NCT02881125

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
2

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Nov 2016

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 23, 2016

Completed
3 days until next milestone

First Posted

Study publicly available on registry

August 26, 2016

Completed
2 months until next milestone

Study Start

First participant enrolled

November 3, 2016

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2018

Completed
1.9 years until next milestone

Study Completion

Last participant's last visit for all outcomes

November 30, 2019

Completed
Last Updated

December 17, 2019

Status Verified

December 1, 2019

Enrollment Period

1.2 years

First QC Date

August 23, 2016

Last Update Submit

December 16, 2019

Conditions

Outcome Measures

Primary Outcomes (1)

  • 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.

    Up to 28 days

Secondary Outcomes (3)

  • Objective tumor response evaluated according to Response Evaluation Criteria in Solid Tumors version 1.1

    Up to 2 years

  • Overall Survival

    Up to 2 years

  • Progression free survival

    Up to 2 years

Study Arms (1)

Treatment (paclitaxel, nortriptyline hydrochloride)

EXPERIMENTAL

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 HydrochlorideDrug: Paclitaxel

Interventions

Given PO

Also known as: Allegron, Norpress, Pamelor
Treatment (paclitaxel, nortriptyline hydrochloride)

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat
Treatment (paclitaxel, nortriptyline hydrochloride)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Carcinoma, Small Cell

Interventions

NortriptylinePaclitaxelTaxes

Condition Hierarchy (Ancestors)

CarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasms

Intervention Hierarchy (Ancestors)

DibenzocycloheptenesBenzocycloheptenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic CompoundsTaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicDiterpenesTerpenesEconomicsHealth Care Economics and Organizations

Study Officials

  • Robert Montgomery

    Fred Hutch/University of Washington Cancer Consortium

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 23, 2016

First Posted

August 26, 2016

Study Start

November 3, 2016

Primary Completion

January 1, 2018

Study Completion

November 30, 2019

Last Updated

December 17, 2019

Record last verified: 2019-12

Locations