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Paclitaxel and Nortriptyline Hydrochloride in Treating Patients With Relapsed Small Cell Carcinoma

Primary Purpose

Small Cell Carcinoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Nortriptyline Hydrochloride
Paclitaxel
Sponsored by
University of Washington
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Small Cell Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Fred Hutch/University of Washington Cancer Consortium

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (paclitaxel, nortriptyline hydrochloride)

Arm Description

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.

Outcomes

Primary Outcome Measures

Maximum tolerated dose, determined by the number of patients who experience a dose limiting toxicity
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.

Secondary Outcome Measures

Objective tumor response evaluated according to Response Evaluation Criteria in Solid Tumors version 1.1
Objective tumor response will be assessed with a 95% confidence interval.
Overall Survival
Overall Survival will be described using Kaplan-Meier curves.
Progression free survival
Progression free survival will be described using Kaplan-Meier curves.

Full Information

First Posted
August 23, 2016
Last Updated
December 16, 2019
Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT02881125
Brief Title
Paclitaxel and Nortriptyline Hydrochloride in Treating Patients With Relapsed Small Cell Carcinoma
Official Title
A Phase 1 Study of Weekly Paclitaxel and Nortriptyline for Relapsed Small Cell Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
December 2019
Overall Recruitment Status
Completed
Study Start Date
November 3, 2016 (Actual)
Primary Completion Date
January 1, 2018 (Actual)
Study Completion Date
November 30, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This phase I trial studies the side effects and best dose of nortriptyline hydrochloride when given together with paclitaxel in treating patients with small cell carcinoma that has come back. Nortriptyline hydrochloride, may help disrupt survival signals and cause cancer cell death. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving nortriptyline hydrochloride and paclitaxel may work better in treating patients with small cell carcinoma.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Small Cell Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (paclitaxel, nortriptyline hydrochloride)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Nortriptyline Hydrochloride
Other Intervention Name(s)
Allegron, Norpress, Pamelor
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Other Intervention Name(s)
Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Maximum tolerated dose, determined by the number of patients who experience a dose limiting toxicity
Description
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.
Time Frame
Up to 28 days
Secondary Outcome Measure Information:
Title
Objective tumor response evaluated according to Response Evaluation Criteria in Solid Tumors version 1.1
Description
Objective tumor response will be assessed with a 95% confidence interval.
Time Frame
Up to 2 years
Title
Overall Survival
Description
Overall Survival will be described using Kaplan-Meier curves.
Time Frame
Up to 2 years
Title
Progression free survival
Description
Progression free survival will be described using Kaplan-Meier curves.
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Montgomery
Organizational Affiliation
Fred Hutch/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutch/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

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Paclitaxel and Nortriptyline Hydrochloride in Treating Patients With Relapsed Small Cell Carcinoma

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