NCT05570253招募中2 期
"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
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 55
- 试验地点
- 20
- 主要终点
- change in insulin resistance scores (HOMA-IR)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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) ≤
- •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)
排除标准
- •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
研究组 & 干预措施
Eribulin Plus Placebo
Placebo Comparator
Patients randomized to the control arm will receive placebo plus Eribulin.
干预措施: Eribulin (Drug)
SDX-7320 plus Eribulin
Experimental
Patients randomized to SDX-7320 plus Eribulin.
干预措施: SDX-7320 (Drug)
SDX-7320 plus Eribulin (safety run-in period)
Experimental
During the safety run-in period, the first 15 patients enrolled will be assigned to received study drug SDX-7320 plus Eribulin. Not randomized.
干预措施: SDX-7320 (Drug)
Eribulin Plus Placebo
Placebo Comparator
Patients randomized to the control arm will receive placebo plus Eribulin.
干预措施: Placebo (Other)
SDX-7320 plus Eribulin (safety run-in period)
Experimental
During the safety run-in period, the first 15 patients enrolled will be assigned to received study drug SDX-7320 plus Eribulin. Not randomized.
干预措施: Eribulin (Drug)
SDX-7320 plus Eribulin
Experimental
Patients randomized to SDX-7320 plus Eribulin.
干预措施: Eribulin (Drug)
结局指标
主要结局
change in insulin resistance scores (HOMA-IR)
时间窗: 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).
次要结局
- Type, frequency and severity of treatment-emergent adverse events(2 years)
- Overall response rate(1 year)
研究者
研究点 (20)
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