- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02881125
Paclitaxel and Nortriptyline Hydrochloride in Treating Patients With Relapsed Small Cell Carcinoma
A Phase 1 Study of Weekly Paclitaxel and Nortriptyline for Relapsed Small Cell Carcinoma
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the maximally tolerated dose (MTD) of nortriptyline hydrochloride (nortriptyline) combined with weekly paclitaxel (PC).
SECONDARY OBJECTIVES:
I. To assess the overall response rate (ORR) to nortriptyline combined with PC.
II. To assess progression free survival (PFS) and overall survival (OS).
OUTLINE: This is a dose-escalation study of nortriptyline hydrochloride.
Patients receive paclitaxel intravenously (IV) on days 1, 8, and 15. Patients also receive nortriptyline hydrochloride orally (PO) once daily (QD) on days 1-7, twice daily (BID) on days 8-14, and thrice daily (TID) on days 15-28 of course 1 and TID on days 1-28 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 28 days and every 3 months for 2 years.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Washington
-
Seattle, Washington, United States, 98109
- Fred Hutch/University of Washington Cancer Consortium
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Ability to understand and the willingness to sign a written informed consent
- Pathologically-confirmed small cell carcinoma of any primary site
- Relapse following platinum-based chemotherapy or documented progressive disease while on platinum-based chemotherapy
- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 at time of informed consent
- Absolute neutrophil count >= 1.5 x 10^9 cells/L
- Hemoglobin (Hgb) >= 9.0 g/dL
- Platelets >= 100,000 x 10^9/L
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)
- Alkaline phosphatase levels =< 2.5 x upper limit of normal (ULN)
- Total bilirubin =< 1.5 x ULN
- Serum creatinine < 1.5 mg/dL
- At least one site of measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria on computed tomography (CT) scan done within 30 days prior to study start
- Women of child-bearing potential and sexually active men must agree to use adequate contraception (hormonal, barrier method, or abstinence) prior to study entry, during treatment, and for three months after completing treatment
- Baseline electrocardiogram demonstrating all of the following: corrected QT (QTc) < 450 milliseconds (msec) (men) and < 470 msec (women), PR < 240 msec, QRS < 100 msec
Exclusion Criteria:
- Untreated active major depression
- Bipolar disorder
- Pregnancy and lactation; refusal to use adequate contraception
- History of seizures in the past 3 years
- Concurrent therapy with monoamine oxidase inhibitors (MAOI), selective serotonin reuptake inhibitors (SSRI), or other tricyclic antidepressants (TCA) or use within 2 weeks study start
- Concomitant therapy with any drugs shown to have major interactions with nortriptyline (i.e. known inhibitors of cytochrome P450 family 2 subfamily D member 6 [CYP2D6]) and use during the 30-day period prior to study start
- Myocardial infarction in preceding 4 weeks; history of uncontrolled cardiac arrhythmias or family history of sudden cardiac death
- Peripheral neuropathy grade 2 or greater
- Progressive or symptomatic central nervous system (CNS) metastases; patients with known brain metastasis must have stable disease following treatment surgery, radiation, or both
- Glaucoma
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (paclitaxel, nortriptyline hydrochloride)
Patients receive paclitaxel IV on days 1, 8, and 15.
Patients also receive nortriptyline hydrochloride PO QD on days 1-7, BID on days 8-14, and TID on days 15-28 of course 1 and TID on days 1-28 of subsequent courses.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
|
Given IV
Other Names:
Given PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum tolerated dose, determined by the number of patients who experience a dose limiting toxicity
Time Frame: Up to 28 days
|
Maximum tolerated dose defined as the highest dose level of nortriptyline (in combination with weekly paclitaxel) where < 1/3 or < 2/6 patients experience a dose-limiting toxicity evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
|
Up to 28 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective tumor response evaluated according to Response Evaluation Criteria in Solid Tumors version 1.1
Time Frame: Up to 2 years
|
Objective tumor response will be assessed with a 95% confidence interval.
|
Up to 2 years
|
Overall Survival
Time Frame: Up to 2 years
|
Overall Survival will be described using Kaplan-Meier curves.
|
Up to 2 years
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Progression free survival
Time Frame: Up to 2 years
|
Progression free survival will be described using Kaplan-Meier curves.
|
Up to 2 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Robert Montgomery, Fred Hutch/University of Washington Cancer Consortium
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Lung Neoplasms
- Carcinoma
- Small Cell Lung Carcinoma
- Carcinoma, Small Cell
- Physiological Effects of Drugs
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Psychotropic Drugs
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Antidepressive Agents
- Antidepressive Agents, Tricyclic
- Adrenergic Uptake Inhibitors
- Paclitaxel
- Albumin-Bound Paclitaxel
- Nortriptyline
Other Study ID Numbers
- 9618 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)
- P30CA015704 (U.S. NIH Grant/Contract)
- NCI-2016-01197 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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