Phase 2a Desipramine in Small Cell Lung Cancer and Other High-Grade Neuroendocrine Tumors

Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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