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