Investigator-Initiated Phase 2 Clinical Trial of Selinexor (KPT-330) for the Treatment of Metastatic Triple Negative Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Clinical Benefit Rate
研究概览
简要总结
The main purpose of this study is to see whether the combination of selinexor (KPT-330) can help people with triple negative breast cancer (TNBC). Researchers also want to study the safety and tolerability of Selinexor in TNBC patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Histologically confirmed triple negative breast cancer (TNBC), defined as negative immunohistochemical staining for estrogen and progesterone receptors (≤5% of nuclei positive by IHC) and receptor tyrosine-protein kinase erbB-2 (HER2) negative (IHC 0-1+ or HER2-neu negative according to American Society of Clinical Oncology; College of American Pathologists (ASCO-CAP) HER2 Test Guideline Recommendations)
- •Written informed consent in accordance with federal, local, and institutional guidelines
- •Body surface area ≥1.4 m^2
- •Age ≥18 years
- •Estimated life expectancy of >3 months at study entry
- •TNBC must be either locally recurrent or metastatic. Locally recurrent disease must not be amenable to surgical resection or radiation with curative intent.
- •Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
- •Documented disease progression at study entry
- •Must have received at least 1 chemotherapy regimens in the setting of metastatic disease
- •Eastern Cooperative Oncology Group (ECOG) performance status of ≤2
- •Adequate hematological function: Absolute neutrophil count (ANC) > 1500/mm^3, platelets count >100,000mm^3
- •Adequate hepatic function within 14 days prior to Cycle 1 Day 1 (C1D1): total bilirubin <2 times the upper limit of normal (ULN) (except patients with Gilbert's syndrome who must have a total bilirubin of < 3 times ULN) and aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤2.5 x ULN. In the case of known (radiological and/or biopsy documented) liver metastasis, AST/ALT ≤5.0 times ULN is acceptable.
- •Amylase and lipase ≤ 1.5 x ULN
- •Adequate renal function within 14 days prior to C1D1: estimated creatinine clearance of ≥ 30 mL/min
- •Women of child-bearing potential (WOCBP) must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and male participants must use an effective barrier method of contraception if sexually active with a female of child-bearing potential. For both male and female participants, effective methods of contraception must be used throughout the study and for 3 months following the last dose. To be considered of non-childbearing potential, postmenopausal women must be amenorrheic for at least 12 months naturally (not in the setting of post chemotherapy) or participants must be surgically sterile.
- •Must have received prior anthracycline and taxane therapy unless clinically contraindicated
排除标准
- •Significant medical illness that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the participant's ability to tolerate this therapy
- •Women who are pregnant or lactating
- •Radiation, chemotherapy, or immunotherapy or any other approved anticancer therapy ≤2 weeks prior to cycle 1 day 1
- •Major surgery within 4 weeks before Day 1
- •Unstable cardiovascular function: Electrocardiogram (ECG) abnormalities requiring treatment, or congestive heart failure (CHF) of New York Hearth Association (NYHA) Class ≥3; myocardial infarction (MI) within 3 months
- •Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose. Potential participants with controlled infection or on prophylactic antibiotics are permitted in the study.
- •Known history of HIV
- •Known active hepatitis A, B, or C infection that requires treatment
- •Any underlying condition that would significantly interfere with the absorption of an oral medication
- •Grade >2 peripheral neuropathy at baseline (within 14 days prior to cycle 1 day 1)
- •Participation in an investigational anti-cancer study within 3 weeks prior to Cycle 1 Day 1
- •Coagulation problems and active major bleeding within 4 weeks prior to C1D1 (peptic ulcer, epistaxis, spontaneous bleeding)
- •Active central nervous system (CNS) malignancy. Asymptomatic small lesions are not considered active. Treated lesions may be considered inactive if they are stable for at least 3 months.
- •Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤ 2 weeks prior to Cycle 1 Day 1 or radio-immunotherapy ≤ 4 weeks prior to Cycle 1 Day 1
- •Have not recovered to Grade ≤ 1 or to their baseline from clinically significant adverse effects
研究组 & 干预措施
Selinexor Treatment
Screening period (which may last up to 28 days), followed by Selinexor treatment for qualified participants.
During the treatment period, participants will undergo physical examination every 2 weeks until Cycle 6 Day 1 (C6D1), and then every 4 weeks and assessment of tumor response every 8 weeks.
Participants will be treated until progression of disease or the development of unacceptable toxicities. All participants will then undergo a final visit (end of treatment visit).
干预措施: Selinexor (Drug)
结局指标
主要结局
Clinical Benefit Rate
时间窗: Up to 10 months
Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) ≥ 12 weeks of selinexor in patients with triple negative breast cancer (TNBC), according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of the diameter (LD) of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
次要结局
- Progression-Free Survival (PFS)(Up to 10 months)
- Duration of Overall Response(Up to 10 months)
- Best Overall Response (OR)(Up to 10 months)
- Overall Survival (OS)(End of post-treatment 12 month follow-up, up to 24 months per participant)