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

Sponsor

University of Washington (Other)

Overall Status

Completed

CT.gov ID

NCT02881125

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

36.9

Actual Duration (Months)

0.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Small Cell Carcinoma	Drug: Nortriptyline Hydrochloride Drug: Paclitaxel	Phase 1

Detailed Description

PRIMARY OBJECTIVES:

To determine the maximally tolerated dose (MTD) of nortriptyline hydrochloride (nortriptyline) combined with weekly paclitaxel (PC).

SECONDARY OBJECTIVES:

To assess the overall response rate (ORR) to nortriptyline combined with PC.
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 Design

Study Type:

Interventional

Actual Enrollment :

2 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1 Study of Weekly Paclitaxel and Nortriptyline for Relapsed Small Cell Carcinoma

Actual Study Start Date :

Nov 3, 2016

Actual Primary Completion Date :

Jan 1, 2018

Actual Study Completion Date :

Nov 30, 2019

Arms and Interventions

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.	Drug: Nortriptyline Hydrochloride Given PO Other Names: Allegron Norpress Pamelor Drug: Paclitaxel Given IV Other Names: Anzatax Asotax Bristaxol Praxel Taxol Taxol Konzentrat

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.

Drug: Nortriptyline Hydrochloride

Given PO

Other Names:

Allegron

Norpress

Pamelor

Drug: Paclitaxel

Given IV

Other Names:

Anzatax

Asotax

Bristaxol

Praxel

Taxol

Taxol Konzentrat

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Objective tumor response evaluated according to Response Evaluation Criteria in Solid Tumors version 1.1 [Up to 2 years]
Objective tumor response will be assessed with a 95% confidence interval.
Overall Survival [Up to 2 years]
Overall Survival will be described using Kaplan-Meier curves.
Progression free survival [Up to 2 years]
Progression free survival will be described using Kaplan-Meier curves.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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