Ignite Creation Date:
2024-05-06 @ 2:15 PM
Last Modification Date:
2024-10-26 @ 1:28 PM
Study NCT ID:
NCT04265872
Status:
RECRUITING
Last Update Posted:
2023-11-30
First Post:
2020-01-23
Brief Title:
Bortezomib Followed by Pembrolizumab and Cisplatin in metTNBC
Sponsor:
Baylor Research Institute
Organization:
Baylor Research Institute
Study Overview
Official Title:
Pilot Clinical Trial of Treatment With Bortezomib to Inhibit Homologous Recombination HR Followed by Pembrolizumab and Cisplatin in Patients With Chemotherapy-Pretreated Metastatic Triple Negative Breast Cancer
Status:
RECRUITING
Status Verified Date:
2023-11
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 hypothesis of this pilot trial is that administration of bortezomib will inhibit NHEJ in metastatic TNBC leading at the time of disease progression to metastases that are HR-deficient and sensitive to pembrolizumab and cisplatin therapy The trial will include in depth analysis of the patients TNBC genome and phosphoproteome to evaluate HR-proficiency and deficiency and nuclear proteins that drive NHEJ before and upon progression with bortezomib therapy
Detailed Description:
Seventy to 80 of breast cancers have a basal gene expression profile which is characterized by homologous recombination deficiency HRD and high proliferation HRD leads to upregulation of the activity of the non-homologous end joining NHEJ error-prone pathway that repairs DNA double strand breaks a process required for TNBC survival The hypothesis of this pilot trial is that administration of bortezomib will inhibit NHEJ in metastatic TNBC leading at the time of disease progression to metastases that are HR-deficient and sensitive to pembrolizumab and cisplatin therapy A patient with an exceptional complete and durable response of her primary-refractory metastatic TNBC with PI3K pathway inhibition followed at disease progression by nab paclitaxelcisplatin provides the clinical rationale for the present trial which will utilize bortezomib to inhibit HR proficiency prior to administration of pembrolizumab and cisplatin in pretreated metastatic TNBC patients
Patients will receive bortezomib until PD followed by pembrolizumab and cisplatin until PD or a maximum of 6 cycles on study If patients are responding they may continue pembrolizumab at the physicians discretion off study Metastatic TNBC patients will undergo core needle biopsies of a metastatic lesion at study entry and at disease progression from bortezomib for NGS RPPA and other molecular analyses
Patients whose disease does not respond to pembrolizumab and cisplatin may be treated with standard of care breast cancer therapies off study at the recommendation of the treating physician
Patients will receive bortezomib until PD followed by pembrolizumab and cisplatin until PD or a maximum of 6 cycles on study If patients are responding they may continue pembrolizumab at the physicians discretion off study Metastatic TNBC patients will undergo core needle biopsies of a metastatic lesion at study entry and at disease progression from bortezomib for NGS RPPA and other molecular analyses
Patients whose disease does not respond to pembrolizumab and cisplatin may be treated with standard of care breast cancer therapies off study at the recommendation of the treating physician
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?:
False
Is an FDA AA801 Violation?:
None