Phase 2a Desipramine in Small Cell Lung Cancer and Other High-Grade Neuroendocrine Tumors
|Small Cell Lung Cancer (SCLC) Neuroendocrine Tumors||Drug: Desipramine HCL||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase 2a Intrapatient Dose Escalation Study of Desipramine in Small Cell Lung Cancer and Other High-Grade Neuroendocrine Tumors|
- Overall Response Rate (ORR) [ Time Frame: 6 weeks ]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.
- Desipramine Maximum Dose [ Time Frame: Up to 6 weeks ]Assessed as the median per patient maximum dose (MD) using intra-patient dose escalation, and reported as the highest dose of desipramine administered continuously for 1 week or greater.
- Median Serum Desipramine Levels During Treatment [ Time Frame: Up to 6 weeks ]
Median serum desipramine levels during treatment is reported as the median of the maximum steady state serum concentration observed in all patients.
Therapeutic concentration of desipramine is 100 to 300 ng/mL, and toxic concentration is > 300 ng/mL.
- Progression-free Survival (PFS), Median [ Time Frame: Up to 5 years from enrollment to radiographic progression or drug discontinuation ]Median PFS was defined as the time from randomization to disease progression (or death if the patient died before progression) calculated using the Kaplan-Meier method.
- Median Overall Survival (OS) [ Time Frame: From start of enrollment until death, no limit ]Median overall survival was defined as time from enrollment to death from any cause calculated using the Kaplan-Meier method.
|Study Start Date:||October 2012|
|Study Completion Date:||May 2015|
|Primary Completion Date:||May 2014 (Final data collection date for primary outcome measure)|
Experimental: Desipramine HCl
Desipramine is a tricyclic antidepressant (TCA).
Drug: Desipramine HCL
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.
Participants will start desipramine by mouth nightly (QHS) for 6 weeks, with weekly dose escalation. Starting dose will be 25 to 75 mg. The desipramine dose will be escalated until the maximum dose of 450 mg is reached or a maximum safe dose per subject is established.
Dose level may be adjusted (decreased) based on cardiac or general adverse effects. desipramine level will be tapered if the subject experience disease progression, unless physician judges immediate suspension is in the subjects best interest.
Assessments will be conducted every 28 days, and will include ECGs, physicians and blood samples.
One partial and/or complete response will be sufficient to consider a larger clinical trial.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01719861
|United States, California|
|Stanford University Cancer Institute|
|Stanford, California, United States, 94305|
|Principal Investigator:||Joel W Neal, MD, PhD||Stanford University|