A Phase 2a Intrapatient Dose Escalation Study of Desipramine in Small Cell Lung Cancer and Other High-Grade Neuroendocrine Tumors
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
Intrapatient dose escalation study of desipramine in subjects with small cell lung cancer (SCLC) and other high-grade neuroendocrine tumors.
详细描述
Participants will start desipramine by mouth nightly (QHS) for 6 weeks, with weekly dose escalation. Starting dose will be 25 to 75 mg. The desipramine dose will be escalated until the maximum dose of 450 mg is reached or a maximum safe dose per subject is established.
Dose level may be adjusted (decreased) based on cardiac or general adverse effects. desipramine level will be tapered if the subject experience disease progression, unless physician judges immediate suspension is in the subjects best interest.
Assessments will be conducted every 28 days, and will include ECGs, physicians and blood samples.
One partial and/or complete response will be sufficient to consider a larger clinical trial.
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
- •Metastatic small-cell lung cancer
- •Metastatic high-grade neuroendocrine carcinoma of any organ system (high-grade defined by Ki-67 ≥ 20% and/or ≥ 20 mitoses/10 (HPF).
- •Received at least one line of prior chemotherapy treatment for metastatic disease.
- •Daily chemotherapy must be completed ≥ 2 weeks prior to registration
- •Weekly chemotherapy must be completed ≥ 2 weeks prior to registration
- •Chemotherapy every 2 weeks must be completed ≥ 3 weeks prior to registration
- •Chemotherapy every 3 weeks must be completed ≥ 4 weeks prior to registration
- •ECOG Performance Status 0 to 2
- •Measurable disease by RECIST 1.1 criteria
- •Age at least 18 years
- •Estimated life expectancy at least 3 months
- •Absolute neutrophil count ≥ 1,500/ mm³
- •Platelets ≥ 100,000/mm³
- •Hemoglobin ≥ 9 g/dL
- •Total bilirubin ≤ 1.5 mg/dL, OR ≤ 2 X ULN if tumor involves the liver
- •AST(SGOT)
- •ALT(SGPT) ≤ 3 X ULN
- •Creatinine ≤ 1.5 X ULN
- •Creatinine clearance ≥ 45 mL/min/1.73m²) for patients with creatinine levels above institutional normal
- •QT interval corrected using Fridericia's method (QTcF) < 450 msec (males) or < 470 msec (females)
- •PR < 240 msec
- •QRS < 100 msec
- •Brain metastases must be asymptomatic and have been adequately treated with radiation finishing at least 1 week prior to initiation of study treatment.
- •Ability to understand and the willingness to sign a written informed consent document.
排除标准
- •Clinically-significant ventricular arrhythmia including cardiac arrest
- •Myocardial infarction from coronary artery disease within 3 months of study enrollment
- •Implantable pacemaker or implantable cardioverter defibrillator
- •NYHA Class III or greater congestive heart failure
- •Other clinically-significant cardiac disorders
- •Family history of long QT syndrome.
- •Concomitant or expected treatment with strong inhibitors of cytochrome p450 CYP2D6, specifically including Bupropion; Fluoxetine; or Paroxetine (must be discontinued at least 2 weeks or 5-half lives prior to the initiation of desipramine, whichever is shortest, except fluoxetine which requires at least a 5-week washout period).
- •Use of medications known to increase risk of torsades de pointes, including Amiodarone; Arsenic trioxide; Astemizole; Azithromycin; Bepridil; Chloroquine; Chlorpromazine; Cisapride; Citalopram; Clarithromycin; Disopyramide; Dofetilide; Domperidone; Droperidol; Erythromycin; Flecainide; Halofantrine; Haloperidol; Ibutilide; Levomethadyl; Mesoridazine; Methadone; Moxifloxacin; Pentamidine; Pimozide; Probucol; Procainamide; Quinidine; Sotalol; Sparfloxacin; Terfenadine; Thioridazine; Vandetanib
- •Other anti-depressant or anti-psychotic medications including selective serotonin re-uptake inhibitors (SSRIs); other tricyclic, monoamine oxidase inhibitors (MAOIs); serotonin-norepinephrine reuptake inhibitors (SNRIs, typical or atypical anti-psychotic)
- •Metoclopramide (Reglan) because of increased risk of extrapyrimidal symptoms and neuroleptic malignant syndrome
- •Symptomatic orthostatic hypotension despite adequate volume resuscitation.
- •Medical history of narrow angle glaucoma
- •Bipolar disorder, ongoing or active within the last 5 years
- •Suicidal ideation, ongoing or active within the last 5 years
- •Suicide attempt, ongoing or active within the last 5 years
- •Pregnancy
- •Breastfeeding
- •Receiving any other investigational agents
- •Any other serious or unstable concomitant systemic disorder that in the opinion of the investigator is incompatible with the clinical study
研究组 & 干预措施
Desipramine HCl
Desipramine is a tricyclic antidepressant (TCA).
干预措施: Desipramine HCL (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: 6 weeks
Overall response rate (ORR) was assessed as the number of patients who achieve either a partial (PR) or complete response (CR) measured by CT scans and Response Evaluation Criteria In Solid Tumors (RECIST 1.1) criteria, divided by the total number of patients treated on the study. CR: Disappearance of all target lesions, all non-target lesions, and no new lesion. PR: At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesion.
次要结局
- Median Serum Desipramine Levels During Treatment(Up to 6 weeks)
- Desipramine Maximum Dose(Up to 6 weeks)
- Progression-free Survival (PFS), Median(Up to 5 years from enrollment to radiographic progression or drug discontinuation)
- Median Overall Survival (OS)(From start of enrollment until death, no limit)
研究者
Joel Neal
Assistant Professor
Stanford University