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Completed

NCT Number: NCT02549534

Early Detection of Taxane-Induced Neuropathy in Women With Breast Cancer

Purpose: The purpose of the study is to test a new way of measuring nerve damage in women with breast cancer receiving chemotherapy drug paclitaxel (Taxol).

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Key information

Conditions

Peripheral Neuropathy Breast Diseases Breast Neoplasms Neoplasms Neoplasms by Site Nervous System Diseases Neuromuscular Diseases Peripheral Nervous System Diseases Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year–85 year

Sex eligibility

Female

Study type

Observational

Primary location

Indiana University Melvin and Bren Simon Cancer Center (IUSCC), Indianapolis, Indiana, United States

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About this study

Purpose: The study has four aims;

  • The primary aim of the study is to determine whether women who are receiving either weekly Taxol (80-100 mg/m2) or bi-weekly Taxol (i.e.,dose-dense; 175 mg/m2) show deficits in axon-reflex mediated vasodilation (AMV) over the course of six weeks of Taxol therapy similar to those that have been reported in patients with diabetic and genetically-inherited neuropathies.
  • The second aim of the study is to determine whether women who are receiving either weekly or dose-dense Taxol develop changes in AMV before developing signs & symptoms of chemotherapy-induced peripheral neuropathy (CIPN) in a way that supports using changes in AMV as an early detection method for small-fiber CIPN.
  • A third (exploratory) aim of the study is to determine whether any changes in AMV detected during the study are significantly correlated with self-reported CIPN in a way that would support using changes in AMV as a confirmatory marker for CIPN.
  • A final (exploratory) aim of the study is to describe the size of axon reflexes and axon flares in women receiving weekly Taxol before they start their pre-Taxol anthracycline & cyclophosphamide (AC) therapy.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

for Women with Breast Cancer:

  • Age 18-85
  • Able to read, write, and understand English
  • Diagnosed with histologically-confirmed, first-time, non-metastatic breast cancer (stage I-IIIB)
  • No prior exposure to neurotoxic chemotherapy or radiation at the time of enrollment,
  • Will be receiving weekly paclitaxel (Taxol® or generic paclitaxel, 80- 100mg/m2) or bi-weekly Taxol (i.e., dose-dense; 175 mg/m2) as a part of their cancer treatment regimen OR
  • Will be receiving an anthracycline and cyclophosphamide (AC) followed by weekly paclitaxel (Taxol® or generic paclitaxel, 80-100mg/m2) or bi-weekly Taxol (i.e., dose-dense; 175 mg/m2) as a part of their cancer treatment regimen;

Inclusion criteria

for Healthy Controls:

  • Aged 18-85
  • Can read, write, and understand English

Exclusion criteria

  • A history of cardiovascular disease, hypertension, or peripheral arterial/vascular disease;
  • Current use of (1) medications/supplements to control blood pressure (e.g. beta-blockers, nitrates, calcium channel blockers, Phosphodiesterase-5 (PGE5) inhibitors) or (2) the use of statins for cholesterol;
  • Suspected or diagnosed diabetes (with the exception of gestational diabetes);
  • Pre-existing neuropathy, neuropathic pain, or nerve injury;
  • Pain or significant arthritis in the toes of either foot;
  • Current skin disease or fungal infection of the feet;
  • Significant damage or deformity to the feet that would alter blood flow or make it impossible to measure/interpret findings;
  • Diagnosed or suspected vasospastic disease such as Raynaud's syndrome;
  • Current use of tobacco/tobacco-containing products;
  • Diagnosis of restless leg syndrome or other movement disorders that would prevent accurate data from being able to be collected.

In-Study Restrictions:

  • No caffeine- or alcohol-containing products for 12 hours prior to their study visit;
  • No food for at least one hour prior to blood flow monitoring;
  • No non-steroidal anti-inflammatory drugs (NSAIDS) for 24 hours prior to study visits unless directed by a physician to do so.

(Note: These restrictions are designed to improve the rigor and quality of the data, but non-compliance will not be grounds for study exclusion; adherence to these restrictions will be monitored during self-report).

Treatment and study plan

Axon Reflexes

Procedure

*Axon reflexes will be evoked in the palmar surface of the right great toe using local skin heating with a 0.33 cm2 heat probe using the following protocol:

  • Baseline: Heating the skin of the toe for a minimum of 5 minutes at 33*C.
  • Heat Ramp: Increasing the heat in the heat probe to 42*C at approx. 0.1*C/10 sec.
  • Skin Heating: Heating the skin of the toe for 30 minutes 42*C.
  • Heat Ramp: Increasing the heat in the heat probe to 44*C at 0.1*C/10 sec..
  • Skin Heating: Heating the skin for an additional 5 minutes at 44*C.

The size of the axon reflex during this skin heating protocol will be imaged using Laser Doppler Flowmetry (LDF). In the case that participants develop CIPN on their left side only, the left toe will be substituted.

Axon Flares

Procedure

Axon flares will be generated on the palmar surface of the right great toe using the same local skin heating protocol described above, and imaged using a laser speckle contrast imager (LSCI) (also known as full-field laser perfusion imager, or FLPI).

