update Posted:
2024-07-11
First Post:
2023-07-13
Brief Title:
Testing the Combination of Two Anticancer Drugs M1774 Tuvusertib and Avelumab to Evaluate Their Safety and Effectiveness in Treating Merkel Cell Skin Cancer MATRiX Trial
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
A Randomized Phase 2 Study of ATR Inhibition in Advanced PD-L1-Refractory Merkel Cell Carcinoma The MATRiX Trial
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 tuvusertib in combination with avelumab to tuvusertib alone to determine whether the combination therapy will lengthen the time before the cancer starts getting worse in patients with Merkel cell cancer that has not responded to previous treatment refractory Tuvusertib is a drug that inhibits an enzyme called ataxia telangiectasia and Rad3 related ATR kinase which is an enzyme that plays a role in repair of damaged deoxyribonucleic acid DNA as well as tumor cell replication and survival It may lead to tumor cell death by inhibiting ATR kinase activity Immunotherapy with monoclonal antibodies such as avelumab may help the bodys immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread Giving tuvusertib in combination with avelumab may lengthen the time before Merkel cell cancer starts getting worse compared to giving avelumab alone
Detailed Description:
PRIMARY OBJECTIVE
I To compare the potential efficacy using progression free survival PFS of ATR inhibition alone to ATR inhibition plus anti-PD-L1 therapy through a randomized clinical trial for patients with advanced Merkel cell carcinoma MCC who have progressed on anti-PDL1 therapy
SECONDARY OBJECTIVES
I To compare the clinical activity of ATR inhibition alone to that in combination with avelumab through a randomized clinical trial for patients with advanced MCC that has progressed after PD-1 pathway blockade
II To identify gene expression-based immunologic replication stress neuroendocrine NE differentiation signatures predictive of response to ATR inhibition in advanced immunotherapy-refractory MCC tumors through ribonucleic acid sequencing RNAseq
EXPLORATORY OBJECTIVES
I To examine the association of various biomarkers with the clinical activity of ATR inhibition alone or in combination with PD-L1 pathway blockade
II To explore the safety and efficacy PFS overall response rate ORR and overall survival OS of the addition of avelumab to M1774 after documented progressive disease of M1774 monotherapy
OUTLINE Patients are randomized to 1 of 2 arms
ARM 1 Patients receive tuvusertib orally PO once daily QD on days 1-14 of each cycle Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity Patients also undergo computed tomography CT positron emission tomography PETCT or magnetic resonance imaging MRI biopsy and collection of blood and stoolrectal swabs at screening and on study Patients with documented progression may cross over to Arm 2
ARM 2 Patients receive tuvusertib PO QD on days 1-14 of each cycle and avelumab intravenously IV over 60 minutes on day 1 of each cycle Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity Patients also undergo CT PETCT or MRI biopsy and collection of blood and stool at screening and on study
After completion of study treatment patients are followed up at 30 days and then every 6 months for 2 years from the last dose of treatment
I To compare the potential efficacy using progression free survival PFS of ATR inhibition alone to ATR inhibition plus anti-PD-L1 therapy through a randomized clinical trial for patients with advanced Merkel cell carcinoma MCC who have progressed on anti-PDL1 therapy
SECONDARY OBJECTIVES
I To compare the clinical activity of ATR inhibition alone to that in combination with avelumab through a randomized clinical trial for patients with advanced MCC that has progressed after PD-1 pathway blockade
II To identify gene expression-based immunologic replication stress neuroendocrine NE differentiation signatures predictive of response to ATR inhibition in advanced immunotherapy-refractory MCC tumors through ribonucleic acid sequencing RNAseq
EXPLORATORY OBJECTIVES
I To examine the association of various biomarkers with the clinical activity of ATR inhibition alone or in combination with PD-L1 pathway blockade
II To explore the safety and efficacy PFS overall response rate ORR and overall survival OS of the addition of avelumab to M1774 after documented progressive disease of M1774 monotherapy
OUTLINE Patients are randomized to 1 of 2 arms
ARM 1 Patients receive tuvusertib orally PO once daily QD on days 1-14 of each cycle Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity Patients also undergo computed tomography CT positron emission tomography PETCT or magnetic resonance imaging MRI biopsy and collection of blood and stoolrectal swabs at screening and on study Patients with documented progression may cross over to Arm 2
ARM 2 Patients receive tuvusertib PO QD on days 1-14 of each cycle and avelumab intravenously IV over 60 minutes on day 1 of each cycle Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity Patients also undergo CT PETCT or MRI biopsy and collection of blood and stool at screening and on study
After completion of study treatment patients are followed up at 30 days and then every 6 months for 2 years from the last dose of treatment
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-2023-05259 | REGISTRY | None | None |
| 10592 | OTHER | None | None |
| 10592 | OTHER | None | None |
| P30CA015704 | NIH | CTEP | httpsreporternihgovquickSearchP30CA015704 |