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New treatment option for Anatomic Stage III Breast Cancer AJCC v8
Official title Testing the Addition of Anti-Cancer Drug, ZEN003694 (ZEN-3694) and PD-1 Inhibitor (Pembrolizumab), to Standard Chemotherapy (Nab-Paclitaxel) Treatment in Patients With Advanced Triple-Negative Breast Cancer
ClinicalTrials.gov ID: NCT05422794
What this study is testing
What is BET Bromodomain Inhibitor ZEN-3694?
BET Bromodomain Inhibitor ZEN-3694 is an investigational medicine, given as an once-daily infusion into a vein, being studied as a potential treatment for anatomic stage iii breast cancer ajcc v8.
Also referred to as BETi ZEN-3694, ZEN 3694.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- This phase Ib trial tests the safety and tolerability of ZEN003694 in combination with an immunotherapy drug called pembrolizumab and the usual chemotherapy approach with nab-paclitaxel for the treatment of patients with triple negative-negative breast cancer that has spread to other parts of the body (advanced). Paclitaxel is in a class of medications called antimicrotubule agents.
- Phase 1: an early, usually small safety study
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- Participants must have a histologically or cytologically confirmed diagnosis of TNBC based on standard criteria for the disease:
- Estrogen receptor (ER) and progesterone receptor (PR) \< 10% by immunohistochemistry (IHC), and HER2-negative (per current American Society of...
- If there is more than one histological result available, the most recent sample with ER, PR and HER2 results will be considered for inclusion
- Patients who have not had ER, PR and HER2 testing and thus, ER, PR and HER2 status is unknown, are not eligible
- Participants without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis from physical...
You likely can't join if
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ZEN003694 (ZEN-3694), nab-paclitaxel, or...
- Patients with uncontrolled intercurrent illness
- Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents...
- Any gastrointestinal (GI) disorder that may affect absorption of oral medications in the opinion of the treating investigator, such as malabsorption...
- Pregnant women are excluded from this study because ZEN003694 (a BETi agent) and MK-3475 have the potential for teratogenic or abortifacient effects...
- Patients who have previously received ZEN003694 (ZEN-3694) or who have been treated with an investigational BET inhibitor
See the full eligibility criteria
Who can join
- Participants must have a histologically or cytologically confirmed diagnosis of TNBC based on standard criteria for the disease:
- Estrogen receptor (ER) and progesterone receptor (PR) \< 10% by immunohistochemistry (IHC), and HER2-negative (per current American Society of Clinical Oncology [ASCO]/College of American Pathologists [CAP] guidelines)
- If there is more than one histological result available, the most recent sample with ER, PR and HER2 results will be considered for inclusion
- Patients who have not had ER, PR and HER2 testing and thus, ER, PR and HER2 status is unknown, are not eligible
- Participants without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis from physical examination or radiologic evaluation
- Participants must have disease that is unresectable locally advanced or metastatic
- DOSE ESCALATION COHORT: Known PD-L1 status is not required prior to study enrollment. Central PD-L1 testing (on archival tumor tissue) will occur retrospectively
- DOSE ESCALATION COHORT: Any number of prior lines of therapy are allowed in the metastatic setting. Prior immune checkpoint inhibitor allowed in any setting
- DOSE ESCALATION COHORT: Evaluable or measurable disease per RECIST 1.1 criteria
- DOSE EXPANSION COHORT: PD-L1 status must be negative. Standard local testing with any PD-L1 antibody that has been validated in a Clinical Laboratory Improvement Act (CLIA)- certified environment will be acceptable for...
- DOSE EXPANSION COHORT: 0-1 prior lines of systemic therapy in the metastatic setting
- DOSE EXPANSION COHORT: Participants must have measurable disease per RECIST 1.1 criteria
- DOSE EXPANSION COHORT: Participants must have disease that is amenable to biopsy as judged by the treating investigator and must be willing to undergo pre- and on-treatment tumor biopsies, if safely accessible
- Age \>= 18 years
- Because no dosing or adverse event data are currently available on the use of ZEN003694 (ZEN-3694) in combination with nab-paclitaxel and pembrolizumab (MK-3475) in patients \< 18 years of age, children are excluded...