Other names: LDIflare, Heat-Evoked Axon Flare

Self-Reported Signs & Symptoms of CIPN

Procedure

Self-reported signs & symptoms of CIPN such as the presence and location of (1) tingling, (2) numbness, and (3) neuropathic pain, along with information about (4) deficits in vibration thresholds, and (5) loss of deep tendon reflexes will be assessed at each study visit using the 5-item, modified Total Neuropathy Score (mTNS).

Primary outcomes

  1. Differences in the mean size of axon reflexes between healthy women and women with breast cancer BEFORE starting Taxol.

    Time frame: Day 1 (before participant's 1st Taxol infusion).

    • Hypothesis: (Cross-Sectional): There WILL NOT be a significant difference in the mean size of axon reflexes (expressed as a %CVCmax) in the great toe between healthy women and women with breast cancer before they start Taxol (i.e., Day 1).
    • Definitions/Notes: The mean size of axon reflexes will be determined by averaging the peak laser doppler values (in tissue perfusion units (TPUs)) that occur during a stable 30-90 second period after increasing the probe temperature to 42*C. The maximum circulatory vascular conductance (%CVCmax) for each participant will be determined by dividing the raw TPU values by the participant's mean arterial blood pressure (MAP) during the axon reflex. The size of axon reflexes for each group will be then calculated by averaging the %CVCmax values corresponding to each individual's axon reflex for each group at that time point. Differences between groups in the size of axon reflexes at Day 1 will be compared using two-tailed t-tests, α=0.05.

  2. Differences in the mean size of axon reflexes between healthy women and women with breast cancer DURING Taxol therapy.

    Time frame: Day 14 (week two of Taxol therapy) and Day 42 (week six of Taxol therapy).

    • Hypothesis (Cross-Sectional): There WILL be a significant difference in the mean size of axon reflexes generated on the palmar surface of the right great toe between healthy controls and women with breast cancer during their initial six weeks of Taxol therapy (i.e., day 14 and 42, respectively).
    • Notes: The mean size of axon reflexes during Taxol therapy will be determined by averaging the size of axon reflexes for participants in each group at day 14 and 42, respectively. Differences between groups in the size of axon reflexes at day 14 and 42 will be compared using two-tailed t-tests, α=0.05.

  3. Differences in the mean size of axon reflexes OVER TIME for women with breast during the initial six weeks of Taxol therapy.

    Time frame: Day 1 (before participant's 1st Taxol infusion), day 14 (week two of Taxol therapy) and day 42 (week six of Taxol therapy).

    • Hypothesis (Longitudinal): There WILL be a significant difference in the mean size of axon reflexes generated on the palmar surface of the great toe of women with breast cancer from (a) day 1 to day 14, (b) day 14 to day 42, and from (c) day 1 to day 42.
    • Note: Differences in mean size of axon reflexes over the course of Taxol therapy will be calculated using repeated-measures analysis of covariance (RM-ANCOVA).

  4. Differences in the mean size of axon reflexes between healthy female controls OVER TIME the six-week study period.

    Time frame: Day 1 (before participant's 1st Taxol infusion), Day 14 (week two of Taxol therapy) and Day 42 (week six of Taxol therapy).

    • Hypothesis (Longitudinal): There WILL NOT be a significant difference in the size of axon reflexes on the palmar surface of the great toe of healthy female controls from(a) day 1 to day 14, (b) day 14 to day 42, and from (c) day 1 to day 42.
    • Note: Differences in mean size of axon reflexes over the course of Taxol therapy will be calculated using repeated-measures analysis of covariance (RM-ANCOVA).

Secondary outcomes

  1. Differences in the mean size of heat-evoked axon flares between healthy women and women with breast cancer BEFORE starting Taxol therapy.

    Time frame: Day 1 (before participant's 1st Taxol infusion).

    • Hypothesis (Cross-Sectional): There WILL NOT be a significant difference in the mean size of heat-evoked axon flares generated on the palmar surface of the great toe between healthy women and women with breast cancer before starting Taxol therapy (day 1).
    • Note: A "heat-evoked axon flare" is defined as the area of increased cutaneous blood flow surrounding heat probe that is at least three standard deviations (3SD) above blood flow measured during prior to local skin heating. The size of each axon flare will be expressed in centimeters squared (cm2). The mean size of axon flares for each group will be calculated by averaging the size of axon flares for healthy women at baseline and the size of axon flares for women with breast cancer at day 1 (before starting Taxol). Differences in the mean size of axon flares between both groups at day 1 will be compared using two-tailed t-tests, α=0.05.

  2. Differences in the mean size of heat-evoked axon flares between healthy women and women with breast cancer DURING six weeks of study visits.

    Time frame: Day 14 (week two of Taxol therapy) and Day 42 (week six of Taxol therapy).

