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

NCT ID: NCT02881125

Last Updated: 2019-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

2 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-11-03

Study Completion Date

2019-11-30

Brief Summary

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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

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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.

Conditions

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Small Cell Carcinoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Nortriptyline Hydrochloride

Intervention Type DRUG

Given PO

Paclitaxel

Intervention Type DRUG

Given IV

Interventions

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Nortriptyline Hydrochloride

Given PO

Intervention Type DRUG

Paclitaxel

Given IV

Intervention Type DRUG

Other Intervention Names

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Allegron Norpress Pamelor Anzatax Asotax Bristaxol Praxel Taxol Taxol Konzentrat

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

University of Washington

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Robert Montgomery

Role: PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Locations

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Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2016-01197

Identifier Type: REGISTRY

Identifier Source: secondary_id

9618

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA015704

Identifier Type: NIH

Identifier Source: secondary_id

View Link

9618

Identifier Type: -

Identifier Source: org_study_id