Overview

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

Status:
Terminated
Trial end date:
2015-05-01
Target enrollment:
0
Participant gender:
All
Summary
Intrapatient dose escalation study of desipramine in subjects with small cell lung cancer (SCLC) and other high-grade neuroendocrine tumors.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Joel Neal
Treatments:
Desipramine
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