Bortezomib Followed by Pembrolizumab and Cisplatin in metTNBC
ConditionBreast Cancer
Trial statusRecruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexFemale
Age18+
SponsorBaylor Research Institute
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Female patients ≥18 years of age
Have a diagnosis of metastatic TNBC previously treated with standard anthracycline, cyclophosphamide, and taxane chemotherapy, unless there was a contraindication to doxorubicin, in which case prior treatment with this agent is not required. NOTE: TNBC defined as ER-negative tumors with < or = 10% tumor nuclei immunoreactivity, or "ER Low Positive" as defined by the updated ASCO/CAP guidelines 2020.
Have not received more than 3 prior chemotherapy regimens for metastatic disease. Prior platinum and/or taxane therapy in the adjuvant or metastatic setting is permitted.
Have locoregional (eg, breast, chest wall, regional lymphatic) or pulmonary or hepatic metastatic disease that is amenable to core needle biopsy. If a research biopsy from a patient's metastatic disease cannot be safely obtained, a skin biopsy is permitted. If a skin biopsy cannot be safely obtained, patients may still be eligible, per physician discretion.
Disqualifiers
EXCLUSION CRITERIA
Has received a live vaccine within 30 days of the first dose of study treatment. NOTE: seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however, intranasal influenza vaccines (ie, FluMist ®) are live attenuated vaccines, and are not allowed.
Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic therapy.
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
Trial design
Design model
Single group
Treatments tested in this trial
Bortezomib; pembrolizumab and cisplatin injections--bortezomib followed by pembro/cis
Druginjection into a vein
Treatment groups
20 Participants
are divided into 1 treatment groupGroup A: Bortezomib followed by pembro/cisExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Calculate objective response rate (CR+PR) associated with bortezomib followed at disease progression with pembrolizumab and cisplatin in metastatic TNBC
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
Time frame
18 monthsSecondary outcomes
1
Calculate response
duration of response will be calculated from the time of tumor response to disease progression in patients responding to study therapy;
Time frame
18 monthsOther outcomes
1
evaluate research biopsy for homologous recombination deficiency via Next Generation Sequencing
research biopsies will be analyzed for homologous recombination deficiency via Next Generation Sequencing and Reverse Phase Protein Array
Time frame
18 monthsSponsors and contacts
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Source ClinicalTrials.gov