Objective Evaluation of Paclitaxel/Docetaxel-induced Neuropathy in Breast Cancer Patients

The purpose of this prospective, non-interventional study is to perform neurological and cognitive assessment of breast cancer patients who receive standard of care single agent weekly paclitaxel docetaxel chemotherapy to determine the onset and severity of chemotherapy induced neuropathy (CIPN) and cognitive impairment (CICI).

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Chemotherapy Induced Peripheral Neuropathy; Paclitaxel Induced Neuropathy
• Intervention / Treatment: Diagnostic test: Quantitative measures of reduction in Chemotherapy Induced Neuropathy (CIPN) and Cognitive Impairment (CICI) in patients with stage I-III breast cancer

Detailed Description

The purpose of this prospective, non-interventional study is to perform neurological and cognitive assessment of breast cancer patients who receive standard of care single agent weekly paclitaxel or docetaxel chemotherapy to determine the onset and severity of chemotherapy induced neuropathy (CIPN) and cognitive impairment (CICI).

• Study Type: Observational
• Enrollment (Actual): 13

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Smilow Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Patients with Stage I-III breast cancer who will receive paclitaxel (80 mg/m2) or docetaxel (60-100mg/m2) as part of their standard of care adjuvant or neoadjuvant therapy are eligible for this study. Women of all races and ethnic groups will be eligible for this trial.

Description

Inclusion Criteria:

• Women ages 18 to 70 with histologically confirmed clinically stage I-III breast cancer who will receive weekly paclitaxel (80 mg/m2) or docetaxel (60-100mg/m2) chemotherapy as part of their routine care.

Exclusion Criteria:

• diabetes mellitus
• prior history of neuropathy or symptoms of numbness or peripheral pain, or prior neurotoxic chemotherapy.
• current symptoms of numbness and neuropathic pain
• treatment for bipolar disease
• treatment or concomitant use of common medications used to treat neuropathic pain, such as amitriptyline, gabapentin, pregabalin, duloxetine, for any indication
• limited English that would preclude understanding and completion of the study questionnaires
• pregnancy
• life expectancy <12 weeks
• participation in other research studies either concurrent with or within 30 days prior to participation in this study may be an exclusion criteria

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

patients with stage I-III breast cancer; Patients with Stage I-III breast cancer who will receive paclitaxel or docetaxel treatments as part of their standard of care adjuvant or neoadjuvant therapy are eligible for this study.

