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A Phase IIa Intrapatient Dose Escalation Study of Desipramine in Small Cell Lung Cancer and Other High-Grade Neuroendocrine Tumors

Phase 2
18 Years
Open (Enrolling)
Small Cell Lung Cancer

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Trial Information

A Phase IIa Intrapatient Dose Escalation Study of Desipramine in Small Cell Lung Cancer and Other High-Grade Neuroendocrine Tumors

Primary Objective:

To determine the overall response rate (ORR) of small cell lung cancer and high-grade
neuroendocrine tumors in patients during treatment with desipramine.

Secondary Objectives:

- To determine the progression-free survival (PFS) and overall survival (OS).

- To perform exploratory blood biomarker analysis of PCSK1 and ROBO1 in patients enrolled
on this trial.

- To measure safety of desipramine using type, frequency and severity of adverse event
reactions reported according to CTCAE v4.0

- To measure tolerability using the incidence of adverse events (AEs) leading to
desipramine delay or discontinuation

- To establish the MTD of desipramine in each patient by adhering to an intrapatient dose
escalation schema

- To measure serum desipramine levels during treatment

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

- 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

- 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

- 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

- Ability to understand and the willingness to sign a written informed consent

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

- 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

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall Response Rate (ORR): Number of patients who achieve either a partial or complete response divided by the total number of patients treated on the study as measured by CT scans and RECIST 1.1 criteria.

Outcome Time Frame:

At baseline and every 8 weeks up to 3 years.

Safety Issue:


Principal Investigator

Joel Neal

Investigator Role:

Principal Investigator

Investigator Affiliation:

Stanford University


United States: Federal Government

Study ID:




Start Date:

October 2012

Completion Date:

Related Keywords:

  • Small Cell Lung Cancer
  • Lung Neoplasms
  • Small Cell Lung Carcinoma
  • Neuroendocrine Tumors



Stanford University Cancer InstituteStanford, California  94305