RECRUITING

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

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Conditions

Anatomic Stage III Breast Cancer AJCC v8Anatomic Stage IV Breast Cancer AJCC v8Metastatic Triple-Negative Breast CarcinomaUnresectable Triple-Negative Breast Carcinoma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

Phase I Study Targeting DNA Methyltransferases in Metastatic Triple-Negative Breast Cancer

Quick Facts

Study Start:2023-09-25
Study Completion:2027-02-23
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT05673200

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * 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
  2. * 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
  3. * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (or Karnofsky \>= 60%)
  4. * Absolute neutrophil count (ANC) \>= 1500/mm\^3 (within 14 days prior to registration)
  5. * Platelets \>= 100,000/mm\^3 (within 14 days prior to registration)
  6. * Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L (within 14 days prior to registration)
  7. * 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)
  8. * Creatinine clearance (CrCl) \>= 30 mL/min (within 14 days prior to registration)
  9. * Glomerular filtration rate (GFR) can also be used in place of CrCl
  10. * 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)
  11. * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase \[SGPT\]) =\< 3 x institutional ULN (within 14 days prior to registration)
  12. * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  13. * 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
  14. * Patients with treated brain metastases are eligible if there is evidence of measurable extracranial disease, and if follow-up brain imaging 4 weeks after central nervous system (CNS)-direct therapy shows no evidence of progression. Patients with carcinomatous meningitis are not eligible.
  15. * Patients with a prior malignancy whose natural history does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Concurrent use of other antineoplastic treatments is not allowed.
  16. * Patients should be New York Heart Association Functional Classification of class II or better.
  17. * Patients who have received live attenuated vaccines within the 30 days prior to registration are not eligible. Seasonal flu vaccines that do not contain live virus, and coronavirus disease 2019 (COVID-19) vaccinations and boosters are permitted.
  18. * Patients with prior history of peripheral neuropathy are allowed if it has recovered to grade 1 or less.
  19. * Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial.
  20. * Patients who have received 0-3 prior lines of chemotherapy in the metastatic setting. Patients who have received prior PD-1/PD-L1 monoclonal antibodies in any disease setting are eligible.
  21. * For enrollment to Dose Finding Cohort: Availability and willingness to provide archival tumor tissue as required per protocol.
  22. * For enrollment to Dose Expansion Cohort: (i) Willingness to provide baseline and 3-week tumor tissue biopsy specimens. (ii) Patients must have a measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
  23. * The effects of ASTX727 and pembrolizumab (MK-3475) on the developing human fetus are unknown. For this reason and because these agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 180 days after the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Pregnant women are excluded from this study because pembrolizumab (MK-3475) is an anti PD-1 monoclonal antibody agent, ASTX727 is a hypomethylating agent, and paclitaxel is a class D agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with pembrolizumab (MK-3475), breastfeeding should be discontinued if the mother is treated with pembrolizumab (MK-3475). These potential risks may also apply to other agents used in this study. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 180 days after completion of study treatment.
  24. * Ability to understand and the willingness to sign a written informed consent document (or have legally acceptable representative sign, if applicable).
  25. * Patients who have recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia.
  26. * Note: If patients received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  27. * Has not received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including granulocyte colony-stimulating factor \[G-CSF\], granulocyte macrophage colony-stimulating factor \[GM-CSF\], or recombinant erythropoietin) within 4 weeks prior to registration.
  1. * Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within the 7 days prior to registration.
  2. * Has a known additional malignancy that is progressing or requires active treatment.
  3. * Has an active autoimmune disease that has required systemic treatment within 2 years prior to registration (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Current treatment with systemic steroids up to 10 mg of prednisone daily or equivalent is allowed.
  4. * Patients with uncontrolled intercurrent illness (including but not limited to interstitial lung disease or active, non-infectious pneumonitis) or a history of (non-infectious) pneumonitis that required steroids.
  5. * History of grade 3-4 immediate hypersensitivity reaction to paclitaxel or other drugs formulated in polyoxyl 35 castor oil.
  6. * Patients who are receiving any other investigational agents.
  7. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to ASTX727, pembrolizumab (MK-3475), and/or paclitaxel.
  8. * Has a known history of active tuberculosis (TB).
  9. * Gastrointestinal disorder that may impact absorption of oral medications.
  10. * History of solid organ or bone marrow transplantation.

Contacts and Locations

Principal Investigator

Roberto A Leon-Ferre
PRINCIPAL_INVESTIGATOR
Dana-Farber - Harvard Cancer Center LAO

Study Locations (Sites)

Mayo Clinic Hospital in Arizona
Phoenix, Arizona, 85054
United States
UC Irvine Health Cancer Center-Newport
Costa Mesa, California, 92627
United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868
United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
United States
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980
United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232
United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298
United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

  • Roberto A Leon-Ferre, PRINCIPAL_INVESTIGATOR, Dana-Farber - Harvard Cancer Center LAO

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-09-25
Study Completion Date2027-02-23

Study Record Updates

Study Start Date2023-09-25
Study Completion Date2027-02-23

Terms related to this study

Additional Relevant MeSH Terms

  • Anatomic Stage III Breast Cancer AJCC v8
  • Anatomic Stage IV Breast Cancer AJCC v8
  • Metastatic Triple-Negative Breast Carcinoma
  • Unresectable Triple-Negative Breast Carcinoma