Breast CancerEarly Phase 1NCT04265872
Bortezomib Followed by Pembrolizumab and Cisplatin in metTNBC
A Early Phase 1 study testing Bortezomib; pembrolizumab and cisplatin injections--bortezomib followed by pembro/cis in people with Breast Cancer, run by Baylor Research Institute at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Bortezomib; pembrolizumab and cisplatin injections--bortezomib followed by pembro/cis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Oct 2020to 31 Mar 2027
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- A patient will be eligible for inclusion in this study if she meets all of the following criteria:
- 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.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (See Appendix I)
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- Have adequate hematologic function, defined by:
- Absolute neutrophil count (ANC) >1500/μL
- Platelet count ≥100,000/μL
- Hemoglobin ≥9 g/dL or ≥5.6 mmol/L
- Have adequate liver function, defined by:
- AST and ALT ≤2.5 x the upper limit of normal (ULN) or ≤5 x ULN in presence of liver metastases
- Total bilirubin ≤1.5 x ULN OR direct bilirubin ≤ULN for patients with total bilirubin levels >1.5 × ULN
- Have adequate renal function, defined by:
- Serum creatinine ≤1.5 x ULN or calculated creatinine clearance of ≥30 mL/min
- Have adequate coagulation function, defined by:
- International Normalized Ratio (INR) OR prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤1.5 × ULN.
- If patient is receiving anticoagulant therapy, PT or aPTT must be within therapeutic range of intended use of anticoagulants.
- Patients who have a history of brain metastasis are eligible for the study provided that all the following criteria are met:
- Brain metastases which have been treated
- Off-treatment with steroids for 2 weeks before administration of the first dose of bortezomib
- No ongoing requirement for dexamethasone or anti-epileptic drugs
- No clinical or radiological evidence of progression of brain metastases
- Patient must be accessible for treatment and follow-up.
- All patients must be able to understand the investigational nature of the study and give written informed consent prior to study entry.
Who cannot join
- A patient will be ineligible for inclusion in this study if she meets any of the following 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.
- Has a known history of Human Immunodeficiency Virus (HIV)
- Has known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection
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- Has a history of non-infectious pneumonitis that required steroids or current pneumonitis
- Has peripheral neuropathy ≥grade 2
- Has completed previous radiotherapy for metastatic disease <2 weeks prior to study treatment initiation
- Has an active infection requiring systemic therapy
- Has significant cardiovascular disease, such as:
- History of myocardial infarction, acute coronary syndrome, or coronary angioplasty/stenting/bypass grafting within the last 6 months
- Congestive heart failure (CHF) New York Heart Association (NYHA) Class II-IV, or history of CHF NYHA class III or IV.
- Has a known history of active tuberculosis
- Women who are pregnant or lactating. All patients with reproductive potential must agree to use effective contraception from time of study entry until at least 3 months after the last administration of study drug.
- Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation such as:
- severe impaired lung functions as defined as spirometry and DLCO that is 50% of the normal predicted value and/or O2 saturation that is 88% or less at rest on room air
- liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C).
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the Treating Physician.
- Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to study treatment (this would not include bortezomib while on study). Monoclonal antibody agents should have a 4-week (28 day) washout period.
- Any other investigational or anti-cancer treatments while participating in this study
- Any other active malignancy
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Baylor University Medical Center, Baylor Charles A Sammons Cancer Center
Dallas, Texas, 75246
Joyce O'Shaughnessy, MD
About this study
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
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.
Read the 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 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.
- Conditions
- Breast Cancer
- Being tested
- Bortezomib; pembrolizumab and cisplatin injections--bortezomib followed by pembro/cis
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bortezomib; pembrolizumab and cisplatin injections--bortezomib followed by pembro/cisDrug
Also called Keytruda, Velcade, Platinol
injection into a vein
| Study group | Role | What they receive |
|---|---|---|
| Bortezomib followed by pembro/cis | Experimental | There is only one arm. Receives: Drug: Bortezomib; pembrolizumab and cisplatin injections--bortezomib followed by pembro/cis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 18 months
Secondary 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;
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2020
- Study start15 Oct 2020
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Baylor Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Health services research
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Baylor Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Joyce O'Shaughnessy, MD, Principal investigator, Texas Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04265872
- Sponsor's protocol ID
- 020-008
- Status last verified
- Feb 2026
- First submitted
- 23 Jan 2020
- Last updated
- 12 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04265872
- Acronym / sponsor ID
- 020-008
- Conditions
- Breast Cancer
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Baylor Research InstituteUniversity, hospital or other
- Study start
- 15 Oct 2020 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Mar 2027 (estimated)
- First posted
- 12 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 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 design
- Primary purpose
- Health services research
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bortezomib followed by pembro/cis | Experimental | Drug: Bortezomib; pembrolizumab and cisplatin injections--bortezomib followed by pembro/cisThere is only one arm. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- A patient will be eligible for inclusion in this study if she meets all of the following criteria:
Key exclusion criteria (22 listed)
- A patient will be ineligible for inclusion in this study if she meets any of the following 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.
- Has a known history of Human Immunodeficiency Virus (HIV)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bortezomib; pembrolizumab and cisplatin injections--bortezomib followed by pembro/cisAlso: Keytruda, Velcade, Platinolinjection into a vein | Drug | Bortezomib followed by pembro/cis |
Primary outcome
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
1 secondary outcome
Calculate response
Time frame: 18 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Joyce O'Shaughnessy, MD principal investigator
Texas Oncology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Bortezomib; pembrolizumab and cisplatin injections--bortezomib followed by pembro/cis in people with Breast Cancer, run by Baylor Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 12 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Page Blas, MA (214-820-5424, page.blas@bswhealth.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Calculate objective response rate (CR+PR) associated with bortezomib followed at disease progression with pembrolizumab and cisplatin in metastatic TNBC (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2026.