SuspendedPhase 1

Testing the Addition of an Anti-cancer Drug, ASTX727 (Cedazuridine, Decitabine), to Chemotherapy (Paclitaxel) and Immunotherapy (Pembrolizumab) for Metastatic Triple-Negative Breast Cancer

Stopped: Other - DLT assessment and phase 2 dose determination

United States32 participantsStarted 2023-09-25

Plain-language summary

This phase I trial tests the safety, side effects, and best dose of ASTX727 when given in combination with a usual approach of treatment with paclitaxel and pembrolizumab in patients with triple-negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic). The usual approach is defined as care most people get for this type of cancer. The usual approach for patients with metastatic triple negative breast cancer who are not in a study is chemotherapy with drugs like paclitaxel, carboplatin, cisplatin, eribulin, vinorelbine, capecitabine, gemcitabine, doxorubicin or cyclophosphamide. There is a protein called PD-L1 that helps regulate the body's immune system. For patients who have PD-L1+ tumors, immunotherapy (pembrolizumab) is usually added to paclitaxel or carboplatin/gemcitabine as initial treatment. For patients who have PD-L1-negative tumors, chemotherapy alone is used, without immunotherapy. ASTX727 is a combination of two drugs, decitabine and cedazuridine. Cedazuridine is in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Paclitaxel is in a class of medications called antimicrotubule agents. It stops tumor cells from growing and dividing and may kill them. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving ASTX727 with usual treatment approach with paclitaxel and pembrolizumab may be able to shrink or stabilize the tumor for longer than the usual approach alone in patients with metastatic triple negative breast cancer.

Who can participate

Age range

18 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * Patients must have histologically confirmed triple-negative breast cancer (TNBC) (estrogen receptor \[ER\] and progesterone receptor \[PR\] =\< 10%, human epidermal growth factor receptor-2 \[HER2\]-negative per American Society of Clinical Oncology \[ASCO\]/College of American Pathologists \[CAP\] guidelines) that is metastatic or unresectable * Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of ASTX727 in combination with pembrolizumab (MK-3475) and paclitaxel in patients \< 18 years of age, children are excluded from this study * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (or Karnofsky \>= 60%) * Absolute neutrophil count (ANC) \>= 1500/mm\^3 (within 14 days prior to registration) * Platelets \>= 100,000/mm\^3 (within 14 days prior to registration) * Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L (within 14 days prior to registration) * Criteria must be met without packed red blood cell (pRBC) transfusion within the prior 14 days of registration. Participants can be on stable dose of erythropoietin (90 days or more prior to registration) * Creatinine clearance (CrCl) \>= 30 mL/min (within 14 days prior to registration) * Glomerular filtration rate (GFR) can also be used in place of CrCl * Total bilirubin =\< 1.5 x upper limit of normal (ULN) OR direct bilirubin =\< ULN for patients with total bilirubin levels \> 1.5 × ULN (within 14 days prior to registration) * Aspartate aminotransf…

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Since this is a Phase 1 trial focused on finding the right dose and checking safety of ASTX727 combined with paclitaxel and pembrolizumab, what does that mean for what we know — and don't yet know — about whether this combination actually shrinks tumors in triple-negative breast cancer?
2The trial is combining three different treatments — a hypomethylating agent, chemotherapy, and immunotherapy — which could mean more side effects than any one of them alone; based on my overall health, what risks concern you most for me specifically?
3Are there standard treatment options for metastatic triple-negative breast cancer, like paclitaxel with pembrolizumab alone, that I should consider before looking at an experimental combination like this one?
4How often would I need to come in for treatment and monitoring if I enrolled, and given that this is a dose-finding study where the schedule may be adjusted, how might that affect my day-to-day life?
5If it turns out I experience serious side effects and need to stop the experimental drug ASTX727, would I be able to continue receiving the paclitaxel or pembrolizumab portions of the regimen?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Maximally tolerated dose (MTD) of ASTX727 in combination with paclitaxel and pembrolizumab (MK-3475) (Dose Finding Phase)

Timeframe: Within the first cycle of treatment (28 days)

Safety profile of ASTX727 in combination with paclitaxel and pembrolizumab (MK-3475) (Dose Finding Phase)

Timeframe: Up to 4 years

Trial details

NCT IDNCT05673200

SponsorNational Cancer Institute (NCI)

Sponsor typeNIH

Study typeINTERVENTIONAL

Primary completion2027-02-23

View on ClinicalTrials.gov More Anatomic Stage III Breast Cancer AJCC v8 trials