Ignite Creation Date:
2024-05-06 @ 3:13 PM
Last Modification Date:
2024-10-26 @ 1:45 PM
Study NCT ID:
NCT04557956
Status:
RECRUITING
Last Update Posted:
2024-07-03
First Post:
2020-09-18
Brief Title:
Testing the Addition of the Anti-cancer Drug Tazemetostat to the Usual Treatment Dabrafenib and Trametinib for Metastatic Melanoma That Has Progressed on the Usual Treatment
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
Phase 12 Study of an EZH2 Inhibitor Tazemetostat in Combination With Dual BRAFMEK Inhibition in Patients With BRAF- Mutated Metastatic Melanoma Who Progressed on Prior BRAFMEK Inhibitor Therapy
Status:
RECRUITING
Status Verified Date:
2024-04
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 III trial investigates the best dose possible benefits andor side effects of tazemetostat in combination with dabrafenib and trametinib in treating patients with melanoma that has a specific mutation in the BRAF gene BRAFV600 and that has spread to other places in the body metastatic Tazemetostat dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth Giving tazemetostat in combination with dabrafenib and trametinib may stabilize BRAFV600 mutated melanoma
Detailed Description:
PRIMARY OBJECTIVES
I To identify a maximum tolerated dose for the EZH2 inhibitor tazemetostat hydrobromide tazemetostat when used in combination with dual BRAF inhibitor dabrafenib mesylate dabrafenib and MEK inhibitor trametinib dimethyl sulfoxide trametinib therapy in BRAFMEK inhibitor-resistant BRAFV600-mutated metastatic melanoma Phase 1 II To determine if the addition of the EZH2 inhibitor tazemetostat to BRAF and MEK inhibitor therapy improves progression-free survival over single-agent EZH2 inhibitor therapy in patients with BRAFMEK inhibitor-resistant BRAFV600-mutated melanomas harboring an EZH2 alteration Phase 2
SECONDARY OBJECTIVES
I To observe and record anti-tumor activity Phase 1 II To determine the overall response rate of single-agent EZH2 inhibitor therapy tazemetostat and triplet EZH2 inhibitor tazemetostat BRAF inhibitor dabrafenib and MEK inhibitor trametinib therapy in patients with BRAFMEK inhibitor-resistant BRAFV600-mutated melanomas harboring an EZH2 alteration Phase 2
EXPLORATORY OBJECTIVE
I To explore alterations in the gene expression profile ribonucleic acid RNA-sequencing H3K27 methylome immunohistochemistry IHC chromatin immunoprecipitation ChIP-Sequencing and open chromatin landscape assay for transposase accessible chromatin ATAC-sequencing with EZH2 inhibition in fresh clinical or patient derived xenograft PDX-derived tumor samples which may reveal underlying transcriptionalepigenetic pathways mediating response to treatment
OUTLINE This is a phase I dose-escalation trial of tazemetostat followed by a phase II trial Patients in the phase I trial receive treatment as in Arm II Patients in the phase II trial are randomized to Arm I or Arm II
ARM I Patients receive tazemetostat orally PO twice daily BID on days 1-28 of each cycle Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity Patients undergo tumor biopsy computed tomography CT scan and magnetic resonance imaging MRI throughout the study At the time of progression patients may crossover to Arm II after completion of radiation therapy
ARM II Patients receive tazemetostat PO BID dabrafenib PO BID and trametinib PO once daily QD on days 1-28 of each cycle Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity Patients undergo tumor biopsy CT scan MRI multigated acquistion scan MUGA or echocardiogram ECHO throughout the study
After completion of study treatment patients are followed up at 30 days and then annually thereafter
I To identify a maximum tolerated dose for the EZH2 inhibitor tazemetostat hydrobromide tazemetostat when used in combination with dual BRAF inhibitor dabrafenib mesylate dabrafenib and MEK inhibitor trametinib dimethyl sulfoxide trametinib therapy in BRAFMEK inhibitor-resistant BRAFV600-mutated metastatic melanoma Phase 1 II To determine if the addition of the EZH2 inhibitor tazemetostat to BRAF and MEK inhibitor therapy improves progression-free survival over single-agent EZH2 inhibitor therapy in patients with BRAFMEK inhibitor-resistant BRAFV600-mutated melanomas harboring an EZH2 alteration Phase 2
SECONDARY OBJECTIVES
I To observe and record anti-tumor activity Phase 1 II To determine the overall response rate of single-agent EZH2 inhibitor therapy tazemetostat and triplet EZH2 inhibitor tazemetostat BRAF inhibitor dabrafenib and MEK inhibitor trametinib therapy in patients with BRAFMEK inhibitor-resistant BRAFV600-mutated melanomas harboring an EZH2 alteration Phase 2
EXPLORATORY OBJECTIVE
I To explore alterations in the gene expression profile ribonucleic acid RNA-sequencing H3K27 methylome immunohistochemistry IHC chromatin immunoprecipitation ChIP-Sequencing and open chromatin landscape assay for transposase accessible chromatin ATAC-sequencing with EZH2 inhibition in fresh clinical or patient derived xenograft PDX-derived tumor samples which may reveal underlying transcriptionalepigenetic pathways mediating response to treatment
OUTLINE This is a phase I dose-escalation trial of tazemetostat followed by a phase II trial Patients in the phase I trial receive treatment as in Arm II Patients in the phase II trial are randomized to Arm I or Arm II
ARM I Patients receive tazemetostat orally PO twice daily BID on days 1-28 of each cycle Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity Patients undergo tumor biopsy computed tomography CT scan and magnetic resonance imaging MRI throughout the study At the time of progression patients may crossover to Arm II after completion of radiation therapy
ARM II Patients receive tazemetostat PO BID dabrafenib PO BID and trametinib PO once daily QD on days 1-28 of each cycle Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity Patients undergo tumor biopsy CT scan MRI multigated acquistion scan MUGA or echocardiogram ECHO throughout the study
After completion of study treatment patients are followed up at 30 days and then annually thereafter
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-2020-07044 | REGISTRY | None | None |
| 10285 | OTHER | None | None |
| 10285 | OTHER | None | None |
| UM1CA186689 | NIH | None | None |
| UM1CA186704 | NIH | CTEP | httpsreporternihgovquickSearchUM1CA186704 |