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

Official 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.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 32 participants

Interventions

• PROCEDURE: Biopsy Procedure — Undergo biopsy
• PROCEDURE: Biospecimen Collection — Undergo collection of blood
• PROCEDURE: Computed Tomography — Undergo CT
• DRUG: Decitabine and Cedazuridine — Given PO
• PROCEDURE: Magnetic Resonance Imaging — Undergo MRI

Primary Outcomes

• Maximally tolerated dose (MTD) of ASTX727 in combination with paclitaxel and pembrolizumab (MK-3475) (Dose Finding Phase) (Within the first cycle of treatment (28 days))
• Safety profile of ASTX727 in combination with paclitaxel and pembrolizumab (MK-3475) (Dose Finding Phase) (Up to 4 years)

Secondary Outcomes

• Tolerability (Dose Expansion Phase) (Upon completion of the dose expansion phase)
• Tumor response rate (Dose Expansion Phase) (Up to 4 years)
• Duration of response (Dose Expansion Phase) (From the time measurement criteria are met for CR or PR until the first date that recurrent or progressive disease is objectively documented, assessed up to 4 years)
• Overall survival (Dose Expansion Phase) (From study entry to death due to any cause, assessed up to 4 years)
• Progression-free survival (Dose Expansion Phase) (From study entry to the documentation of disease progression, assessed up to 4 years)

Trial Locations

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

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