A Study of SDX-7320 in Combination With Eribulin for People With Breast Cancer
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
The study includes a safety run-in period in which the first 15 patients enrolled will be assigned to receive the study drug SDX-7320 in combination with eribulin. Upon safety confirmation, randomization will commence for the subsequent 40 patients enrolled.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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
|
Outcome Measures
Primary Outcome Measures
- change in insulin resistance scores (HOMA-IR) [1 year]
The Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) is a validated tool for the assessment of insulin resistance.87 HOMA-IR is calculated as follows: fasting serum insulin (μU/mL) × fasting plasma glucose (mmol L -1 )/22.5).
Secondary Outcome Measures
- Type, frequency and severity of treatment-emergent adverse events [2 years]
(TEAEs) and laboratory toxicities per the NCI CTCAE version 5.0.
- Overall response rate [1 year]
Response rate will be assessed by RECIST v1.1
Eligibility Criteria
Criteria
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+ (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
-
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.
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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
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Creatinine ≤1.5 mg/dL.
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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.
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If sexually active female of childbearing potential, willing to use a contraception method listed below:
-
Oral, intravaginal, or transdermal combined (estrogen and progestin containing) hormonal contraception
-
Oral, injectable, or implantable progestin-only hormonal contraception
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Intrauterine device (IUD)
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Intrauterine hormone-releasing system (IUS)
-
Bilateral tubal occlusion
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Vasectomized partner with documentation of successful vasectomy.
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Complete abstinence from heterosexual intercourse
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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 Investigator
-
Currently participating in a study of an investigational agent
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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)
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Child Pugh score of B or C.
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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.
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Uncontrolled human immunodeficiency virus (HIV) infection. (Testing is not mandatory.)
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Evidence of uncontrolled active Hepatitis B or C infection
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History of Stevens-Johnson Syndrome (SJS), erythema multiforme (EM), toxic epidermal necrolysis (TEN), or other severe medication-related cutaneous reactions.
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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.
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History of documented congestive heart failure (New York Heart Association functional classification III-IV).
-
Documented cardiomyopathy.
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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.
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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.
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Bradycardia (heart rate less than 50 at rest), by electrocardiogram (ECG) or pulse.
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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.
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Herbal preparations/medications, with the exception of cannabinoids, CBD compounds, etc.
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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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Memorial Sloan Kettering Basking Ridge (All Protocol Activities) | Basking Ridge | New Jersey | United States | 07920 |
| 2 | Memorial Sloan Kettering Monmouth (All Protocol Activities) | Middletown | New Jersey | United States | 07748 |
| 3 | Memorial Sloan Kettering Bergen (All Protocol Activities) | Montvale | New Jersey | United States | 07645 |
| 4 | Memorial Sloan Kettering Suffolk - Commack (All Protocol Activities) | Commack | New York | United States | 11725 |
| 5 | Memorial Sloan Kettering Westchester (All Protocol Activities) | Harrison | New York | United States | 10604 |
| 6 | Memorial Sloan Kettering Cancer Center (All Protocol Activities) | New York | New York | United States | 10065 |
| 7 | Memorial Sloan Kettering Nassau (All Protocol Activities) | Uniondale | New York | United States | 11553 |
Sponsors and Collaborators
- Memorial Sloan Kettering Cancer Center
- SynDevRx, Inc.
Investigators
- Principal Investigator: Neil Iyengar, MD, Memorial Sloan Kettering Cancer Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 22-074