Diagnostic test: Quantitative measures of reduction in Chemotherapy Induced Neuropathy (CIPN) and Cognitive Impairment (CICI) in patients with stage I-III breast cancer; Quantitative measures that include additional aspects of peripheral neuropathy, such as pain, thermal allodynia, numbness and tingling are needed. We propose to evaluate several pharmacodynamics biomarkers in patients before and during chemotherapy: changes in nerve conduction velocity and amplitude, quantitative sensory testing (QST), computer based cognitive assessment, and rate of drop-out from treatment. The tests from this list that best correlate with decreased CIPN would be added to EORTC QLQ-CIPN20 scores and will provide an early indication of CIPN and/or CICI.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Verbal Memory Test	The phrase "Shopping List Learning" is displayed on screen. The pre-task on-screen instructions tell the test supervisor to start this task with the screen facing the supervisor so that the subject cannot see the screen. There are 3 initial rounds of this test. In the first round, the subject is told by the test supervisor: "In this task, I am going to read you a shopping list. I would like you to remember as many items from this list as possible.Total number of correct responses made in remembering the 16 word list on three consecutive learning trials. (Higher score = better performance)	20 minutes
Information processing psychomotor function	The pre-task on-screen instructions ask: "Has the card turned over?" The test supervisor reads the full instructions to the subject from the test supervisor script. To begin the task, a playing card is presented in the center of the screen. The card will flip over so it is face up. As soon as it does, the subject must press the "Yes" key. The card will go to the back of the pack and the subject must press the "Yes" key as soon as the next card flips over and so on. The subject will practice until they reach the required number of responses, or until the practice period expires. Then, on screen instructions for the real test are presented. The test supervisor or subject must press the "Enter" key to begin the real test. Speed of performance; mean of the log10 transformed reaction times for correct responses. Lower score = better performance	20 minutes
Identification	To begin the task, the test supervisor or subject must press the "Enter" key. A playing card is presented in the center of the screen. The card will flip over so it is face up. As soon as it does this the subject must decide whether the card is red or not. If it is red they should press "Yes", if it is not red they should press "No". The subject will practice until they reach the required number of responses, or until the practice period expires. Then, on screen instructions for the real test are presented. The subject should be encouraged to work as quickly as they can and be as accurate as they can. Low score = better performance.	20 minutes
Visual Working Memory	The pre-task on-screen instructions ask: "Is the previous card the same?" The test supervisor will read full instructions to the subject from the test supervisor script. To begin the task,a playing card is presented in the center of the screen. As soon as it does the subject must decide whether or not the card is the same as the previous one. As this is the first card in this task, the first answer is always "No". Each time a card is revealed, the subject must decide whether the card presented is the same as the one immediately presented previously, and respond by pressing the "Yes" or "No" key. The subject should be encouraged to work as quickly as they can and be as accurate as they can. Speed of performance; mean of the log10 transformed reaction times for correct responses. Lower score = better performance	20 minutes
Visual Learning Memory	The pre-task on-screen instructions ask: "Have you seen this card before in this task?" The test supervisor will read full instructions to the subject from the test supervisor script. To begin the task, the test supervisor or subject must press the "Enter" key. A playing card is presented in the center of the screen. As soon as it does the subject must decide whether or not the same card has been seen before in this task. Therefore, the first answer is always "No". Each time a card is revealed, the subject must decide whether they have been shown that card before in this task and respond by pressing the "Yes" or "No" key. The subject should be encouraged to work as quickly as they can and be as accurate as they can. Accuracy of performance; arcsine transformation of the proportion of correct responses. Higher score = better performance	20 minutes
Verbal Memory Test - Delay	The test supervisor presses the "ENTER" key to begin and instructs the subject "Tell me as many of the items on the shopping list that you learned earlier as you can remember now." They then note all of the items recalled by the subject by clicking/touching the corresponding button on screen with the stylus or mouse. Total number of correct responses made in recalling the 16 words learned previously after a delay. (Higher score = better performance	20 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To correlate neuronal calcium sensor 1 (NCS1) levels with development of chemotherapy-induced peripheral neuropathy (CIPN) and/or chemotherapy-induced cognitive impairment (CICI) in human patients.	Blood samples will be collected in heparinized tubes before the first paclitaxel/docetaxel treatment (baseline). We will collect approximately 20 mL of blood from each subject. White blood cells will be isolated using standard procedures. NCS1 levels will be assessed by Western blot analysis and by qPCR. Additional parameters will be monitored, especially if the variability in NCS1 levels is large. Parameters will be chosen from our understanding of the biochemical pathways identified in the Ehrlich laboratory as part of a separate on-going basic project. The prospective NCS1 values will be correlated with the assessment of CIPN and CICI in each patient obtained in Aim 1.	baseline
To correlate NCS1 levels with development of CIPN and/or CICI in human patients.	Blood samples will be collected in heparinized tubes before the first paclitaxel/docetaxel treatment and at week 6 during therapy. We will collect approximately 20 mL of blood from each subject. White blood cells will be isolated using standard procedures. NCS1 levels will be assessed by Western blot analysis and by qPCR. Additional parameters will be monitored, especially if the variability in NCS1 levels is large. Parameters will be chosen from our understanding of the biochemical pathways identified in the Ehrlich laboratory as part of a separate on-going basic project. The prospective NCS1 values will be correlated with the assessment of CIPN and CICI in each patient obtained in Aim 1.	6 weeks
To correlate NCS1 levels with development of CIPN and/or CICI in human patients.	Blood samples will be collected in heparinized tubes before the first paclitaxel/docetaxel treatment at week 12 during therapy. We will collect approximately 20 mL of blood from each subject. White blood cells will be isolated using standard procedures. NCS1 levels will be assessed by Western blot analysis and by qPCR. Additional parameters will be monitored, especially if the variability in NCS1 levels is large. Parameters will be chosen from our understanding of the biochemical pathways identified in the Ehrlich laboratory as part of a separate on-going basic project. The prospective NCS1 values will be correlated with the assessment of CIPN and CICI in each patient obtained in Aim 1.	12 weeks

Collaborators and Investigators

• Sponsor: Yale University
• Investigators: Principal Investigator: Barbara Ehrlich, PhD, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2017
• Primary Completion (Actual): February 25, 2021
• Study Completion (Actual): February 25, 2021

Study Registration Dates

• First Submitted: March 7, 2019
• First Submitted That Met QC Criteria: March 11, 2019
• First Posted (Actual): March 13, 2019

Study Record Updates

• Last Update Posted (Actual): May 3, 2021
• Last Update Submitted That Met QC Criteria: April 30, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: taxane; docetaxel; neuropathy
• Additional Relevant MeSH Terms: Nervous System Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Neuromuscular Diseases; Breast Neoplasms; Peripheral Nervous System Diseases
• Other Study ID Numbers: 2000020709

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No