Bortezomib Followed by Pembrolizumab and Cisplatin in metTNBC

NCT04265872 | Recruiting Early Phase 1 FDA Drug

• 1 other identifier: 020-008
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer

Outcome Measures

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

  18 months

Secondary Outcomes (1)

• Calculate response

  18 months

Other Outcomes (1)

• evaluate research biopsy for homologous recombination deficiency via Next Generation Sequencing

  18 months

Study Arms (1)

Bortezomib followed by pembro/cis

EXPERIMENTAL

There is only one arm.

Drug: Bortezomib; pembrolizumab and cisplatin injections--bortezomib followed by pembro/cis

Interventions

Bortezomib; pembrolizumab and cisplatin injections--bortezomib followed by pembro/cis DRUG

injection into a vein

Also known as: Keytruda, Velcade, Platinol

Bortezomib followed by pembro/cis

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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:
• a. Serum creatinine ≤1.5 x ULN or calculated creatinine clearance of ≥30 mL/min
• Have adequate coagulation function, defined by:

You may not qualify if:

• 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
• 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:

Sponsors & Collaborators

• Baylor Research Institute: lead

Study Sites (1)

Baylor University Medical Center, Baylor Charles A Sammons Cancer Center

Dallas, Texas, 75246, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Bortezomib; pembrolizumab; Cisplatin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorine Compounds; Nitrogen Compounds; Platinum Compounds

Study Officials

• Joyce O'Shaughnessy, MD

  Texas Oncology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Page Blas, MA

CONTACT

214-820-5424; page.blas@bswhealth.org

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2020
• First Posted: February 12, 2020
• Study Start: October 15, 2020
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): March 31, 2027
• Last Updated: February 12, 2026

Record last verified: 2026-02

Locations

US (1)