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

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ClinicalTrials.gov Identifier: NCT03872141
Recruitment Status : Recruiting
First Posted : March 13, 2019
Last Update Posted : September 26, 2019
Sponsor:
Information provided by (Responsible Party):
Yale University

Brief Summary:
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).

Condition or disease Intervention/treatment
Breast Cancer Chemotherapy Induced Peripheral Neuropathy Paclitaxel Induced Neuropathy 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).

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Study Type : Observational
Estimated Enrollment : 20 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Objective Evaluation of Paclitaxel/Docetaxel-induced Neuropathy in Breast Cancer Patients
Actual Study Start Date : May 23, 2017
Estimated Primary Completion Date : May 30, 2020
Estimated Study Completion Date : May 30, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

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.




Primary Outcome Measures :
  1. Verbal Memory Test [ Time Frame: 20 minutes ]
    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)

  2. Information processing psychomotor function [ Time Frame: 20 minutes ]

    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


  3. Identification [ Time Frame: 20 minutes ]

    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.


  4. Visual Working Memory [ Time Frame: 20 minutes ]

    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


  5. Visual Learning Memory [ Time Frame: 20 minutes ]

    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


  6. Verbal Memory Test - Delay [ Time Frame: 20 minutes ]

    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



Secondary Outcome Measures :
  1. 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. [ Time Frame: baseline ]
    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.

  2. To correlate NCS1 levels with development of CIPN and/or CICI in human patients. [ Time Frame: 6 weeks ]
    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.

  3. To correlate NCS1 levels with development of CIPN and/or CICI in human patients. [ Time Frame: 12 weeks ]
    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.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   women with histologically confirmed clinically stage I-III breast cancer
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.
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03872141


Contacts
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Contact: Eiman Ibrahim 203-737-1158 eiman.ibrahim@yale.edu

Locations
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United States, Connecticut
Smilow Cancer Center Recruiting
New Haven, Connecticut, United States, 06510
Contact: Lajos Pusztai, MD    203-737-7059    lajos.pusztai@yale.edu   
Sponsors and Collaborators
Yale University
Investigators
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Principal Investigator: Barbara Ehrlich, PhD Yale University

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Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT03872141     History of Changes
Other Study ID Numbers: 2000020709
First Posted: March 13, 2019    Key Record Dates
Last Update Posted: September 26, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Yale University:
neuropathy
taxane
docetaxel
Additional relevant MeSH terms:
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Breast Neoplasms
Peripheral Nervous System Diseases
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neuromuscular Diseases
Nervous System Diseases
Paclitaxel
Docetaxel
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action