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