RECRUITING

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

Conditions

Breast Cancer Metastatic Triple-Negative Breast Cancer Evexomostat (SDX-7320)Eribulin 22-074

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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

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.

Official Title

"A Phase 2, Double Blinded, Randomized Controlled Trial of Evexomostat (SDX-7320) or Placebo in Combination With Eribulin for Patients With Metastatic Triple-Negative Breast Cancer and Metabolic Dysfunction: The ARETHA Study

Quick Facts

Study Start:2022-10-03

Study Completion:2027-10

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05570253

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 Criteria	Exclusion 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+ (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 central 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 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 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)	* 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 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) * Child Pugh score of B or C. * 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. * 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

Inclusion Criteria

Exclusion 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+ (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 central 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 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 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)

* 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 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)
* Child Pugh score of B or C.
* 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.
* 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

Contacts and Locations

Study Contact

Neil Iyengar, MD

CONTACT

646-888-8103

iyengarn@mskcc.org

Tiffany Trainia, MD

CONTACT

646-888-4558

Principal Investigator

Neil Iyengar, MD

PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Study Locations (Sites)

BAPTIST ALLIANCE - MCI (Data Collection Only)

Miami, Florida, 33143

United States

Memorial Sloan Kettering Basking Ridge (All Protocol Activities)

Basking Ridge, New Jersey, 07920

United States

Memorial Sloan Kettering Monmouth (All Protocol Activities)

Middletown, New Jersey, 07748

United States

Memorial Sloan Kettering Bergen (All Protocol Activities)

Montvale, New Jersey, 07645

United States

Memorial Sloan Kettering Suffolk - Commack (All Protocol Activities)

Commack, New York, 11725

United States

Memorial Sloan Kettering Westchester (All Protocol Activities)

Harrison, New York, 10604

United States

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065

United States

Memorial Sloan Kettering Nassau (All Protocol Activities)

Uniondale, New York, 11553

United States

Collaborators and Investigators

Sponsor: Memorial Sloan Kettering Cancer Center

Neil Iyengar, MD, PRINCIPAL_INVESTIGATOR, Memorial Sloan Kettering Cancer Center

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 Date2022-10-03

Study Completion Date2027-10

Study Record Updates

Study Start Date2022-10-03

Study Completion Date2027-10

Terms related to this study

Keywords Provided by Researchers

Evexomostat (SDX-7320)
Eribulin
22-074

Additional Relevant MeSH Terms

Breast Cancer
Metastatic Triple-Negative Breast Cancer