Clinical Trial of Avasopasem in Patients With Metastatic Hormone Receptor Positive Breast Cancer With Progression on a CDK 4/6 Inhibitor and Hormonal Therapy

* Patient may have been on palbociclib previously but must have been stable on ribociclib or abemaciclib for at least three months prior to enrolling. In this case, the switch from palbociclib to either ribociclib or abemaciclib must have been of toxicity management and not progression of disease.

* Hormonal therapy is defined as an aromatase inhibitor (anastrozole, letrozole, exemestane) or fulvestrant.

* Both men and pre/perimenopausal women must be on ovarian suppression with a luteinizing hormone-releasing hormone (LHRH) agonist.

Patients must have measurable disease based on RECIST 1.1 criteria.

Females of child-bearing potential (FOCBP) who engage in intercourse must agree to use adequate contraception (e.g., hormonal or an intrauterine device \[IUD\] or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 3 weeks following completion of therapy.

NOTE: A FOCBP is any woman who meets the following criteria:

Has not undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy

Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for \> 12 months)

* FOCBP must have a negative serum pregnancy test within 7 days prior to registration.

* Patients must be ≥ 18 years of age at the time of signing consent.

* Patients must have an estimated life expectancy of at least 12 weeks.

* Patients must exhibit an ECOG performance status of 0 or 1.

* Patients must have adequate organ and bone marrow function as defined below:

* Leukocytes (WBC) ≥ 3,000/mcL

* Absolute neutrophil count (ANC) ≥ 1000/mcL

* Hemoglobin (Hgb) ≥ 7 g/dL

* Platelets (PLT) ≥ 100,000/mcL

* Total bilirubin \< 1.5 x Institutional upper limit of normal (ULN); ≤ 3.0 x ULN for patients with Gilbert's syndrome

* AST (SGOT)/ALT (SGPT) \< 3 x institutional ULN, or \< 5 x ULN if liver metastasis present

* Creatinine \< 1.5 Institutional ULN

Patients who have any systemic therapy in the metastatic setting except hormonal therapy in combination with a CDK 4/6 inhibitor. Previously palliative targeted radiation therapy is allowed. Bone targeting agents such as bisphosphonates and rank ligand inhibitors for metastatic breast cancer to the bone is also allowed prior and during this trial.

Patients with untreated new or progressive brain metastases or leptomeningeal disease

Use of concomitant nitrates and PDE5 inhibitors.

Use of potent CYP3A4 inhibitors or inducers and not able to discontinue two weeks prior to enrolling onto the trial.

Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints. Note: Patients with HIV or infectious hepatitis must exhibit well controlled disease with stable treatment regimen (where applicable) that in the opinion of the treating physician should not preclude them from participating in the study.

Patients who are currently pregnant or breast feeding.

Patients with a history of another invasive malignancy within 2 years of registration with the exception of local squamous cell or basal cell carcinoma of the skin.

What this study is about