A Phase 1 Expansion Cohort Evaluating the Selective Inhibitor of Nuclear Export (SINE) KPT-330 in Patients With Unresectable Melanoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Incidence of adverse events graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03
研究概览
简要总结
This phase I clinical trial studies the side effects of selinexor in treating patients with melanoma that cannot be removed by surgery. Drugs used in chemotherapy, such as selinexor, may stop the growth of tumor cells, by stopping them from dividing.
详细描述
PRIMARY OBJECTIVES:
I. To estimate safety of KPT-330 (selinexor) in patients with melanoma at the maximum tolerated dose (MTD) defined by the phase 1 study.
SECONDARY OBJECTIVES:
I. To determine the clinical benefit rate (CBR) (complete response, partial response, and stable disease) of patients with unresectable melanoma.
II. To assess the efficacy at the MTD as measured by progression free survival (PFS) in patients with melanoma.
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
- •Written informed consent in accordance with federal, local, and institutional guidelines
- •Patients with unresectable melanoma
- •Patients must have received a biologic therapy (e.g. interleukin 2) and a BRAF and/or MEK inhibitor (if tumor contains the V600E or V600K mutation) for 628 metastatic disease. If patient did not receive such agents, rationale for not treating the patients with the 629 agent must be cleared with the study PI (ie no V600e/k BRAF mutation or patient with autoimmunity, thus 630 not eligible for biologic therapy).
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- •Total white blood cell (WBC) count >= 3000/mm^3
- •Absolute neutrophil count (ANC) >= 1500/mm^3
- •Platelet count >= 100,000/mm^3
- •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)
- •Alanine aminotransferase (ALT) < 2.5 times ULN; in the case of known (radiological and/or biopsy documented) liver metastasis, ALT < 5.0 times ULN is acceptable
- •Estimated creatinine clearance of >= 50 mL/min, calculated using the formula of Cockroft and Gault
- •Female patients of child-bearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential; acceptable methods of contraception are condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal; for both male and female patients, effective methods of contraception must be used throughout the study and for three months following the last dose
排除标准
- •Patients who are pregnant or lactating
- •Radiation, chemotherapy, immunotherapy or any other systemic anticancer therapy =< 2 weeks prior to initiation of therapy
- •Major surgery within four weeks before initiation of therapy
- •Unstable cardiovascular function:
- •Symptomatic ischemia, or
- •Uncontrolled clinically significant conduction abnormalities (e.g.: ventricular tachycardia on antiarrhythmics are excluded and 1st degree atrioventricular (AV) block or asymptomatic left anterior fascicular block [LAFB]/right bundle branch block [RBBB] will not be excluded)
- •Congestive heart failure (CHF) of New York Heart Association (NYHA) class >= 3, or
- •Myocardial infarction (MI) within 3 months of initiation of therapy
- •Uncontrolled active infection within one week prior to first dose
- •Known to be human immunodeficiency virus (HIV) seropositive
- •Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus (HCV) ribonucleic acid (RNA) or HBsAg (hepatitis B virus [HBV] surface antigen)
- •Patients with active central nervous system (CNS) malignancy
- •Asymptomatic small lesions are not considered active
- •Treated lesions may be considered inactive if the patient is able to taper off steriods without any recurrent neurologic symptoms.
- •Patients will be excluded if they have had a major resection of the bowel that could influence absorption, inflammatory bowel disease, or other gastrointestinal conditions with increased risk of perforation, history of abdominal fistula, gastrointestinal perforation within 28 days prior to beginning study treatment
- •Grade >= 2 peripheral neuropathy within 14 days prior to initiation of therapy
- •History of seizures, movement disorders or cerebrovascular accident within the past 5 years
- •Patients with known macular degeneration or uncontrolled glaucoma
- •In the opinion of the investigator, patients who are significantly below their ideal body weight
- •Serious psychiatric or medical conditions that could interfere with treatment
- •Participation in an investigational anti-cancer study within 3 weeks prior to initiation of therapy
- •Concurrent therapy with approved or investigational anticancer therapeutic
研究组 & 干预措施
Treatment (selinexor)
Patients receive selinexor PO BIW. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Blood will be collected for correlative studies to perform pK (pharmacokinetics) and pDn (pharmacodynamics) analysis pretreatment on day 1 and 8 hours after treatment, on day 1 of cycles 1 and 2.
干预措施: selinexor (Drug)
Treatment (selinexor)
Patients receive selinexor PO BIW. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Blood will be collected for correlative studies to perform pK (pharmacokinetics) and pDn (pharmacodynamics) analysis pretreatment on day 1 and 8 hours after treatment, on day 1 of cycles 1 and 2.
干预措施: Correlative studies (Other)
结局指标
主要结局
Incidence of adverse events graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03
时间窗: 28 days
Types of toxicities, incidences and severity will be summarized by descriptive statistics such as frequencies/proportions.
次要结局
- CBR (complete response, partial response, stable disease or stable disease) using Response Evaluation Criteria in Solid Tumors(Up to 1 year)
- PFS(From date of registration to date of first documentation of progression or symptomatic deterioration or death due to any cause or last contact, assessed up to 1 year)
- Change in tumor markers by immunohistochemistry(Baseline to up to 1 year)
研究者
Kari Kendra
Principal Investigator
Ohio State University Comprehensive Cancer Center