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

Inclusion Criteria:

• Metastatic small-cell lung cancer -or- 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. After progression on first-line chemotherapy, disease does not have to have progressed on subsequent lines of therapy to enroll on trial.

• Completed previous treatment in greater than or equal to the following times prior to initiation of study treatment:

  • Chemotherapy administered in a daily schedule must be completed >= 2 weeks prior to registration;
  • Chemotherapy administered in a weekly schedule must be completed >= 2 weeks prior to registration;
  • Chemotherapy administered in a 2-weekly schedule must be completed >= 3 weeks prior to registration;
  • Chemotherapy administered in a 3-weekly schedule must be completed >= 4 weeks prior to registration.
• ECOG Performance Status 0-2
• Measurable disease by RECIST 1.1 criteria
• Age at least 18 years-old otherwise no age, gender/race-ethnic restrictions
• At least 3 months estimated life expectancy.

• Laboratory tests within the following parameters:

  • Absolute neutrophil count >= 1,500/ mm3
  • Platelets >= 100,000/mm3
  • Hemoglobin >= 9 g/Dl
  • Total bilirubin <= 1.5 mg/dL
  • AST(SGOT) and ALT(SGPT) <= 3 X ULN (Stanford: AST(SGOT) ULN 60, ALT (SGPT) ULN 80).
  • Creatinine <=1.5 X ULN (Stanford: ULN 1.1) -or- Calculated (See Appendix F for Cockgroft-Gault formula) measured creatinine clearance >= 45 mL/min/1.73m2 (normalized to BSA) for patients with creatinine levels above institutional normal

• ECG demonstrating all of the following:

  • QT interval corrected using Fridericia's method (QTcF) <450 msec (males) or <470 msec (females) (see Appendix E for Fredericia's criteria).
  • PR <240 msec
  • QRS <100 msec
• Brain metastases are allowed, but 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:

• Cardiac disorders including the following:

  • 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
• Family history of long QT syndrome.
• Concomitant or expected treatment with any of the following prohibited study medications. Any prohibited drugs must be discontinued at least 2 weeks or 5-half lives prior to the initiation of desipramine, whichever is shortest (except fluoxetine, because of long half life, will need a at least a 5 week washout period). (see appendix C and D for lists of prohibited drugs)
• Medications that prolong the QT interval and are known to increase risk of torsades de pointes (see appendix D for excluded drugs)
• Strong inhibitors of cytochrome p450 CYP2D6 (see appendix C)
• Other anti-depressant or anti-psychotic including a SSRI, other tricyclic, MAOI, SNRI, 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

• Any of the following known psychiatric conditions, diagnosed by a psychiatrist, either ongoing or active within the last 5 years:

  • Bipolar disorder
  • Suicidal ideation
  • Suicide attempt
• Patients who are pregnant or breastfeeding. Female subjects of childbearing potential must have a negative pregnancy test prior to enrollment and practice acceptable methods of birth control to avoid pregnancy. Male subjects must also practice acceptable methods of birth control to prevent pregnancy of a partner.
• No other Investigational Agents allowed while on this trial.
• Any other serious or unstable concomitant systemic disorder that in the opinion of the investigator is incompatible with the clinical study