Bortezomib Followed by Pembrolizumab and Cisplatin in metTNBC
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|ClinicalTrials.gov Identifier: NCT04265872|
Recruitment Status : Recruiting
First Posted : February 12, 2020
Last Update Posted : October 8, 2021
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer||Drug: Bortezomib; pembrolizumab and cisplatin injections--bortezomib followed by pembro/cis||Early Phase 1|
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 paclitaxel/cisplatin 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 physician's 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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Health Services Research|
|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|
|Actual Study Start Date :||October 15, 2020|
|Estimated Primary Completion Date :||October 1, 2023|
|Estimated Study Completion Date :||December 1, 2023|
Experimental: Bortezomib followed by pembro/cis
There is only one arm.
Drug: Bortezomib; pembrolizumab and cisplatin injections--bortezomib followed by pembro/cis
injection into a vein
Other Name: Keytruda, Velcade, Platinol
- Calculate objective response rate (CR+PR) associated with bortezomib followed at disease progression with pembrolizumab and cisplatin in metastatic TNBC [ Time Frame: 18 months ]objective response rate will be calculated by defining the proportion of patients who have a complete or partial response to the study therapy, as determined by the treating physician
- Calculate response [ Time Frame: 18 months ]duration of response will be calculated from the time of tumor response to disease progression in patients responding to study therapy;
- evaluate research biopsy for homologous recombination deficiency via Next Generation Sequencing [ Time Frame: 18 months ]research biopsies will be analyzed for homologous recombination deficiency via Next Generation Sequencing and Reverse Phase Protein Array
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04265872
|Contact: Heather Williams, MSfirstname.lastname@example.org|
|Contact: Esther San Romanemail@example.com|
|United States, Texas|
|Baylor University Medical Center, Baylor Charles A Sammons Cancer Center||Recruiting|
|Dallas, Texas, United States, 75246|
|Contact: Joyce O'Shaughnessy, MD|
|Principal Investigator:||Joyce O'Shaughnessy, MD||Texas Oncology|