"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
概览
- 阶段
- 2 期
- 干预措施
- SDX-7320
- 疾病 / 适应症
- Breast Cancer
- 发起方
- Memorial Sloan Kettering Cancer Center
- 入组人数
- 55
- 试验地点
- 21
- 主要终点
- change in insulin resistance scores (HOMA-IR)
- 状态
- 招募中
- 最后更新
- 5天前
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.
研究者
入排标准
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
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
研究组 & 干预措施
SDX-7320 plus Eribulin
Patients randomized to SDX-7320 plus Eribulin.
干预措施: SDX-7320
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.
干预措施: SDX-7320
Eribulin Plus Placebo
Patients randomized to the control arm will receive placebo plus Eribulin.
干预措施: Placebo
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.
干预措施: Eribulin
SDX-7320 plus Eribulin
Patients randomized to SDX-7320 plus Eribulin.
干预措施: Eribulin
Eribulin Plus Placebo
Patients randomized to the control arm will receive placebo plus Eribulin.
干预措施: Eribulin
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)