Ignite Creation Date:
2024-05-06 @ 5:29 PM
Last Modification Date:
2024-10-26 @ 2:30 PM
Study NCT ID:
NCT05327010
Status:
RECRUITING
Last Update Posted:
2024-07-03
First Post:
2022-04-13
Brief Title:
Testing the Combination of the Anti-cancer Drugs ZEN003694 ZEN-3694 and Talazoparib in Patients With Advanced Solid Tumors The ComBET Trial
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
Phase 2 Trial of the Combination of the BET Inhibitor ZEN003694 ZEN-3694 and the PARP Inhibitor Talazoparib in Patients With Molecularly-Selected Solid Tumors ComBET
Status:
RECRUITING
Status Verified Date:
2024-07
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 tests whether ZEN003694 ZEN-3694 in combination with talazoparib works to shrink tumors in patients with solid tumors that are unlikely to be cured or controlled with treatment and that may have spread from where it first started to nearby tissue lymph nodes or distant parts of the body advanced Another aim of this study is to find out if and how patients genes influence their response to this specific drug combination For this part of the study investigators will run tests using samples of patients tumor tissue and blood that will be collected during the study ZEN-3694 is an inhibitor of a family of proteins called the bromodomain and extra-terminal BET It may prevent the growth of tumor cells that overproduce BET protein Talazoparib is an inhibitor of PARP an enzyme that helps repair deoxyribonucleic acid DNA when it becomes damaged Blocking PARP may help keep cancer cells from repairing their damaged DNA causing them to die PARP inhibitors are a type of targeted therapy Genes are pieces of the DNA code that individuals inherit from their parents Some genes work to protect against cancer by correcting damage that can occur in the DNA when cells divide BRCA1 and BRCA2 are two examples of these types of genes and they are called tumor-suppressor genes For example if a person has a mutation in a BRCA12 gene they have a greatly increased risk of developing breast and ovarian cancer because their cells may no longer be able to completely repair damaged DNA It is the accumulation of DNA damage which causes a cell to change into a cancerous cell Other genes are also involved in this process and these are called DNA damage repair genes The KRAS mutation is a change in a protein in normal cells Normally KRAS serves as an information hub for signals in the cell that lead to cell growth but when there is a mutation in KRAS it signals too much and cells grow without being told to which causes cancer Combination therapy with ZEN-3694 and talazoparib may be effective at slowing or stopping tumor growth in patients with advanced cancer
Detailed Description:
PRIMARY OBJECTIVE
I To evaluate clinical response to the combination of BET bromodomain inhibitor ZEN-3694 ZEN003694 ZEN-3694 and talazoparib using objective response rate ORR complete response CR partial response PR
SECONDARY OBJECTIVES
I To confirm the safety and toxicity profile of the combination of ZEN003694 ZEN-3694 and talazoparib
II To evaluate the clinical benefit rate stable disease SD 6 months mCRPR and progression-free survival PFS
III To assess the pharmacodynamics of the combination of ZEN003694 ZEN-3694 and talazoparib using pre- and on-treatment tumor biopsies
IV To characterize pharmacodynamic changes of exploratory biomarkers to the combination of ZEN003694 ZEN-3694 and talazoparib in pre- and on-treatment tumor biopsies
V To assess putative predictive biomarkers of response and resistance to the combination of ZEN003694 ZEN-3694 and talazoparib
OUTLINE
Patients receive ZEN-3694 orally PO once daily QD and talazoparib PO QD on days 1-28 of each cycle Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity Patients undergo diagnostic imaging throughout the study and undergo blood sample collection and tumor biopsy while on study
After completion of study treatment patients are followed up 30 days after administration of the last dose of study drug and then every 3 months for up to 2 years
I To evaluate clinical response to the combination of BET bromodomain inhibitor ZEN-3694 ZEN003694 ZEN-3694 and talazoparib using objective response rate ORR complete response CR partial response PR
SECONDARY OBJECTIVES
I To confirm the safety and toxicity profile of the combination of ZEN003694 ZEN-3694 and talazoparib
II To evaluate the clinical benefit rate stable disease SD 6 months mCRPR and progression-free survival PFS
III To assess the pharmacodynamics of the combination of ZEN003694 ZEN-3694 and talazoparib using pre- and on-treatment tumor biopsies
IV To characterize pharmacodynamic changes of exploratory biomarkers to the combination of ZEN003694 ZEN-3694 and talazoparib in pre- and on-treatment tumor biopsies
V To assess putative predictive biomarkers of response and resistance to the combination of ZEN003694 ZEN-3694 and talazoparib
OUTLINE
Patients receive ZEN-3694 orally PO once daily QD and talazoparib PO QD on days 1-28 of each cycle Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity Patients undergo diagnostic imaging throughout the study and undergo blood sample collection and tumor biopsy while on study
After completion of study treatment patients are followed up 30 days after administration of the last dose of study drug and then every 3 months for up to 2 years
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 |
|---|---|---|---|
| UM1CA186688 | NIH | CTEP | httpsreporternihgovquickSearchUM1CA186688 |
| NCI-2022-02915 | REGISTRY | None | None |
| NCI10486 | None | None | None |
| 10486 | OTHER | None | None |
| 10486 | OTHER | None | None |