    • Hypothesis (Cross-Sectional): There WILL be a significant difference in the mean size of heat-evoked axon flares generated on the palmar surface of the great toe between healthy controls and women with breast cancer DURING Taxol therapy at day 14 and 42 (respectively).
    • Note: Differences in the size of heat-evoked axon flares between healthy women and women with breast cancer at days 14 and 42 (respectively) will be compared using separate, two-tailed t-tests, α=0.05.

  3. Differences in the mean size of heat-evoked axon flares between women with breast cancer DURING their initial six weeks of Taxol therapy.

    Time frame: Day 1 (before participant's 1st Taxol infusion), Day 14 (week two of Taxol therapy) and Day 42 (week six of Taxol therapy).

    • Hypothesis (Longitudinal): There WILL be a significant difference in the mean size of heat-evoked axon flares generated on the palmar surface of great toe of women with breast cancer receiving Taxol from (a) day 1 to day 14, (b) day 14 to day 42, and from (c) day 1 to day 42.
    • Differences in the size of heat-evoked axon flares during Taxol therapy will be evaluated using repeated-measures analysis of variance (RM-ANOVA).

  4. Differences in the size of heat-evoked axon flares for healthy women during the six-week study period.

    Time frame: Day 1 (before participant's 1st Taxol infusion), Day 14 (week two of Taxol therapy) and Day 42 (week six of Taxol therapy).

    • Hypothesis (Longitudinal): There WILL NOT be a significant difference in the size of heat-evoked axon flares (in cm2) generated on the great toe of healthy women from (a) day 1 to day 14, (b) day 14 to day 42, and from (c) day 1 to day 42.
    • Differences in the size of heat-evoked axon flares during Taxol therapy will be evaluated using RM-ANOVA.

Other outcomes

  1. Correlations between the size of axon reflexes (expressed in %CVCmax) and the average modified-Total Neuropathy (m-TNS) score for women with breast cancer AT EACH TIMEPOINT during Taxol Therapy.

    Time frame: Day 1 (before participant's 1st Taxol infusion), Day 14 (week two of Taxol therapy) and Day 42 (week six of Taxol therapy).

    • Hypothesis: There WILL BE a statistically significant, inverse correlation between (a) the size of axon reflexes generated on the great toe and (b) the mean total m-TNS scores for women with breast cancer receiving Taxol at Days 1, 14, and 42 (respectively).
    • Note: The 'size of axon reflexes' will be defined using the criteria above. The 'average m-TNS score' will be calculated by averaging the total Modified-Total Neuropathy Score (m-TNS) score (1-20) for each woman with breast cancer, at each time point. Pearson R will be used to determine the magnitude, direction, and statistical significance of bivariate correlations between (a) axon reflex size and (b) average mTNS scores for women with breast cancer receiving Taxol at each study time point.

  2. Correlation between the size of axon reflexes (expressed in %CVCmax) and the average modified Total Neuropathy Score (TNS) for healthy women AT EACH TIMEPOINT during the six-week study period.

    Time frame: Day 1 (before participant's 1st Taxol infusion), Day 14 (week two of Taxol therapy) and Day 42 (week six of Taxol therapy).

    • Hypothesis (Cross-Sectional): There WILL NOT be a significant inverse correlation between the size of axon reflexes generated on the palmar surface of the great toe and healthy women's mean total m-TNS scores at Days 1, 14, and 42 (respectively). (Note: Definitions and analyses are the same as above.)

  3. Correlation between (a) the size of heat-evoked axon flares (in cm2) and (b) the average modified-Total Neuropathy Score (mTNS) for women with breast cancer AT EACH TIMEPOINT during Taxol Therapy.

    Time frame: Day 1 (before participant's 1st Taxol infusion), Day 14 (week two of Taxol therapy) and Day 42 (week six of Taxol therapy).

    • Hypothesis: There WILL be a statistically significant, inverse correlation between (a) the size of heat-evoked axon flares generated on the palmar surface of the great toe and (b) mean total mTNS scores for women with breast cancer receiving weekly Taxol at Days 1, 14, and 42 (respectively).(Note: Definitions and analyses are the same as above.)

  4. Correlation between (a) the size of heat-evoked axon flares (in cm2) and (b) the average modified-Total Neuropathy Score (mTNS) for healthy women AT EACH TIMEPOINT during Taxol Therapy.

    Time frame: Day 1 (before participant's 1st Taxol infusion), Day 14 (week two of Taxol therapy) and Day 42 (week six of Taxol therapy).

    • Hypothesis: There WILL NOT be a statistically significant, inverse correlation between (a) the size of heat-evoked axon flares generated on the palmar surface of the great toe and (2) healthy women's mean total m-TNS scores at Days 1, 14, and 42 (respectively). (Note: Definitions and analyses are the same as above.)

Sponsors and collaborators

Lead sponsor

Indiana University

Other

Collaborators

  • Council for the Advancement of Nursing Science (CANS)
  • Indiana Center for Vascular Biology & Medicine (ICVBM)
  • Midwest Nursing Research Society (MNRS)
  • National Institute of Nursing Research (NINR)

Registry information

Important dates

Study start
2015
Primary completion
2016
Study completion
2016
First posted
Sep 15, 2015
Registry last updated
Oct 27, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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