Phase 2a Desipramine in Small Cell Lung Cancer and Other High-Grade Neuroendocrine Tumors
Condition: Small Cell Lung Cancer (SCLC); Neuroendocrine Tumors
MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma; Neuroendocrine Tumors
Intervention: Desipramine HCL
Intervention description: Desipramine is a tricyclic antidepressant (TCA). All patients will start off with a 25 mg dose by mouth nightly (QHS), increasing weekly for 6 weeks. The target dose level at 6 weeks is 450 mg (maximum dosage) or the maximum tolerated dose (MTD) for each subject.
Intervention MeSH terms: Desipramine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Intrapatient dose escalation study of desipramine in subjects with small cell lung cancer
      (SCLC) and other high-grade neuroendocrine tumors.
    

Eligibility criteria:

        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