- Eastern Cooperative Oncology Group (ECOG) performance status =\ = 60%)
- Absolute neutrophil count \>= 1,000/mcL
- Platelets \>= 100,000/mcL
- Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L
- Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (or =\< 2.0 x ULN in patients with documented Gilbert's Syndrome)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) / alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =\< 3.0 x institutional ULN or ≤ 5.0 x institutional ULN...
- Serum or plasma creatinine =\ = 60 mL/min (based on the calculated chronic kidney disease epidemiology (CKD-EPI) glomerular filtration rate estimation
- International normalized ratio (INR) or prothrombin time (PT): =\< 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended...
- Activated partial thromboplastin time (aPTT): =\< 1.5 × ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial as long as their anti-retroviral therapy does not have...
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
- Patients with history of treated central nervous system (CNS) metastases are eligible, provided they meet the following criteria:
- Disease outside the CNS is present
- Recovery from acute toxicity associated with the treatment to =\< Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 1 or baseline (with the exception of alopecia), with no requirement for...
- Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is...
- Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or how well it works assessment of the investigational regimen are eligible for...
- Patients should be New York Heart Association Functional Classification of class 2B or better
- Peripheral neuropathy grade =\< 1
- Ability to swallow and retain oral medications
- Participants may not have had cytotoxic chemotherapy, immunotherapy, major surgery (other than diagnostic surgery, dental surgery or stenting), or other investigational therapy within 3 weeks prior to entering the study
- Participants may not have had radiotherapy within 1 week prior to entering the study. Patients may not have had \> 25% of their bone marrow radiated. Stereotactic radiosurgery (SRS) within 1 week prior to entering the...
- Participants may not have received tyrosine kinase inhibitors (TKIs) or small molecules within 5 half-lives or 2 weeks (whichever is shorter) of study entry
- Patients who have experienced adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) must have recovered, with the exception of alopecia or as otherwise specified in the eligibility...
- The effects of the combination of ZEN003694 (ZEN-3694) and MK-3475 on the developing human fetus are unknown. For this reason and because BETi and PD-1 blocking agents as well as other therapeutic agents used in this...
- Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity who have a legally-authorized representative (LAR) and/or family member...
What rules you out
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ZEN003694 (ZEN-3694), nab-paclitaxel, or pembrolizumab
- Patients with uncontrolled intercurrent illness
- Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine...
- Any gastrointestinal (GI) disorder that may affect absorption of oral medications in the opinion of the treating investigator, such as malabsorption syndrome or major bowel or stomach resection
- Pregnant women are excluded from this study because ZEN003694 (a BETi agent) and MK-3475 have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in...
- Patients who have previously received ZEN003694 (ZEN-3694) or who have been treated with an investigational BET inhibitor
- DOSE EXPANSION COHORT: Prior exposure to immune checkpoint inhibitors in the metastatic setting. PD-1 or PD-L1 inhibitors in the neo-/adjuvant setting are allowed if at least 12 months have elapsed since the end of...
- DOSE EXPANSION COHORT: Prior exposure to taxane-based therapy in the metastatic setting. Taxane in the neo-/adjuvant setting is allowed if at least 12 months have elapsed since the end of adjuvant systemic treatment to...
- Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 are ineligible. Strong inhibitors or inducers of CYP3A4 must be discontinued at least 7 days prior to the first dose of...
- Patients receiving any medications or substances that are Factor Xa inhibitors (i.e., rivaroxaban, apixaban, betrixaban, edoxaban otamixaban, letaxaban, eribaxaban) and Factor IIa inhibitors (i.e., dabigatran). Low...
- Patients who have had a bone-targeted radionuclide within 6 weeks of the first dose of ZEN003694 (ZEN-3694)
- Myocardial infarction or unstable angina within 6 months prior to the first dose of ZEN003694 (ZEN-3694)
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. The use of physiologic doses of...
- Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
- Has a known history of active tuberculosis (TB)
- Has received a live vaccine within 30 days of planned treatment start. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, Bacille...
- Participants with known or suspected extensive bone marrow infiltration per radiographic assessment, laboratory assessment, or bone marrow sampling (e.g., aspiration or biopsy), determined to be clinically significant...
The study team makes the final eligibility decision.
Where it's taking place
- Boston, Massachusetts, United States
- Mineola, New York, United States
- New York, New York, United States
- Columbus, Ohio, United States
- Nashville, Tennessee, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Boston, Massachusetts, United States; Mineola, New York, United States; New York, New York, United States; Columbus, Ohio, United States; Nashville, Tennessee, United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.