Ignite Creation Date:
2024-05-06 @ 5:34 PM
Last Modification Date:
2024-10-26 @ 2:31 PM
Study NCT ID:
NCT05358639
Status:
RECRUITING
Last Update Posted:
2023-07-07
First Post:
2022-03-22
Brief Title:
Combination of Olaparib and Navitoclax in Women With HGSC and TNBC
Sponsor:
Sunnybrook Health Sciences Centre
Organization:
Sunnybrook Health Sciences Centre
Study Overview
Official Title:
A Phase I Trial of the Combination of Olaparib and Navitoclax in Women With High Grade Serous Epithelial Ovarian Cancer and Triple Negative Breast Cancer
Status:
RECRUITING
Status Verified Date:
2023-07
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:
The purpose of this Phase I study is to determine if the PARP inhibitor olaparib can be safely combined with navitoclax an inhibitor of Bcl-2Bcl-XL in women with TNBC who have somatic or germline mutations in breast cancer gene one BRCA1 and breast cancer gene two BRCA2 BRCA12 or PALB2 and in women with recurrent HGSC who have progressed greater than 6 months since their last platinum containing chemotherapy The trial is designed as an open- label multi-center Phase I interventional and translational study It will identify the dose-limiting toxicities DLTs maximum tolerated dose MTD and RP2D of olaparib combined with navitoclax for study in Phase II There is a plan for a follow on Phase II study depending on the results obtained during this Phase I trialThe rationale for this study is that for a subset of patients olaparib will increase tumor cell survival dependence on inhibition of cell death by Bcl 2Bcl- XL Thus navitoclax will augment apoptosis induced by PARP inhibition with olaparib
Detailed Description:
In this trial olaparib will be delivered alone for 14 days with the hypothesis that priming of the apoptotic machinery will be required prior to introduction of the senolytic agent navitoclax To date navitoclax and olaparib have not been combined in the clinic The Phase I study will therefore be conducted to define the recommended Phase II dose RP2D A plan for a future Phase II study will depend on the results obtained during this Phase I trial Based on the potential for overlapping toxicity particularly hematologic toxicity an interrupted dosing schedule will be used for the navitoclax Based on preclinical studies it is believed that intermittent delivery of the senolytic agent is in line with the proposed mechanism of action Subsequently the dose of navitoclax will be escalated with a fixed dose of olaparib in 28-day cycles
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None