Bortezomib Followed by Pembrolizumab and Cisplatin in metTNBC
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
Who can join
As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.
- Age
- 18 Years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Compensation
- Not stated
Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.
What to expect
No one can promise a trial will help you personally — that is what the research is trying to find out.
What participation involves
- Procedures mentioned: Biopsies
Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.
Show the study's own words
- "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."
- Compensation
- Not stated
- Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
- Participants are monitored closely by the research team throughout the study.
- Some participants may receive access to an investigational treatment, which is still being studied.
- Your participation helps researchers learn whether this approach could help future patients.
About this study
In plain language
This small study tests bortezomib followed by pembrolizumab and cisplatin when the cancer gets worse. It is for women with triple-negative breast cancer that has spread and has already been treated with chemotherapy. Researchers want to see if bortezomib changes how cancer repairs its DNA, making it more sensitive to the next drugs.
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.
Compensation is read from the study's own description and may be missing — always confirm with the study team.
Eligibility
Who can join
- Women age 18 or older with triple-negative breast cancer that has spread. Some tumors with low estrogen receptor levels may qualify.
- Prior treatment with anthracycline, cyclophosphamide, and taxane chemotherapy. Prior doxorubicin is not required if it was unsafe for you.
- No more than 3 prior chemotherapy treatment plans for cancer that has spread.
- Cancer in the breast, chest wall, nearby lymph nodes, lungs, or liver that can be sampled with a needle. A skin sample may be used instead. If neither is safe, the doctor may still allow you to join.
- Able to do normal activities or light work, with little or no help.
- Blood counts, liver, kidney, and blood-clotting tests must meet study limits.
- If cancer has spread to the brain, it must be treated and not getting worse. You must be off steroids for 2 weeks before bortezomib and no longer need dexamethasone or seizure drugs.
- Able to attend treatment and follow-up visits, understand the study, and sign a consent form.
Who can't join
- A live vaccine within 30 days before treatment; cancer drugs within 4 weeks; or radiation for cancer that has spread within 2 weeks. Other cancer or study treatments are not allowed during this study.
- An immune system disease needing whole-body treatment in the past 2 years, an immune deficiency, or recent immune-suppressing drugs. This includes long-term steroids above 10 mg of prednisone daily. Hormone replacement treatment is allowed.
- Known HIV, hepatitis B, active hepatitis C, a history of active tuberculosis, or an active infection needing whole-body treatment.
- Current lung inflammation, past lung inflammation not caused by infection that needed steroids, or moderate or worse nerve damage.
- Serious heart disease, including a heart attack, certain heart procedures, or sudden heart blood-flow problems within 6 months, or certain levels of heart failure.
- Pregnant or breastfeeding. Anyone who could become pregnant must agree to use effective birth control during the study and for at least 3 months after the last dose.
- Severe or uncontrolled health problems, including very poor lung function, low oxygen levels, liver scarring, or severe liver problems.
- Another active cancer, or any condition, treatment, or test result that the doctor thinks could make the study unsafe, affect its results, or prevent full participation.
Simplified for readability. The official criteria below are what the study team uses.
Official eligibility criteria
Inclusion Criteria: * A patient will be eligible for inclusion in this study if she meets all of the following criteria: 1. Female patients ≥18 years of age 2. 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. 3. 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. 4. 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. 5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (See Appendix I) 6. Have adequate hematologic function, defined by: 1. Absolute neutrophil count (ANC) \>1500/μL 2. Platelet count ≥100,000/μL 3. Hemoglobin ≥9 g/dL or ≥5.6 mmol/L 7. Have adequate liver function, defined by: 1. AST and ALT ≤2.5 x the upper limit of normal (ULN) or ≤5 x ULN in presence of liver metastases 2. Total bilirubin ≤1.5 x ULN OR direct bilirubin ≤ULN for patients with total bilirubin levels \>1.5 × ULN 8. Have adequate renal function, defined by: a. Serum creatinine ≤1.5 x ULN or calculated creatinine clearance of ≥30 mL/min 9. Have adequate coagulation function, defined by: 1. International Normalized Ratio (INR) OR prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤1.5 × ULN. 2. If patient is receiving anticoagulant therapy, PT or aPTT must be within therapeutic range of intended use of anticoagulants. 10. Patients who have a history of brain metastasis are eligible for the study provided that all the following criteria are met: 1. Brain metastases which have been treated 2. Off-treatment with steroids for 2 weeks before administration of the first dose of bortezomib 3. No ongoing requirement for dexamethasone or anti-epileptic drugs 4. No clinical or radiological evidence of progression of brain metastases 11. Patient must be accessible for treatment and follow-up. 12. All patients must be able to understand the investigational nature of the study and give written informed consent prior to study entry. Exclusion Criteria: * EXCLUSION CRITERIA A patient will be ineligible for inclusion in this study if she meets any of the following criteria: 1. 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. 2. 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. 3. 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. 4. Has a known history of Human Immunodeficiency Virus (HIV) 5. 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 6. Has a history of non-infectious pneumonitis that required steroids or current pneumonitis 7. Has peripheral neuropathy ≥grade 2 8. Has completed previous radiotherapy for metastatic disease \<2 weeks prior to study treatment initiation 9. Has an active infection requiring systemic therapy 10. Has significant cardiovascular disease, such as: 1. History of myocardial infarction, acute coronary syndrome, or coronary angioplasty/stenting/bypass grafting within the last 6 months 2. Congestive heart failure (CHF) New York Heart Association (NYHA) Class II-IV, or history of CHF NYHA class III or IV. 11. Has a known history of active tuberculosis 12. 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. 13. Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation such as: 1. 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 2. liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C). 14. 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. 15. 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. 16. Any other investigational or anti-cancer treatments while participating in this study 17. Any other active malignancy
Study sites (1)
TX
- Baylor University Medical Center, Baylor Charles A Sammons Cancer Center · Dallas, TX 75246Joyce O'Shaughnessy, MD · Study contactMore trials in Dallas