Dysautonomia International

A Study of SDX-7320 in Combination With Eribulin for People With Breast Cancer

Purpose

The researchers are doing this study to find out whether the study drug, SDX-7320, when combined with the standard chemotherapy eribulin, is an effective treatment for people with TNBC and metabolic dysfunction. The researchers will also look at whether the study treatment (SDX-7320 combined with eribulin) is safe and causes few or mild side effects in participants. The researchers will compare this treatment approach to eribulin alone.

Conditions

Breast Cancer
Metastatic Triple-Negative Breast Cancer

Eligibility

Eligible Ages: Over 18 Years
Eligible Sex: All
Accepts Healthy Volunteers: No

Inclusion Criteria

Male or female with histologically and/or cytologically confirmed diagnosis of triple-negative metastatic breast cancer defined as estrogen and progesterone receptor staining ≤10%; and HER2-negative defined as IHC 0 to 1+ at enrolling institution (note: if IHC is equivocal, non-amplified status by FISH is acceptable) - Advanced (local regionally recurrent, not amenable to curative therapy or surgery) or metastatic stage with up to 2 prior lines of therapy in the advanced or metastatic setting - Received prior anthracycline and taxane chemotherapy in the neoadjuvant, adjuvant, or metastatic settings and considered appropriate for treatment with single agent eribulin OR was otherwise ineligible to receive anthracycline and/or taxane per treating physician OR patients with de novo metastatic disease. - Evidence of metabolic dysfunction defined as HbA1c > 5.5 and/or BMI ≥ 30 kg/m^2 - Measurable disease per the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), OR at least one evaluable, predominantly lytic bone lesion - Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ≤1. - Adult ≥18 at the time of informed consent and has provided written informed consent before the performance of any study-related activities and according to local guidelines. - Adequate bone marrow and organ function as defined by the following laboratory values (as assessed by local laboratory for eligibility): - Absolute neutrophil count (ANC) ≥ 1,000 µL - Platelet count ≥ 140,000 µL - Hemoglobin ≥9.0 g/dL: - Calcium (corrected for serum albumin) and magnesium ≤ Grade 1 according to National Cancer Institute (NCI) Common Terminology - Calculate Corrected Calcium if the albumin and/or serum calcium are not within normal limits: Corrected Calcium= Serum Calcium + 0.8 x [(Normal Albumin) - Patient Albumin] Normal Albumin value = 4.4g/dL Criteria for Adverse Events (CTCAE), version 5.0, and not considered by the Investigator to be clinically significant - Potassium within normal limits, with or without correction with supplements. - In absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×the upper limit of normal (ULN). If the patient has liver metastases, ALT and AST ≤5×ULN. - Total bilirubin ≤1.5×ULN except for patient with Gilbert's syndrome who may only be included if the total bilirubin is ≤3.0×ULN or direct bilirubin ≤1.5×ULN - Creatinine ≤1.5 mg/dL. - Patient is, in the treating Investigator's opinion, willing and able to comply with the study requirements, including the ability to fast prior to treatment days. - If sexually active female of childbearing potential, willing to use a contraception method listed below: - Oral, intravaginal, or transdermal combined (estrogen and progesterone containing) hormonal contraception - Oral, injectable, or implantable progesterone-only hormonal contraception - Intrauterine device (IUD) - Intrauterine hormone-releasing system (IUS) - Bilateral tubal occlusion - Vasectomized partner with documentation of successful vasectomy. - Complete abstinence from heterosexual intercourse - If a sexually active male, willing to use barrier contraception (condoms)

