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