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

NCT01719861 | Terminated Phase 2 Results DMC

• 2 other identifiers: IRB-25491VAR0087
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Small Cell Lung Cancer (SCLC); Neuroendocrine Tumors

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  Overall response rate (ORR) was assessed as the number of patients who achieve either a partial (PR) or complete response (CR) measured by CT scans and Response Evaluation Criteria In Solid Tumors (RECIST 1.1) criteria, divided by the total number of patients treated on the study. CR: Disappearance of all target lesions, all non-target lesions, and no new lesion. PR: At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesion.

  6 weeks

Secondary Outcomes (4)

• Desipramine Maximum Dose

  Up to 6 weeks

• Median Serum Desipramine Levels During Treatment

  Up to 6 weeks

• Progression-free Survival (PFS), Median

  Up to 5 years from enrollment to radiographic progression or drug discontinuation

• Median Overall Survival (OS)

  From start of enrollment until death, no limit

Study Arms (1)

Desipramine HCl

EXPERIMENTAL

Desipramine is a tricyclic antidepressant (TCA).

Drug: Desipramine HCL

Interventions

Desipramine HCL DRUG

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.

Also known as: Norpramin, Pertofrane, Desmethylimipramine

Desipramine HCl

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Joel Neal: lead

Study Sites (1)

Stanford University Cancer Institute

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma; Neuroendocrine Tumors

Interventions

Desipramine

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

This study had to be terminated early because patients with small cell lung cancer were not able to tolerate clinically relevant doses of desipramine, and no clinical activity was observed in the first enrolled patients.

Results Point of Contact

• Title: Joel Neal, MD, PhD; Assistant Professor of Medicine
• Organization: Stanford University Medical Center

jwneal@stanford.edu

650-725-3081

Study Officials

• Joel W Neal, MD, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: October 29, 2012
• First Posted: November 1, 2012
• Study Start: October 1, 2012
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2015
• Last Updated: April 17, 2017
• Results First Posted: April 17, 2017

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)