Exclusion Criteria

Three or greater prior lines of therapy for metastatic TNBC - Known primary brain malignancy, brain metastases or active CNS pathology, any of which as determined by the treating Investigator - Currently participating in a study of an investigational agent - Body mass index < 18.5 kg/m2 - Known hypersensitivity to SDX-7320 or eribulin - Established diagnosis of diabetes mellitus type I or uncontrolled or insulin-dependent type II. Uncontrolled is defined as fasting blood glucose >140 mg/dL and/or HbA1c ≥8% - Use of combination antihyperglycemic therapy (single agent metformin on stable dose for at least 3 months prior to enrollment is allowable) - Concurrent malignancy or malignancy within 3 years of randomization, with the exception of adequately treated, basal or squamous cell carcinoma, nonmelanomatous skin cancer or curatively resected cervical cancer. - Uncontrolled human immunodeficiency virus (HIV) infection. (Testing is not mandatory.) - Evidence of uncontrolled active Hepatitis B or C infection - History of Stevens-Johnson Syndrome (SJS), erythema multiforme (EM), toxic epidermal necrolysis (TEN), or other severe medication-related cutaneous reactions. - Any other concurrent severe and/or uncontrolled medical condition that would, in the Investigator's judgment, contraindicate patient participation in the clinical study (e.g., chronic active hepatitis, severe hepatic impairment). - Clinically significant, uncontrolled heart disease and/or recent cardiac events including any of the following: - History of angina pectoris, coronary artery bypass graft (CABG) symptomatic pericarditis, or myocardial infarction within 6 months prior to study entry. - History of documented congestive heart failure (New York Heart Association functional classification III-IV). - Documented cardiomyopathy. - Left ventricular ejection fraction (LVEF) <45%, as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO). - History of any cardiac arrhythmias, (e.g., ventricular tachycardia), complete left bundle block, high grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third-degree AV block) supraventricular, nodal arrhythmias, or conduction abnormality in the previous 12 months. - Uncontrolled hypertension, defined by a systolic blood pressure (SBP) ≥160 mmHg and/or diastolic blood pressure (DBP) ≥100 mmHg, with or without antihypertensive medication. Initiation or adjustment of antihypertensive medication(s) is allowed prior to screening - Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome or any of the following: risk factors for torsades de pointe including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure or history of clinically significant/symptomatic bradycardia; concomitant medications with a known risk to prolong the QT interval and known to cause torsades de pointe that cannot be discontinued or replaced by safe alternative medications. - Bradycardia (heart rate less than 50 at rest), by electrocardiogram (ECG) or pulse. - Inability to determine the QT interval on the ECG (i.e., unreadable or not interpretable) or corrected QT (QTcF) >450 msec for males and >470 msec for females (using Fridericia's correction) during Screening, based on the mean of triplicate ECGs - Currently receiving any of the following medications and cannot be discontinued 7 days prior to the start of the treatment: Medications with a known risk to prolong the QT interval or induce Torsade de Pointes (TdP). CredibleMeds list of drugs known to cause TdP may be used as a reference for this study to determine which drugs are prohibited using the following link: https://crediblemeds.org/new-drug-list or a crediblemeds mobile application. °Herbal preparations/medications, with the exception of cannabinoids, CBD compounds, etc. - Participation in a prior investigational study within 14 days prior to the start of the study treatment or within 5 half-lives of study drug, whichever is longer. - History of acute pancreatitis within 1 year of Screening or past medical history of chronic pancreatitis - Pregnant patients

Study Design

Phase: Phase 2
Study Type: Interventional
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: This is a multi-center, placebo-controlled phase 2 randomized control trial.
Primary Purpose: Treatment
Masking: Triple (Participant, Care Provider, Investigator)

Arm Groups

Arm	Description	Assigned Intervention
Experimental SDX-7320 plus Eribulin (safety run-in period)	During the safety run-in period, the first 15 patients enrolled will be assigned to received study drug SDX-7320 plus Eribulin. Not randomized.	Drug: Eribulin Eribulin 1.4 mg/m2 IV on days 1 and 8 of an every 21 day cycle. Drug: SDX-7320 SDX-7320 at the dose of 49 mg/m2 SC on a Q14D basis
Experimental SDX-7320 plus Eribulin	Patients randomized to SDX-7320 plus Eribulin.	Drug: Eribulin Eribulin 1.4 mg/m2 IV on days 1 and 8 of an every 21 day cycle. Drug: SDX-7320 SDX-7320 at the dose of 49 mg/m2 SC on a Q14D basis
Placebo Comparator Eribulin Plus Placebo	Patients randomized to the control arm will receive placebo plus Eribulin.	Drug: Eribulin Eribulin 1.4 mg/m2 IV on days 1 and 8 of an every 21 day cycle. Other: Placebo Placebo

Recruiting Locations

BAPTIST ALLIANCE - MCI (Data Collection Only)
Miami, Florida 33143

Contact:
Lauren Carcas, MD
954-837-1490

Emory University (Data Collection Only)
Atlanta, Georgia 30322

Contact:
Neil Iyengar, MD
404-778-1900

Memorial Sloan Kettering Basking Ridge (All Protocol Activities)
Basking Ridge, New Jersey 07920