Phase IIa Desipramine in Small Cell Lung Cancer and Other High-Grade Neuroendocrine Tumors
This study is currently recruiting participants.
Verified September 2013 by Stanford University
Information provided by (Responsible Party):
Joel Neal, Stanford University
First received: October 29, 2012
Last updated: September 18, 2013
Last verified: September 2013
Intrapatient dose escalation of desipramine. Start at 75 mg daily. Increase by 75 mg weekly to maximum of 450 mg daily. Taper desipramine upon disease progression, unacceptable toxicity or patient withdrawal from study.
Small Cell Lung Cancer
||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||A Phase IIa Intrapatient Dose Escalation Study of Desipramine in Small Cell Lung Cancer and Other High-Grade Neuroendocrine Tumors
Primary Outcome Measures:
- 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. [ Time Frame: At baseline and every 8 weeks up to 3 years. ] [ Designated as safety issue: No ]
| Estimated Enrollment:
| Study Start Date:
| Estimated Primary Completion Date:
||October 2014 (Final data collection date for primary outcome measure)
Experimental: Arm 1
To determine the overall response rate (ORR) of small cell lung cancer and high-grade neuroendocrine tumors in patients during treatment with desipramine.
- 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
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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 (HPF).
- 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 80).
- 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 normal
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 treatment.
- Ability to understand and the willingness to sign a written informed consent document.
Cardiac disorders including the following:
- 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
- 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01719861
|Stanford University Cancer Institute
|Stanford, California, United States, 94305 |
|Contact: Stanford Cancer Clinical Trials Office 650-498-7061 email@example.com |
|Principal Investigator: Joel Neal |
No publications provided
||Joel Neal, Assistant Professor, Stanford University
History of Changes
|Other Study ID Numbers:
|Study First Received:
||October 29, 2012
||September 18, 2013
||United States: Federal Government
United States: Food and Drug Administration
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on December 09, 2013
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Molecular Mechanisms of Pharmacological Action
Antidepressive Agents, Tricyclic
Central Nervous System Agents
Adrenergic Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Physiological Effects of Drugs